Saturday, February 26, 2011
Why I Walk
Following is a talk I gave this morning at a NAMI San Diego Walk kick-off event. Our Walk takes place April 16 ...
I walk because I am haunted.
I am haunted by my childhood. By the strange looks from family members, from kids in school. They knew. I knew. Even way back then, I wasn’t normal.
I am haunted by my adulthood. A bright promise denied. They knew. I knew. I’m normal! I wanted to shout.
I’m haunted by what I encounter. A question by a father about his kid who refuses to acknowledge his illness - one I can’t answer. Queries I get from my readers - their loved one is acting strange, very strange. What is wrong? More questions - my doctor won’t listen, my insurance is running out. What the hell is wrong with me?
I’m haunted by a world that doesn’t give a damn. People who are supposed to be helping us who tell us that we have a highly treatable illness that at times is barely treatable, and then turn around and say we should be happy where we are - stuck in a miserable half-life, alone, left to fend for ourselves.
I’m haunted by the fact that everything I read or listen to bears no relation at all to my world, your world. Isn’t anyone paying attention? Doesn’t anyone give a damn?
I’m haunted, you’re haunted. Everyone in this room is haunted. That is why we come out in the rain on a Saturday. That is why we get on the phone. We make noise. That is why we show up at meetings. That is why seven weeks from now, rain or shine, we will show up. We will walk. A family, bound together by experiences that haunt us. We will walk. We will send the world a message.
So much to do, so few of us. A good deal of the time it seems hopeless. But we get involved, anyway. Anyway we can.
No one - absolutely no one - should have to endure one day of what we have been through. Not one day. We will walk.
I will conclude with this:
Back in 2004, when I was newly into my second marriage, I was facilitating a DBSA support group in Princeton, NJ. In walked Kevin, exuding a goofy charm, baseball cap on backward. But there was something about his presence that indicated he was no mere goofball. The others in the room felt it, too.
Over the weeks, I couldn't help but be impressed by the way Kevin carried himself. He would walk up to newcomers and introduce himself and start up a conversation. In the group, he was a great listener, dispensing the wisdom of a sage, leavened by a keen sense of humor.
It was amazing to observe him with people much older. At once, he was deferential, compassionate, and exuding great authority. You simply forgot you were talking to someone much younger. You simply wanted to be around him, laugh with him, seek advice from him. He had his setbacks, his dark moments. Yet, over time - in group, over coffee, over sandwiches, hanging out - I watched him blossom. With his extraordinary people skills, the sky was the limit.
In late 2006, my marriage broke up. Kevin was the first to offer me support. He also reached out to Susan.
Suddenly, I had my life in seven or eight FedEx cartons and a one-way ticket to San Diego. I popped into the DBSA group one last time. Kevin was facilitating. He gave me a heartfelt tribute. I felt the goodness in the man. Goodness, true goodness. That was the last time I saw him alive.
He had so much to live for, so much to offer. Yet, on a miserable muggy New Jersey morning, his brain tricked him into believing otherwise. He was 28. Years later, Susan and I, plus all those he left behind, are still dealing with it.
I've been suicidal. So have most people with this illness. We fully understand, yet - we totally don't understand.
Kevin, you still shine a light on the world. Nothing - nothing - is ever going to extinguish it.
That is why I walk.
***
If you wish to support me in my walk, please go to my NAMI San Diego Walk page.
Thursday, February 24, 2011
Gold Standard Clinical Trials - Opportunity Squandered
We left off with the proposition that for psychiatric purposes “randomized, double-blind, placebo-controlled” (RDPC) clinical trials - medicine’s gold standard - actually tell us nothing. One reason is that we know next to nothing about the phenomenon we’re supposed to be investigating (what the hell is depression, anyway?) which leads to a whole domino effect of faulty assumptions (such as testing “depression” with “antidepressants”).
The other reason has to do with the fact the only ones with the resources to run RDPCs - the drug companies - have marketing objectives in mind, which renders all their findings highly suspect from the outset. I could write a book about the manifold abuses (such as statistical manipulation, data-spinning, ghost-writing, payola to researchers and clinicians) associated with these enterprises. Other people have.
In the real world, if these studies actually told us something, our doctors would have something better to say to us than, “Let’s try Prozac (or Abilify, or whatever) and see how it works.” There would be no endless and frustrating rounds of pill roulette. And maybe there would be less mental illness kicking around.
Ironically, in their over-eager pursuit of “one-size-fits-all” treatments for depression and other common DSM illnesses, Pharma may have missed a golden opportunity to investigate specific things that truly go wrong with us - never mind the illness - where targeted meds treatment may indeed make a huge difference.
I came across my first taste of this at the very first American Psychiatric Association annual meeting I attended in 2002. The conference was stuck in an “antidepressants to treat depression” mindset, and so was I. Then I came across a poster of a very small pilot study (maybe ten patients) by Joseph Goldberg of the Mt Sinai School of Medicine involving treating bipolar depressed patients with Mirapex (pramipexole).
Mirapex, a “dopamine agonist,” is FDA-indicated for treating Parkinson’s. We know what dopamine can do for the brain - just ask any crackhead, tweaker, speed-freak, or anyone who craves a good buzz. But we also know that not enough dopamine equates with being a vegetable - just ask anyone overmedicated on an antipsychotic, which acts as a dopamine-blocker.
To vastly oversimplify, when dopamine is firing right, we have a feeling of being alive. We experience pleasure, our thinking is sharp, we are fully engaged, we look forward to our future. In short, we feel the very opposite to feeling “depressed.”
It’s easy to see where Dr Goldberg was coming from: If we could boot up the dopamine system in the brains of those who would appear to benefit from it, with a med that was safe and non-addictive, we might actually witness a number of patients suddenly coming to life. These type of patients were more likely to be found in the bipolar population, whose depressions tend to manifest as more “anergic” (lack of energy) than those with unipolar depression.
In another words, a depression is not just a depression. The unipolar-bipolar distinction is a very crude one (the DSM doesn’t even bother to make the distinction), but at least this is a move in the right direction.
Pharma already had clinical trials up and running for treating bipolar depression when I was at the 2002 APA, including GSK with Lamictal. Eli Lilly would be out in force the next year with its Prozac-Zyprexa combo Symbyax, and later AstraZeneca would produce two eye-popping results with Seroquel. But there was something different about Dr Goldberg’s approach. In a letter published three years earlier in the American Journal of Psychiatry, he and two colleagues observed:
The greater density of [dopamine] D3 receptors in the mesolimbic areas involved in mood regulation may relate to pramipexole's efficacy in psychomotor-retarded conditions (ie, negative symptoms, Parkinson's disease, depression).
Around the same time, the novel wakefulness agent Provigil (modafinil) came on the scene, FDA-indicated for treating narcolepsy. We didn’t exactly know how the stuff worked, but psychiatry viewed it essentially as “speed with brakes.” Not exactly an amphetamine, but with some effect at booting up dopamine (and possibly also hypocretin, which plays a major role in wakefulness). Could the med be recruited to treat certain types of depression?
Unfortunately, its manufacturer, Cephalon, figured it would be far more efficient to make its case directly to doctors rather than go through the trouble and expense of clinical trials. In 2008, Cephalon pled guilty to a criminal misdemeanor for illegally marketing Provigil and two other meds for off-label uses, and paid a $425 million fine.
Meanwhile, various small studies were proving a clear disincentive for Cephalon to gamble on a major trial. The studies tended to focus on Provigil as an augmenting agent to treat depression, but with no attempt made to single out those patients most likely to respond to an energizing agent. In other words, the failures from treating those who didn’t belong in any of these studies (even if they were “depressed”) masked the successes of those who did (but who were they?).
The Aug 2007 American Journal of Psychiatry published an RDPC study that actually provided a clue. The study followed the approach of Dr Goldberg’s 2002 pilot study that tested Mirapex on a depressed bipolar population, but with Provigil as the dopamine med of choice. The study was funded by the Stanley Medical Research Institute. Cephalon’s involvement was peripheral. The company provided the meds and some supplementary funding.
Eighty-five depressed patients already on bipolar meds (including some on antidepressants) were enrolled in the trial (way less than the 250-500 patients typical of industry-sponsored trials). After six weeks, 44 percent responded (ie depression scores reduced by at least half) vs 23 percent in the placebo group. Nothing to write home about, but clearly a finding that that actually tells us something and demonstrates the potential of RDPCs.
Imagine what we would be able to learn if we were to slice and dice depressed populations in far more sophisticated ways, and run full-scale trials on these various subgroups with both established and novel agents.
Alas, virtually no progress has been made since I stumbled upon Dr Goldberg and his poster way back in 2002.
The other reason has to do with the fact the only ones with the resources to run RDPCs - the drug companies - have marketing objectives in mind, which renders all their findings highly suspect from the outset. I could write a book about the manifold abuses (such as statistical manipulation, data-spinning, ghost-writing, payola to researchers and clinicians) associated with these enterprises. Other people have.
In the real world, if these studies actually told us something, our doctors would have something better to say to us than, “Let’s try Prozac (or Abilify, or whatever) and see how it works.” There would be no endless and frustrating rounds of pill roulette. And maybe there would be less mental illness kicking around.
Ironically, in their over-eager pursuit of “one-size-fits-all” treatments for depression and other common DSM illnesses, Pharma may have missed a golden opportunity to investigate specific things that truly go wrong with us - never mind the illness - where targeted meds treatment may indeed make a huge difference.
I came across my first taste of this at the very first American Psychiatric Association annual meeting I attended in 2002. The conference was stuck in an “antidepressants to treat depression” mindset, and so was I. Then I came across a poster of a very small pilot study (maybe ten patients) by Joseph Goldberg of the Mt Sinai School of Medicine involving treating bipolar depressed patients with Mirapex (pramipexole).
Mirapex, a “dopamine agonist,” is FDA-indicated for treating Parkinson’s. We know what dopamine can do for the brain - just ask any crackhead, tweaker, speed-freak, or anyone who craves a good buzz. But we also know that not enough dopamine equates with being a vegetable - just ask anyone overmedicated on an antipsychotic, which acts as a dopamine-blocker.
To vastly oversimplify, when dopamine is firing right, we have a feeling of being alive. We experience pleasure, our thinking is sharp, we are fully engaged, we look forward to our future. In short, we feel the very opposite to feeling “depressed.”
It’s easy to see where Dr Goldberg was coming from: If we could boot up the dopamine system in the brains of those who would appear to benefit from it, with a med that was safe and non-addictive, we might actually witness a number of patients suddenly coming to life. These type of patients were more likely to be found in the bipolar population, whose depressions tend to manifest as more “anergic” (lack of energy) than those with unipolar depression.
In another words, a depression is not just a depression. The unipolar-bipolar distinction is a very crude one (the DSM doesn’t even bother to make the distinction), but at least this is a move in the right direction.
Pharma already had clinical trials up and running for treating bipolar depression when I was at the 2002 APA, including GSK with Lamictal. Eli Lilly would be out in force the next year with its Prozac-Zyprexa combo Symbyax, and later AstraZeneca would produce two eye-popping results with Seroquel. But there was something different about Dr Goldberg’s approach. In a letter published three years earlier in the American Journal of Psychiatry, he and two colleagues observed:
The greater density of [dopamine] D3 receptors in the mesolimbic areas involved in mood regulation may relate to pramipexole's efficacy in psychomotor-retarded conditions (ie, negative symptoms, Parkinson's disease, depression).
Around the same time, the novel wakefulness agent Provigil (modafinil) came on the scene, FDA-indicated for treating narcolepsy. We didn’t exactly know how the stuff worked, but psychiatry viewed it essentially as “speed with brakes.” Not exactly an amphetamine, but with some effect at booting up dopamine (and possibly also hypocretin, which plays a major role in wakefulness). Could the med be recruited to treat certain types of depression?
Unfortunately, its manufacturer, Cephalon, figured it would be far more efficient to make its case directly to doctors rather than go through the trouble and expense of clinical trials. In 2008, Cephalon pled guilty to a criminal misdemeanor for illegally marketing Provigil and two other meds for off-label uses, and paid a $425 million fine.
Meanwhile, various small studies were proving a clear disincentive for Cephalon to gamble on a major trial. The studies tended to focus on Provigil as an augmenting agent to treat depression, but with no attempt made to single out those patients most likely to respond to an energizing agent. In other words, the failures from treating those who didn’t belong in any of these studies (even if they were “depressed”) masked the successes of those who did (but who were they?).
The Aug 2007 American Journal of Psychiatry published an RDPC study that actually provided a clue. The study followed the approach of Dr Goldberg’s 2002 pilot study that tested Mirapex on a depressed bipolar population, but with Provigil as the dopamine med of choice. The study was funded by the Stanley Medical Research Institute. Cephalon’s involvement was peripheral. The company provided the meds and some supplementary funding.
Eighty-five depressed patients already on bipolar meds (including some on antidepressants) were enrolled in the trial (way less than the 250-500 patients typical of industry-sponsored trials). After six weeks, 44 percent responded (ie depression scores reduced by at least half) vs 23 percent in the placebo group. Nothing to write home about, but clearly a finding that that actually tells us something and demonstrates the potential of RDPCs.
Imagine what we would be able to learn if we were to slice and dice depressed populations in far more sophisticated ways, and run full-scale trials on these various subgroups with both established and novel agents.
Alas, virtually no progress has been made since I stumbled upon Dr Goldberg and his poster way back in 2002.
Labels:
clinical trials,
gold standard,
John McManamy
Wednesday, February 23, 2011
Gold Standard Clinical Trials - Science or Marketing?: Part IV
This is the fifth in a series that takes a hard look at the information that we and our clinicians rely on to give us an insight into our condition and how to treat it. In the first piece, we reviewed three unscientific reader surveys I conducted here at Knowledge is Necessity, rightly at the very bottom of the evidence food chain but that actually told us something. The next three articles (Part I, Part II, Part III) looked at a “randomized, double blind, placebo-controlled” (RDPC) clinical trial that tested J&J's Invega for schizoaffective - regarded as the gold standard of research - but which actually told us nothing.
Moving on ...
In psychiatry, RDPCs imitate science rather than embody science, and therefore need to be regarded with a very high degree of skepticism. Two principles are in play:
What is depression? Feeling sad? Loss of pleasure? Unmotivated? Psychic numbness? Reaction to stress? Loss of energy? Over-ruminating? Under-thinking? On and on, it goes.
In all likelihood, we are talking many - possibly hundreds - of illnesses involving by far the most complex organ in the body and all its related systems, with myriad possible causes and effects (including genetic vulnerability to environmental stressors) recruiting a host of different pathways. RDPCs do not recognize this. Rather they test “antidepressants” on a “depressed” population.
The equivalent would be to treat all infectious diseases as the same, call every such outbreak “runny nose disease,” and run a clinical trial of the same test med on everyone with a runny nose or high fever. Any reasonable bystander would rightly regard this as insane. Why, then, would anyone apply this approach to testing psychiatric meds? Read on ...
Marketing
Only pharmaceutical companies can afford the $40 million or so (my best guess) it takes to conduct the two clinical trials required for an FDA indication to treat an illness, but the pay-off is huge. For a common chronic illness, such as “depression,” an FDA indication amounts to a license to print money.
The drug companies are abetted by the FDA, which sets a very low success threshold for a clinical trial. In the case of antidepressants, assuming safety and tolerability standards are met, a mere 50 percent of those in the drug group need to get merely 50 percent better. (For antipsychotics to test schizophrenia, the standard is even lower.) You can achieve nearly as good a result with a placebo - literally. But why would a drug company care about that? Once they have succeeded in putting a tiny bit of daylight between their drug and the placebo in two trials, they now have their license to print money.
What RDPCs Do Tell Us
Of all things, despite the best efforts by drug companies to produce results favorable to their test med, the one thing clinical trials involving antidepressants do show us is their spectacular lack of effect on wide populations classified as “depressed.” Commentators such as Robert Whitaker have had a field day with this. Likewise Whitaker et al can point to the indisputable fact that these meds have failed to make a dent in the worldwide “depression” epidemic.
There is no way to “refute” or “repudiate” this evidence, except with equally weighty evidence, which does not exist. We can make a case that antidepressants are likely to work extremely well on a certain small subpopulation of patients, but to prove that we would first need to identify this population and then test them in a randomized, double-blind, placebo-controlled clinical trial.
Ironic, isn’t it?
Moving on ...
In psychiatry, RDPCs imitate science rather than embody science, and therefore need to be regarded with a very high degree of skepticism. Two principles are in play:
- We know next to nothing about the phenomenon we are investigating.
- RDPCs are conducted for reasons of marketing.
What is depression? Feeling sad? Loss of pleasure? Unmotivated? Psychic numbness? Reaction to stress? Loss of energy? Over-ruminating? Under-thinking? On and on, it goes.
In all likelihood, we are talking many - possibly hundreds - of illnesses involving by far the most complex organ in the body and all its related systems, with myriad possible causes and effects (including genetic vulnerability to environmental stressors) recruiting a host of different pathways. RDPCs do not recognize this. Rather they test “antidepressants” on a “depressed” population.
The equivalent would be to treat all infectious diseases as the same, call every such outbreak “runny nose disease,” and run a clinical trial of the same test med on everyone with a runny nose or high fever. Any reasonable bystander would rightly regard this as insane. Why, then, would anyone apply this approach to testing psychiatric meds? Read on ...
Marketing
Only pharmaceutical companies can afford the $40 million or so (my best guess) it takes to conduct the two clinical trials required for an FDA indication to treat an illness, but the pay-off is huge. For a common chronic illness, such as “depression,” an FDA indication amounts to a license to print money.
The drug companies are abetted by the FDA, which sets a very low success threshold for a clinical trial. In the case of antidepressants, assuming safety and tolerability standards are met, a mere 50 percent of those in the drug group need to get merely 50 percent better. (For antipsychotics to test schizophrenia, the standard is even lower.) You can achieve nearly as good a result with a placebo - literally. But why would a drug company care about that? Once they have succeeded in putting a tiny bit of daylight between their drug and the placebo in two trials, they now have their license to print money.
What RDPCs Do Tell Us
Of all things, despite the best efforts by drug companies to produce results favorable to their test med, the one thing clinical trials involving antidepressants do show us is their spectacular lack of effect on wide populations classified as “depressed.” Commentators such as Robert Whitaker have had a field day with this. Likewise Whitaker et al can point to the indisputable fact that these meds have failed to make a dent in the worldwide “depression” epidemic.
There is no way to “refute” or “repudiate” this evidence, except with equally weighty evidence, which does not exist. We can make a case that antidepressants are likely to work extremely well on a certain small subpopulation of patients, but to prove that we would first need to identify this population and then test them in a randomized, double-blind, placebo-controlled clinical trial.
Ironic, isn’t it?
Monday, February 21, 2011
Presidents Day Special: Lincoln and His Depressions
I originally published this as a newsletter piece in 2005 and soon after on mcmanweb. Enjoy ...
The year is 1860. In a makeshift meeting hall, the Illinois delegation to the approaching Republican Convention is meeting to consider which of their own to back as a favorite son for the Presidential nomination. There is no clear-cut favorite. Moreover, it’s widely acknowledged the choice will be an empty gesture. The nomination is virtually a done deal. William Seward of New York, the party’s leading light, has nearly all the delegates he needs for a first ballot victory.
But then something completely unexpected happens. Abraham Lincoln is introduced. A distant relation enters carrying two split log rails. From them hangs a banner:
Abraham Lincoln
The Rail Candidate
The crowd goes wild. The hall shakes so much that the canvass roof flies off the building. The image of a humble rail-splitter is all this group of delegates needs to give Lincoln its enthusiastic backing. The dynamics of the nomination has completely changed. Illinois’ freshly-minted favorite son is on his way to becoming a serious contender.
The meeting breaks up the next day. In the nearly empty hall, a man sits alone, elbows bent, hands pressed to his face. He confides to someone who approaches him, "I’m not feeling too well." The man is Abraham Lincoln. He is battling a crushing depression.
The event is recounted in Joshua Shenk’s outstanding 2005 book, "Lincoln’s Melancholy: How Depression Challenged a President and Fueled His Greatness." Writes Mr Shenk:
Lincoln’s look at that moment – the classic image of gloom – was familiar to everyone who knew him well. … He often wept in public and cited maudlin poetry. He told jokes and stories at odd times – he needed the laughs, he said, for his survival. As a young man he talked of suicide, and as he grew older, he said he saw the world as hard and grim, made that way by fates and forces of God. ‘No element of Mr Lincoln’s character,’ declared his colleague Henry Whitney, ‘was so marked, obvious and ingrained as his mysterious and profound melancholy.’ His law partner, William Herndon said, ‘His melancholy dripped from him as he walked.’
Mr Shenk relates that depression was a constant throughout Lincoln’s adult life. He never overcame it. He never rose above it. His life was one long unceasing litany of sorrow. At times, he completely gave in to his condition. He would fail to get out of bed. He would behave very strangely. He would alarm his friends and associates.
"I am now the most miserable man living," the 31-year-old Lincoln confessed. "Whether I shall ever be better I can not tell; I awfully forebode I shall not; To remain as I am is impossible; I must die or be better."
But other forces were also at work, Mr Shenk contends. Depression turned him into a hard-headed realist, untainted by the pitfalls of misguided optimism. His uncanny melancholic third eye allowed him to think like a visionary. And even though he was a religious skeptic, his tribulations would imbue him with a higher wisdom and deeper humanity, so much so that he occupies a unique place in history as an American saint.
It is easy to fall into the trap of romanticizing Lincoln, but the facts speak for themselves. As his life unfolds, one cannot help but have the impression of being in a higher presence. It’s almost a religious experience. Mr Shenk makes the experience all the more moving by allowing us to view the great man through the eyes of our illness. The result is both inspirational and heartbreaking. To begin ….
The Early Years
Abraham Lincoln was different from day one. A voracious reader, intellectually curious, and a sensitive individual in a rural environment that only saw merit in physical labor, the young Lincoln was regarded as lazy and in need of discipline.
There was much cause for sadness in Lincoln’s life. His only brother died in infancy. His mother and aunt and uncle succumbed to an epidemic when he was age nine. Ten years later his sister died giving birth to a still-born infant. His father and mother were disposed to melancholy, and one side of the family "was thick with mental disease."
Despite this, young Lincoln made it into adulthood showing few signs of depression. His first major episode coincided with the death of Anne Rutledge in 1835 when he was 26. Lincoln had long since left the family farm to seek his fortune in the one-horse town of New Salem, Illinois. Many historians contend that there must have been a love interest between Rutledge and Lincoln, but Mr Shenk says there is no evidence.
Depression is not as simple as cause and effect, Mr Shenk reminds us, citing a number of psychiatric sources, especially in someone predisposed to the illness. Any number of apparently innocuous occurrences can set off an episode, including several converging at once. According to one account, Lincoln bore up to Anne’s death fairly well. Then came heavy rains that seemed to unnerve him. He took to walking the woods alone with a gun and talking of suicide. Everyone in the village became aware of his strange behavior, and one concerned couple took him in for a week or two.
Finding His Way in the World
By Lincoln’s late twenties, friends and colleagues regarded him as "melancholic." The condition was virtually indistinguishable from the modern conception of depression, but did not carry the same stigma. Back in those days, despite an individual feeling "unmanned" by his affliction, there was considerable leeway for males to express their feelings in public, especially with the Romantic movement entering full flower.
In Lincoln’s case, his sorrowful demeanor induced people to come to his aid.
Nowhere was this more apparent than when the young man turned up to practice law in Springfield, Illinois with all his worldly possessions in two saddlebags. A store proprietor, Joshua Speed, urged his forlorn customer to take the bags upstairs to his room and the two became fast friends.
In an age when contact with the opposite sex was severely circumscribed, young men were encouraged "to pair off and form a special bond" as part of their grooming for greater responsibilities. Lincoln and Speed even shared the same bed for four years, but this was fairly common practice not to be mistaken for homosexuality. Nevertheless, gender roles were defined quite differently. It was acceptable for young men to display their affection for one another. This kind of intimacy encouraged the expression of one’s innermost thoughts and feelings, including depression.
Mr Shenk points to a number of forces at work when Lincoln was coming of age. On one hand, it was an age of hope. The new economy for the first time gave ambitious young white men like Lincoln the opportunity to realize the dreams of the Founding Fathers. Steam power and the telegraph effectively shrunk the world and created a whole new mobile labor force. Advances in medical science instilled the belief that God was not punishing an individual, which effectively destigmatized illness. This spawned a whole new movement in self-improvement.
At the same time, thanks to a new religious revival, a loving redemptive God replaced the harsh vengeful God of John Calvin. Rather than predestination to hellfire and brimstone, men and women had the power to make moral choices and find their way to God’s favor.
For the first time in history, the individual did not have to subsume his needs to the needs of the tribe or community. But with this new freedom came new fears and anxieties. Gone was the communal security blanket. Ever present was the specter of failure, with full responsibility borne by the exposed individual. America, the land of opportunity, led the world in mental illness.
It was in this heady atmosphere of hope and insecurity that young Lincoln, now a hotshot lawyer and rising star in the state legislature, was to become badly unhinged.
Lincoln's Breakdown
Many historians attribute Lincoln’s depressive episode of the winter of 1840-41 to his breaking off his engagement with Mary Todd. But much more was happening in Lincoln’s life, Mr Shenk points out.
In the legislature, Lincoln had hitched his political wagon to ambitious public works projects designed to open up the hinterlands to economic development. This included an elaborate network of rails, canals, and roads.
Then came the economic depression of 1837. Revenues dried up and the debt exploded. Lincoln used up all his political capital urging the legislature to stay the course, which proved a disaster. By the end of 1840, the state was teetering on the brink of bankruptcy, forcing the abandonment of Lincoln’s beloved projects. The rival Democrats rode into power on the aftermath of the debacle, and Lincoln was cast as one of the scapegoats. He barely held onto his seat in the legislature, his political career virtually finished.
At the same time, he was laboring under a heavy workload as a lawyer, with nine cases before the state supreme court.
As for Mary Todd, the exact time of the break-up is unknown, obviating a simple cause and effect. Another woman had turned him down, and he may have had an interest in yet another. On top of this, his dear friend Joshua Speed was making plans to move back to Kentucky. Then the weather turned bitterly cold.
In January 1841, Lincoln was confined to his bed, and his condition was the talk of the town. He put himself in the care of a physician, which likely made him much worse. Standard medical treatment involved purging the body by aggressively drawing blood, ingesting mercury and other poisons, inducing vomiting, starving the patient, and plunging him in cold water.
A concerned Joshua Speed told Lincoln that if he did not rally he would die. Lincoln replied he was not afraid to die. Yet, ironically, his perceived failures may have stoked his will to live. He confessed to his friend an "irrepressible desire" to accomplish something before he died that would "redound to the interest of his fellow man."
Some 20 years later, Lincoln would remind his friend of that conversation.
Finding Himself
In late 1842, Lincoln bit the bullet and married Mary Todd. His way of dealing with his depression was by throwing himself into his family and his work, but it wasn’t until he reached his mid-forties that he found a cause that animated him. The Missouri Compromise of 1820 had regulated the extension of slavery in the western territories. In practice, it operated as a containment policy that implicitly recognized slavery’s wrong. Lincoln foresaw slavery’s eventual end, but it was not a process, he believed, that could be speeded up.
That all changed in 1854 with the passage of the Kansas-Nebraska Act. Suddenly the northern territories were in play. Three years later, the Supreme Court’s infamous Dred Scott decision held out the prospect of legalized slavery in the northern states, as well. Slavery was no longer a wrong. It was about to become a universally recognized right. Passions on both sides were awakened, but the situation clearly favored the south.
Lincoln’s melancholia allowed him to see events with preternatural second sight. Southerners with a vested interest in the outcome stood a clear chance of having their way over largely indifferent northerners. It was the thin edge of the wedge that could put an end to free labor markets everywhere and dash the dreams of the Founding Fathers. The clock was being rewound back to the Dark Ages, and Lincoln was not confident of his ability to put a stop to it. Nevertheless, he felt compelled to speak out against the madness, even at the risk of his career.
Paradoxically, his political career took off, though true to melancholic form he saw every slight setback as a major failure. The new political reality spelled the end of Lincoln’s Whig party. In its place stood the newly-formed Republican party. In 1858, Lincoln found himself in the national spotlight in his series of debates with the author of the Kansas-Nebraska Act, Stephen Douglas. Both were contesting the same Senate seat.
The Senate was Lincoln’s lifelong dream. In an era of lackluster Presidents, this was the forum of his heroes such as Daniel Webster and Henry Clay. But Lincoln was prepared to sacrifice his ambitions for the cause. His antislavery position ran ahead of public opinion, but he strongly felt the greater interest was better served by enlightening the voters.
Lincoln also saw ahead to 1860, when Douglas was likely to be the Democratic standard-bearer in the Presidential election. In the debates, he forced his rival to expose himself as too moderate for his southern backers. The next Republican candidate for President, he knew – certainly not he – would benefit.
Lest we mistake Lincoln as morally flawless, he neither viewed African-Americans as biologically equal to whites nor did he envision the two races living together in harmony. The world was a stupid place back then, arguably only slightly more stupid than it is today.
In early 1860, Lincoln traveled to New York to deliver an address to the Cooper Institute. He brilliantly succeeded in linking the dreams of the Founding Fathers to the anti-slavery position, and threw down the gauntlet on right versus wrong. He brought down the house, and achieved rave notices everywhere. No one was quite ready to seriously consider him as Presidential timber. Yet …
Improbably, on the strength of his new-found image as the rail-splitter, Lincoln won his party’s nomination on the third ballot. The election was a shoo-in. Thanks in part to the Lincoln-Douglas debates from two years before, an irreparable schism had formed in the pro-slavery ranks. The Democratic party splintered three ways, allowing Lincoln to win with just 40 percent of the popular vote.
Even more improbable, Lincoln’s well-known melancholia was not seen as a character flaw. Today, the immensity of a Lincoln-sized depression would disqualify a candidate from virtually any elected office save dog-catcher. Back in Lincoln’s time, living successfully with a mental illness was viewed as a character virtue. Maybe they weren’t all that stupid back then, after all.
The Presidency
By the time Lincoln was sworn in, seven southern states had bolted from the Union. Facing the Republic’s gravest crisis, he assumed office with no executive experience, forced to govern from an untenable position. One slight overstep and the border states would join the South, ending all hope of reunification. When hostilities broke out, the North lost far more battles than it won, forcing all and sundry to second-guess his leadership. As the terrible carnage mounted, much of the population lost its resolve, leaving Lincoln with a very weak bargaining hand. When he pressed his position harder, rebellion threatened to erupt on the home front. Few believed there would be a successful conclusion to the war. No one thought he could be reelected.
Of all things, a lifetime of living with depression admirably prepared him for the task. He possessed both the intestinal fortitude and the moral will. And the insights he had acquired from a lifetime of sorrow seemed to connect him to a higher power. As Joshua Shenk explains, over the course of his adulthood, Lincoln passed from fear to engagement to transcendence.
In other words, having decided that he WOULD live, he then decided HOW to live. When faced with the challenge of a lifetime, he proved more than ready.
But first came more personal tragedy. During his term of office, His favorite son, Willie, died. Of his four sons, only one would live to adulthood. On learning of the death of Willie, he wept convulsively.
In 1862, Lincoln deviated from a previously-held position by proposing to his cabinet the emancipation of slaves from all union-held southern territory. The move risked alienating the border states, but would serve to give the war a higher moral purpose. Nevertheless, Lincoln entertained no delusions about whose side God was on. Death had visited far too many northern households for him to believe that the Almighty was playing favorites. "My greatest concern is to be on God's side," he advised a colleague.
The Emancipation Proclamation would be the first step toward universal freedom and enfranchisement. Soon after, Joshua Speed would pay a visit, and Lincoln would remind him of their conversation some twenty years earlier, when only his desire to accomplish something great gave him the will to live.
"I believe in this measure my fondest hopes will be realized," he confided to his friend.
Sainthood
On assuming his second term of office, Lincoln spoke the finest words ever uttered in the English tongue:
With malice toward none, with charity for all, with firmness in the right, as God gives us to see the right, let us strive on to finish the work we are in, to bind up the nation's wounds.
He had six weeks to live, his last days filled with a transcendent lightness of being. It was as if, his mission on earth accomplished, he were ready to be taken up into heaven. On April 14, 1865, a man with a gun obliged. Now he belonged to the ages.
Final Words
In Lincoln’s depressions, we see the illness in its full destructive horror, one that nearly succeeded in cutting short the life of a promising young man and made the rest of his existence miserable. This is the side of depression with which we can all unfortunately identify. But we also see an aspect to his depressions that equally resonates with us – how our suffering can strengthen us, ennoble us, and embolden us, often to achieve the impossible.
Our sense of achievement need not be the same as Lincoln’s, nor for that matter what our families may expect of us. It is simply enough that we survive from day to day with the kind of grace that is used to define courage. Believe me, if Lincoln were to visit you right now, he might admonish you to make your bed, but he would do it in the way of a funny story. And he would let you know how proud is of you - no doubt about it. Take heart. Lincoln lives in us all. Walk tall.
The year is 1860. In a makeshift meeting hall, the Illinois delegation to the approaching Republican Convention is meeting to consider which of their own to back as a favorite son for the Presidential nomination. There is no clear-cut favorite. Moreover, it’s widely acknowledged the choice will be an empty gesture. The nomination is virtually a done deal. William Seward of New York, the party’s leading light, has nearly all the delegates he needs for a first ballot victory.
But then something completely unexpected happens. Abraham Lincoln is introduced. A distant relation enters carrying two split log rails. From them hangs a banner:
Abraham Lincoln
The Rail Candidate
The crowd goes wild. The hall shakes so much that the canvass roof flies off the building. The image of a humble rail-splitter is all this group of delegates needs to give Lincoln its enthusiastic backing. The dynamics of the nomination has completely changed. Illinois’ freshly-minted favorite son is on his way to becoming a serious contender.
The meeting breaks up the next day. In the nearly empty hall, a man sits alone, elbows bent, hands pressed to his face. He confides to someone who approaches him, "I’m not feeling too well." The man is Abraham Lincoln. He is battling a crushing depression.
The event is recounted in Joshua Shenk’s outstanding 2005 book, "Lincoln’s Melancholy: How Depression Challenged a President and Fueled His Greatness." Writes Mr Shenk:
Lincoln’s look at that moment – the classic image of gloom – was familiar to everyone who knew him well. … He often wept in public and cited maudlin poetry. He told jokes and stories at odd times – he needed the laughs, he said, for his survival. As a young man he talked of suicide, and as he grew older, he said he saw the world as hard and grim, made that way by fates and forces of God. ‘No element of Mr Lincoln’s character,’ declared his colleague Henry Whitney, ‘was so marked, obvious and ingrained as his mysterious and profound melancholy.’ His law partner, William Herndon said, ‘His melancholy dripped from him as he walked.’
Mr Shenk relates that depression was a constant throughout Lincoln’s adult life. He never overcame it. He never rose above it. His life was one long unceasing litany of sorrow. At times, he completely gave in to his condition. He would fail to get out of bed. He would behave very strangely. He would alarm his friends and associates.
"I am now the most miserable man living," the 31-year-old Lincoln confessed. "Whether I shall ever be better I can not tell; I awfully forebode I shall not; To remain as I am is impossible; I must die or be better."
But other forces were also at work, Mr Shenk contends. Depression turned him into a hard-headed realist, untainted by the pitfalls of misguided optimism. His uncanny melancholic third eye allowed him to think like a visionary. And even though he was a religious skeptic, his tribulations would imbue him with a higher wisdom and deeper humanity, so much so that he occupies a unique place in history as an American saint.
It is easy to fall into the trap of romanticizing Lincoln, but the facts speak for themselves. As his life unfolds, one cannot help but have the impression of being in a higher presence. It’s almost a religious experience. Mr Shenk makes the experience all the more moving by allowing us to view the great man through the eyes of our illness. The result is both inspirational and heartbreaking. To begin ….
The Early Years
Abraham Lincoln was different from day one. A voracious reader, intellectually curious, and a sensitive individual in a rural environment that only saw merit in physical labor, the young Lincoln was regarded as lazy and in need of discipline.
There was much cause for sadness in Lincoln’s life. His only brother died in infancy. His mother and aunt and uncle succumbed to an epidemic when he was age nine. Ten years later his sister died giving birth to a still-born infant. His father and mother were disposed to melancholy, and one side of the family "was thick with mental disease."
Despite this, young Lincoln made it into adulthood showing few signs of depression. His first major episode coincided with the death of Anne Rutledge in 1835 when he was 26. Lincoln had long since left the family farm to seek his fortune in the one-horse town of New Salem, Illinois. Many historians contend that there must have been a love interest between Rutledge and Lincoln, but Mr Shenk says there is no evidence.
Depression is not as simple as cause and effect, Mr Shenk reminds us, citing a number of psychiatric sources, especially in someone predisposed to the illness. Any number of apparently innocuous occurrences can set off an episode, including several converging at once. According to one account, Lincoln bore up to Anne’s death fairly well. Then came heavy rains that seemed to unnerve him. He took to walking the woods alone with a gun and talking of suicide. Everyone in the village became aware of his strange behavior, and one concerned couple took him in for a week or two.
Finding His Way in the World
By Lincoln’s late twenties, friends and colleagues regarded him as "melancholic." The condition was virtually indistinguishable from the modern conception of depression, but did not carry the same stigma. Back in those days, despite an individual feeling "unmanned" by his affliction, there was considerable leeway for males to express their feelings in public, especially with the Romantic movement entering full flower.
In Lincoln’s case, his sorrowful demeanor induced people to come to his aid.
Nowhere was this more apparent than when the young man turned up to practice law in Springfield, Illinois with all his worldly possessions in two saddlebags. A store proprietor, Joshua Speed, urged his forlorn customer to take the bags upstairs to his room and the two became fast friends.
In an age when contact with the opposite sex was severely circumscribed, young men were encouraged "to pair off and form a special bond" as part of their grooming for greater responsibilities. Lincoln and Speed even shared the same bed for four years, but this was fairly common practice not to be mistaken for homosexuality. Nevertheless, gender roles were defined quite differently. It was acceptable for young men to display their affection for one another. This kind of intimacy encouraged the expression of one’s innermost thoughts and feelings, including depression.
Mr Shenk points to a number of forces at work when Lincoln was coming of age. On one hand, it was an age of hope. The new economy for the first time gave ambitious young white men like Lincoln the opportunity to realize the dreams of the Founding Fathers. Steam power and the telegraph effectively shrunk the world and created a whole new mobile labor force. Advances in medical science instilled the belief that God was not punishing an individual, which effectively destigmatized illness. This spawned a whole new movement in self-improvement.
At the same time, thanks to a new religious revival, a loving redemptive God replaced the harsh vengeful God of John Calvin. Rather than predestination to hellfire and brimstone, men and women had the power to make moral choices and find their way to God’s favor.
For the first time in history, the individual did not have to subsume his needs to the needs of the tribe or community. But with this new freedom came new fears and anxieties. Gone was the communal security blanket. Ever present was the specter of failure, with full responsibility borne by the exposed individual. America, the land of opportunity, led the world in mental illness.
It was in this heady atmosphere of hope and insecurity that young Lincoln, now a hotshot lawyer and rising star in the state legislature, was to become badly unhinged.
Lincoln's Breakdown
Many historians attribute Lincoln’s depressive episode of the winter of 1840-41 to his breaking off his engagement with Mary Todd. But much more was happening in Lincoln’s life, Mr Shenk points out.
In the legislature, Lincoln had hitched his political wagon to ambitious public works projects designed to open up the hinterlands to economic development. This included an elaborate network of rails, canals, and roads.
Then came the economic depression of 1837. Revenues dried up and the debt exploded. Lincoln used up all his political capital urging the legislature to stay the course, which proved a disaster. By the end of 1840, the state was teetering on the brink of bankruptcy, forcing the abandonment of Lincoln’s beloved projects. The rival Democrats rode into power on the aftermath of the debacle, and Lincoln was cast as one of the scapegoats. He barely held onto his seat in the legislature, his political career virtually finished.
At the same time, he was laboring under a heavy workload as a lawyer, with nine cases before the state supreme court.
As for Mary Todd, the exact time of the break-up is unknown, obviating a simple cause and effect. Another woman had turned him down, and he may have had an interest in yet another. On top of this, his dear friend Joshua Speed was making plans to move back to Kentucky. Then the weather turned bitterly cold.
In January 1841, Lincoln was confined to his bed, and his condition was the talk of the town. He put himself in the care of a physician, which likely made him much worse. Standard medical treatment involved purging the body by aggressively drawing blood, ingesting mercury and other poisons, inducing vomiting, starving the patient, and plunging him in cold water.
A concerned Joshua Speed told Lincoln that if he did not rally he would die. Lincoln replied he was not afraid to die. Yet, ironically, his perceived failures may have stoked his will to live. He confessed to his friend an "irrepressible desire" to accomplish something before he died that would "redound to the interest of his fellow man."
Some 20 years later, Lincoln would remind his friend of that conversation.
Finding Himself
In late 1842, Lincoln bit the bullet and married Mary Todd. His way of dealing with his depression was by throwing himself into his family and his work, but it wasn’t until he reached his mid-forties that he found a cause that animated him. The Missouri Compromise of 1820 had regulated the extension of slavery in the western territories. In practice, it operated as a containment policy that implicitly recognized slavery’s wrong. Lincoln foresaw slavery’s eventual end, but it was not a process, he believed, that could be speeded up.
That all changed in 1854 with the passage of the Kansas-Nebraska Act. Suddenly the northern territories were in play. Three years later, the Supreme Court’s infamous Dred Scott decision held out the prospect of legalized slavery in the northern states, as well. Slavery was no longer a wrong. It was about to become a universally recognized right. Passions on both sides were awakened, but the situation clearly favored the south.
Lincoln’s melancholia allowed him to see events with preternatural second sight. Southerners with a vested interest in the outcome stood a clear chance of having their way over largely indifferent northerners. It was the thin edge of the wedge that could put an end to free labor markets everywhere and dash the dreams of the Founding Fathers. The clock was being rewound back to the Dark Ages, and Lincoln was not confident of his ability to put a stop to it. Nevertheless, he felt compelled to speak out against the madness, even at the risk of his career.
Paradoxically, his political career took off, though true to melancholic form he saw every slight setback as a major failure. The new political reality spelled the end of Lincoln’s Whig party. In its place stood the newly-formed Republican party. In 1858, Lincoln found himself in the national spotlight in his series of debates with the author of the Kansas-Nebraska Act, Stephen Douglas. Both were contesting the same Senate seat.
The Senate was Lincoln’s lifelong dream. In an era of lackluster Presidents, this was the forum of his heroes such as Daniel Webster and Henry Clay. But Lincoln was prepared to sacrifice his ambitions for the cause. His antislavery position ran ahead of public opinion, but he strongly felt the greater interest was better served by enlightening the voters.
Lincoln also saw ahead to 1860, when Douglas was likely to be the Democratic standard-bearer in the Presidential election. In the debates, he forced his rival to expose himself as too moderate for his southern backers. The next Republican candidate for President, he knew – certainly not he – would benefit.
Lest we mistake Lincoln as morally flawless, he neither viewed African-Americans as biologically equal to whites nor did he envision the two races living together in harmony. The world was a stupid place back then, arguably only slightly more stupid than it is today.
In early 1860, Lincoln traveled to New York to deliver an address to the Cooper Institute. He brilliantly succeeded in linking the dreams of the Founding Fathers to the anti-slavery position, and threw down the gauntlet on right versus wrong. He brought down the house, and achieved rave notices everywhere. No one was quite ready to seriously consider him as Presidential timber. Yet …
Improbably, on the strength of his new-found image as the rail-splitter, Lincoln won his party’s nomination on the third ballot. The election was a shoo-in. Thanks in part to the Lincoln-Douglas debates from two years before, an irreparable schism had formed in the pro-slavery ranks. The Democratic party splintered three ways, allowing Lincoln to win with just 40 percent of the popular vote.
Even more improbable, Lincoln’s well-known melancholia was not seen as a character flaw. Today, the immensity of a Lincoln-sized depression would disqualify a candidate from virtually any elected office save dog-catcher. Back in Lincoln’s time, living successfully with a mental illness was viewed as a character virtue. Maybe they weren’t all that stupid back then, after all.
The Presidency
By the time Lincoln was sworn in, seven southern states had bolted from the Union. Facing the Republic’s gravest crisis, he assumed office with no executive experience, forced to govern from an untenable position. One slight overstep and the border states would join the South, ending all hope of reunification. When hostilities broke out, the North lost far more battles than it won, forcing all and sundry to second-guess his leadership. As the terrible carnage mounted, much of the population lost its resolve, leaving Lincoln with a very weak bargaining hand. When he pressed his position harder, rebellion threatened to erupt on the home front. Few believed there would be a successful conclusion to the war. No one thought he could be reelected.
Of all things, a lifetime of living with depression admirably prepared him for the task. He possessed both the intestinal fortitude and the moral will. And the insights he had acquired from a lifetime of sorrow seemed to connect him to a higher power. As Joshua Shenk explains, over the course of his adulthood, Lincoln passed from fear to engagement to transcendence.
In other words, having decided that he WOULD live, he then decided HOW to live. When faced with the challenge of a lifetime, he proved more than ready.
But first came more personal tragedy. During his term of office, His favorite son, Willie, died. Of his four sons, only one would live to adulthood. On learning of the death of Willie, he wept convulsively.
In 1862, Lincoln deviated from a previously-held position by proposing to his cabinet the emancipation of slaves from all union-held southern territory. The move risked alienating the border states, but would serve to give the war a higher moral purpose. Nevertheless, Lincoln entertained no delusions about whose side God was on. Death had visited far too many northern households for him to believe that the Almighty was playing favorites. "My greatest concern is to be on God's side," he advised a colleague.
The Emancipation Proclamation would be the first step toward universal freedom and enfranchisement. Soon after, Joshua Speed would pay a visit, and Lincoln would remind him of their conversation some twenty years earlier, when only his desire to accomplish something great gave him the will to live.
"I believe in this measure my fondest hopes will be realized," he confided to his friend.
Sainthood
On assuming his second term of office, Lincoln spoke the finest words ever uttered in the English tongue:
With malice toward none, with charity for all, with firmness in the right, as God gives us to see the right, let us strive on to finish the work we are in, to bind up the nation's wounds.
He had six weeks to live, his last days filled with a transcendent lightness of being. It was as if, his mission on earth accomplished, he were ready to be taken up into heaven. On April 14, 1865, a man with a gun obliged. Now he belonged to the ages.
Final Words
In Lincoln’s depressions, we see the illness in its full destructive horror, one that nearly succeeded in cutting short the life of a promising young man and made the rest of his existence miserable. This is the side of depression with which we can all unfortunately identify. But we also see an aspect to his depressions that equally resonates with us – how our suffering can strengthen us, ennoble us, and embolden us, often to achieve the impossible.
Our sense of achievement need not be the same as Lincoln’s, nor for that matter what our families may expect of us. It is simply enough that we survive from day to day with the kind of grace that is used to define courage. Believe me, if Lincoln were to visit you right now, he might admonish you to make your bed, but he would do it in the way of a funny story. And he would let you know how proud is of you - no doubt about it. Take heart. Lincoln lives in us all. Walk tall.
Friday, February 18, 2011
Never Mind Our Illness - What About the Real Stuff?
The following originally appeared as two unconnected blog posts in 2009. Last month, I connected them into a new article on mcmanweb ...
"What is holding you back most in your recovery?" I asked readers at Knowledge is Necessity in March 2009. Readers were free to check off as many of the nine answers as they wished. (169 respondents accounted for 490 answers, averaging 2.9 answers per person.) You could have knocked me over with a feather with the results:
Only 35 percent of those who responded checked off, "Unresolved illness symptoms." In other words, a full 65 percent felt that their illness no longer posed an obstacle to their recovery.
Does this mean psychiatry has a high success rate? Um ... not exactly. In a survey from two months before, only 14 percent told me they "were back to where [they] wanted to be or better than [they] ever could have imagined."
What is going on here? Could it be that we have other stuff we need to deal with? This is where it gets interesting.
Interpersonal Relationships
Fifty percent (representing by far the largest total) responded that the thing holding them back the most was "fears/difficulties in dealing with people." Very closely related (at 35 percent) was a "bad living/work/etc" situation.
Clearly, we have major interpersonal issues that need addressing. Without doubt, our respective illnesses play havoc with our ability to get along with people. But my readers seemed to be telling me was that people problems have taken on a life of their own, and it's not hard to imagine why.
Often, we can't go back to our old relationships or work. As we become isolated and cut off, our social skills atrophy. We lose confidence. We are overwhelmed.
In essence, half of those who responded to my survey are telling me that they see the world as a threatening and hostile place, and this does not bode well for recovery. We tend to judge personal success by how well we get along with others. Unfortunately, there is no magic pill to help us. But there exists a lot of therapeutic and social help. You - yes, you - have identified this issue as your top priority. Please do not hesitate to act.
Fears and Anxiety
Also related to this (at 32 percent, one in three) is "inability to manage fears, impulses, etc apparently unrelated to your illness." Maybe you don't attribute, say, anger, to your illness. Maybe you talk too much or are afraid to speak up. Maybe going with an irrational thought makes you feel good. These are common problems that the general population also experiences, but you have added this twist - your sense of lack of control is holding as many of you back in your recovery as unresolved illness symptoms.
Your clinician may have overlooked all this, but clearly you haven't. You know what you need to do.
Bad Habits, Side Effects, Addictions, Ailments
We all have "bad personal habits" (even those with good personal habits), but 36 percent felt these were impeding their progress. Likewise, 30 percent reported that "making excuses" constitutes a major problem.
Overcoming bad habits, of course, falls into the same category as keeping New Year's resolutions. Good luck - you have your work cut out for you.
Finally: Meds side effects (24 percent), addictions (21 percent), and physical ailments (21 percent).
Tying This Into a Bow
There is no such thing as "just depression," "just bipolar," "just anxiety," and so on. A lot of other stuff is going on. Whether wrapped in your illness or independent of it, it all needs to be addressed, because if it isn't - recovery is simply not going to happen
A Reader Weighs In
Louise commented that "many, many people do not want full recovery because it would force them to take full responsibility for their lives and relinquish the power of being 'needy.'"
It happens a lot in physical illnesses, she was quick to add, patients who refuse to follow doctor's orders. For instance:
In the case of my friend's mother, she actually refuses to drink WATER. She wants alcohol and coffee, saying they "taste" better. She is in RENAL FAILURE. She is also a total "victim" control freak making her adult kids jump for every crisis - which she creates.
We all work hard to support and encourage our less-healthy loved ones to recover and live "full" lives again. But what if they don't really want to?
As for those with mental illness: "Some may say people with mental illnesses are not really making this 'choice.' But I can attest that many people with no strong mental illness problems DO make this choice everyday."
Louise was talking about willful disobedience rather than willpower, which other readers brought up. Hold that thought ...
In the meantime, Louise's comments got me thinking:
I certainly did not wish to stay sick, but I do acknowledge that being sick conferred on me a certain degree of absolution. Instead of regarding myself as an underachieving screw-up - in my own mind anyway - I could view myself as someone who overcame tremendous odds.
For the first time in my life, I actually gave myself a pat on the back.
But this came at the price of seeing myself as my illness, rather than seeing myself as me. Which meant I was encouraging people close to me to see me to also see me as my illness. Seeing myself as my illness worked for me for a little while. It gave me a fresh start. It allowed me to take stock. But once I got my illness under control, there was the small matter of working on the stuff that was really holding me back. The real work was only just beginning.
Dean Ornish Weighs In
Two months after my reader poll, I was in San Francisco, at the American Psychiatric Association annual meeting. There I heard celebrity doctor Dean Ornish of UCSF talk about smart lifestyle. For instance, in a 1998 study published in JAMA, Dr Ornish found that patients can not only stop the progression of heart disease through lifestyle management, but can actually reverse it.
In fact, smart lifestyle reliably works across a range of illnesses (including depression), and can often replace invasive and costly treatment (or at least make the treatment work better). The catch is you have to do it, and therein lies the problem. "What's sustainable," Dr Ornish said, "is not fear of dying but joy of living."
Dr Ornish is no stranger to depression, having experienced a severe episode that sidelined him from college. Loneliness and isolation, he said, increases mortality 3.7 times. Depressed individuals are more likely to over-eat, smoke, drink, and work too hard.
You would think that making a few simple changes would be easy, right?
"'Dean, you don't get it,'" his patients told him. "'These behaviors get us through the day.'"
Getting through the day anyway they could was more important to them than living to age 86. In essence, these people could see no benefit to giving up smoking if it meant losing their cigarette-smoking friends, especially if there was nothing to replace those friends.
Meanwhile, the research on the benefits of positive lifestyle kept mounting up. In one 2008 study published in PLoS (JA Dusek lead author), researchers found that the relaxation response in trained meditators switched off cancer-promoting genes.
Changing our lifestyle actually changes our genes, Dr Ornish pointed out. But who wants to change their lifestyle? What Dr Ornish finally figured out was that will power was a nonstarter for individuals, as was the motivation to live longer. "Who wants to live long if you're depressed?" he asked.
What works, he said, is joy, pleasure, freedom. Up went a slide of two tango-dancers - Dr Ornish and his wife. Doing the tango was part of Dr Ornish's exercise routine.
That's when the lightbulb went off: Yes, we need to lead disciplined lives, but we are doomed to failure unless we incorporate fun into our routines. Here, in this Recovery section, are numerous articles about the virtues of good diet, exercise, yoga, meditation, and so on. We know all this stuff works, but what good is any of it if we give up?
Then it occurred to me: None of my lifestyle routines are based on iron will. They all have enjoyment incorporated into them. For instance, my "exercise" is daily walks, water volleyball, and (off and on) dancing. My "diet" is based on my love of cooking, where anything I throw together is both tastier and healthier than restaurant food. My "stress-management" is all about building contemplative time-outs into my schedule. Even my "meditation" has a fun twist - I play the didgeridoo.
In the words of Dr Ornish: "Doing the tango makes your brain grow ... Some of the things that are most fun are good for you."
Glad I thought of it.
***
My previous three pieces reviewed a randomized, double blind, placebo-controlled clinical trial - representing the gold standard of scientific research - that told us nothing. My humble little reader poll, on the other hand, does not even meet the lowest standards of research. But I ask you: Did it tell you something?
"What is holding you back most in your recovery?" I asked readers at Knowledge is Necessity in March 2009. Readers were free to check off as many of the nine answers as they wished. (169 respondents accounted for 490 answers, averaging 2.9 answers per person.) You could have knocked me over with a feather with the results:
Only 35 percent of those who responded checked off, "Unresolved illness symptoms." In other words, a full 65 percent felt that their illness no longer posed an obstacle to their recovery.
Does this mean psychiatry has a high success rate? Um ... not exactly. In a survey from two months before, only 14 percent told me they "were back to where [they] wanted to be or better than [they] ever could have imagined."
What is going on here? Could it be that we have other stuff we need to deal with? This is where it gets interesting.
Interpersonal Relationships
Fifty percent (representing by far the largest total) responded that the thing holding them back the most was "fears/difficulties in dealing with people." Very closely related (at 35 percent) was a "bad living/work/etc" situation.
Clearly, we have major interpersonal issues that need addressing. Without doubt, our respective illnesses play havoc with our ability to get along with people. But my readers seemed to be telling me was that people problems have taken on a life of their own, and it's not hard to imagine why.
Often, we can't go back to our old relationships or work. As we become isolated and cut off, our social skills atrophy. We lose confidence. We are overwhelmed.
In essence, half of those who responded to my survey are telling me that they see the world as a threatening and hostile place, and this does not bode well for recovery. We tend to judge personal success by how well we get along with others. Unfortunately, there is no magic pill to help us. But there exists a lot of therapeutic and social help. You - yes, you - have identified this issue as your top priority. Please do not hesitate to act.
Fears and Anxiety
Also related to this (at 32 percent, one in three) is "inability to manage fears, impulses, etc apparently unrelated to your illness." Maybe you don't attribute, say, anger, to your illness. Maybe you talk too much or are afraid to speak up. Maybe going with an irrational thought makes you feel good. These are common problems that the general population also experiences, but you have added this twist - your sense of lack of control is holding as many of you back in your recovery as unresolved illness symptoms.
Your clinician may have overlooked all this, but clearly you haven't. You know what you need to do.
Bad Habits, Side Effects, Addictions, Ailments
We all have "bad personal habits" (even those with good personal habits), but 36 percent felt these were impeding their progress. Likewise, 30 percent reported that "making excuses" constitutes a major problem.
Overcoming bad habits, of course, falls into the same category as keeping New Year's resolutions. Good luck - you have your work cut out for you.
Finally: Meds side effects (24 percent), addictions (21 percent), and physical ailments (21 percent).
Tying This Into a Bow
There is no such thing as "just depression," "just bipolar," "just anxiety," and so on. A lot of other stuff is going on. Whether wrapped in your illness or independent of it, it all needs to be addressed, because if it isn't - recovery is simply not going to happen
A Reader Weighs In
Louise commented that "many, many people do not want full recovery because it would force them to take full responsibility for their lives and relinquish the power of being 'needy.'"
It happens a lot in physical illnesses, she was quick to add, patients who refuse to follow doctor's orders. For instance:
In the case of my friend's mother, she actually refuses to drink WATER. She wants alcohol and coffee, saying they "taste" better. She is in RENAL FAILURE. She is also a total "victim" control freak making her adult kids jump for every crisis - which she creates.
We all work hard to support and encourage our less-healthy loved ones to recover and live "full" lives again. But what if they don't really want to?
As for those with mental illness: "Some may say people with mental illnesses are not really making this 'choice.' But I can attest that many people with no strong mental illness problems DO make this choice everyday."
Louise was talking about willful disobedience rather than willpower, which other readers brought up. Hold that thought ...
In the meantime, Louise's comments got me thinking:
I certainly did not wish to stay sick, but I do acknowledge that being sick conferred on me a certain degree of absolution. Instead of regarding myself as an underachieving screw-up - in my own mind anyway - I could view myself as someone who overcame tremendous odds.
For the first time in my life, I actually gave myself a pat on the back.
But this came at the price of seeing myself as my illness, rather than seeing myself as me. Which meant I was encouraging people close to me to see me to also see me as my illness. Seeing myself as my illness worked for me for a little while. It gave me a fresh start. It allowed me to take stock. But once I got my illness under control, there was the small matter of working on the stuff that was really holding me back. The real work was only just beginning.
Dean Ornish Weighs In
Two months after my reader poll, I was in San Francisco, at the American Psychiatric Association annual meeting. There I heard celebrity doctor Dean Ornish of UCSF talk about smart lifestyle. For instance, in a 1998 study published in JAMA, Dr Ornish found that patients can not only stop the progression of heart disease through lifestyle management, but can actually reverse it.
In fact, smart lifestyle reliably works across a range of illnesses (including depression), and can often replace invasive and costly treatment (or at least make the treatment work better). The catch is you have to do it, and therein lies the problem. "What's sustainable," Dr Ornish said, "is not fear of dying but joy of living."
Dr Ornish is no stranger to depression, having experienced a severe episode that sidelined him from college. Loneliness and isolation, he said, increases mortality 3.7 times. Depressed individuals are more likely to over-eat, smoke, drink, and work too hard.
You would think that making a few simple changes would be easy, right?
"'Dean, you don't get it,'" his patients told him. "'These behaviors get us through the day.'"
Getting through the day anyway they could was more important to them than living to age 86. In essence, these people could see no benefit to giving up smoking if it meant losing their cigarette-smoking friends, especially if there was nothing to replace those friends.
Meanwhile, the research on the benefits of positive lifestyle kept mounting up. In one 2008 study published in PLoS (JA Dusek lead author), researchers found that the relaxation response in trained meditators switched off cancer-promoting genes.
Changing our lifestyle actually changes our genes, Dr Ornish pointed out. But who wants to change their lifestyle? What Dr Ornish finally figured out was that will power was a nonstarter for individuals, as was the motivation to live longer. "Who wants to live long if you're depressed?" he asked.
What works, he said, is joy, pleasure, freedom. Up went a slide of two tango-dancers - Dr Ornish and his wife. Doing the tango was part of Dr Ornish's exercise routine.
That's when the lightbulb went off: Yes, we need to lead disciplined lives, but we are doomed to failure unless we incorporate fun into our routines. Here, in this Recovery section, are numerous articles about the virtues of good diet, exercise, yoga, meditation, and so on. We know all this stuff works, but what good is any of it if we give up?
Then it occurred to me: None of my lifestyle routines are based on iron will. They all have enjoyment incorporated into them. For instance, my "exercise" is daily walks, water volleyball, and (off and on) dancing. My "diet" is based on my love of cooking, where anything I throw together is both tastier and healthier than restaurant food. My "stress-management" is all about building contemplative time-outs into my schedule. Even my "meditation" has a fun twist - I play the didgeridoo.
In the words of Dr Ornish: "Doing the tango makes your brain grow ... Some of the things that are most fun are good for you."
Glad I thought of it.
***
My previous three pieces reviewed a randomized, double blind, placebo-controlled clinical trial - representing the gold standard of scientific research - that told us nothing. My humble little reader poll, on the other hand, does not even meet the lowest standards of research. But I ask you: Did it tell you something?
Labels:
Dean Ornish,
fear,
John McManamy,
recovery,
relationships
Wednesday, February 16, 2011
Gold Standard Clinical Trials - Science or Marketing?: Part III
The story so far ...
At the 12th International Congress on Schizophrenia Research in April 2009, J&J debuted a “randomized, double blind, placebo-controlled” study which found its antipsychotic Invega produced a better result on a population of schizoaffective patients than did the placebo.
Researchers point to studies of this type as representing the gold standard of clinical research, but there is a major fallacy in their reasoning, and this study in particular represents a splendid example: Although the methodology of the study was flawless - even dazzling - the result showed us nothing. We already knew antipsychotics, including Invega, worked (with obvious limitations) for conditions involving psychosis. Psychiatrists already prescribe antipsychotics to patients with schizoaffective.
The result was meaningful to one party, and one party only: J&J (which owns Janssen, which manufactures Invega). Thanks to the success of this trial (and to the decidedly less convincing success of an earlier one), J&J had a bullet-proof brief to take to the FDA. In July, the company announced in a press release:
“The U.S. Food and Drug Administration (FDA) today approved the first and only [my emphasis] antipsychotic for the acute treatment of schizoaffective disorder.”
J&J had received clearance to market its Invega as a treatment for schizoaffective - which, since it was the only player in the field, translated to a golden opportunity to market an illness rather than simply a product. Thus, in its press release:
Among people who frequently use mental health services, schizoaffective disorder may account for approximately 24 percent of cases.
And again:
“Schizoaffective disorder can be challenging to diagnose because of the broad range of symptoms patients experience," said Nina Schooler PhD, SUNY Downstate Medical Center.
And again:
"Schizoaffective disorder is a chronic, disabling condition," said Husseini Manji MD, FRCPC, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Pharmaceutical Research & Development. "This new indication for Invega further demonstrates Janssen's commitment to helping people with serious mental illnesses."
In the article of the second study, published in the Oct, 2010 Journal of Clinical Psychiatry, we are told that schizoaffective was first identified in 1933, and the first study article in the April JCP we are informed that:
Although schizoaffective disorder occurs less commonly than schizophrenia, it may account for up to one-quarter of admissions to inpatient mental health facilities.
Back in the glory days of Pharma, J&J would have sponsored at least two dinner (or luncheon or breakfast) symposia at the American Psychiatric Association’s annual meeting. Anywhere from five hundred to a thousand psychiatrists would have crowded into a hotel ballroom to hear a panel of experts expound on “Schizoaffective Disorder, the Forgotten Illness” or “Treatment Modalities for Schizoaffective Disorder” or something similar. The psychiatrists (and other clinicians) would have received CME credits for their attendance.
From 2002 to 2009, I must have attended more than 60 symposia of this nature at APAs. Some of them were blatant advertorials, but most were highly educational and a large number of them were outstanding. I actually recall congratulating some Wyeth people for sponsoring a luncheon symposium the year before that had nothing to do with depression or Effexor. They looked at me funny, as if to say, “How did we screw that up?”
But in the eight consecutive APAs I attended, never once did I see in the program an industry-sponsored symposium devoted to schizoaffective disorder. If I had, I’m sure I would have penciled it in.
The APA has done away with industry-sponsored symposia at its annual meetings, but J&J would have had ample opportunity to get out the word in the exhibit hall. I did not attend last year’s APA, but I guarantee any clinician approaching their exhibit could have watched a multimedia display on schizoaffective, helped themselves to the literature, put their names on a contact list, and had their questions answered by a phalanx of J&J eager beavers. If the clinician expressed an interest in knowing more, one of the eager beavers would have escorted him or her to a back area to talk one-on-one with a J&J big cheese.
Meanwhile, J&J would have been getting out the word in the poster area of the annual meeting. Perhaps attendees there would have viewed the same poster I did at the Schizophrenia Congress. In all likelihood they would have been exposed to many many more, of little significance, something like “Paliperidone ER Taken with Bottled Water vs Tap Water in a Nursing Home Mongolian Population with Schizoaffective Disorder.”
The multiple poster effect would have been wall-to-wall, marketing dressed up as research, with illness and product occupying an attendee’s entire field of vision. Working the posters would be an academic superstar with his or her minions, eager (okay, perhaps not eager) to answer questions.
In the meantime, away from the APA, J&J would be staging its own events with expert speakers, as well as launching its drug reps on special missions of search and sell. Moreover, they would be placing articles in publications. In a recent piece on his Carlat Psychiatry Blog, Daniel Carlat, author of “Unhinged,” had this to say about a feature in Current Psychiatry, which goes out free to psychiatrists:
Another promotional CME Supplement was published in October 2010, and is entitled "Differential Diagnosis and Therapeutic Management of Schizoaffective Disorder." It is supported by Janssen, the maker of Invega, which was recently the first medication FDA approved for - you guessed it - schizoaffective disorder. I haven't read it yet, but this is a de facto advertisement simply by virtue of the choice of topic. Janssen makes the only approved product for schizoaffective disorder, and in order to advertise it, they paid off Current Psychiatry to write a huge article about the disorder. It doesn't need to be "biased;" it just needs to be focused on a topic that is of inherent commercial benefit to the supporter.
The article doesn’t tell us what we don’t already know about about schizoaffective, but it does hit on all the talking points in the J&J press release and related literature, including the fact that:
Only 2 randomized, double-blind, placebo-controlled studies of an atypical antipsychotic (paliperidone extended-release, now FDA-approved for the treatment of SAD), have been conducted in a well-defined SAD patient population.
Even a squeaky-clean expert in a forum uncorrupted by Pharma would be obliged to mention something to this effect. There is no way of avoiding it, and that is the beauty of J&J’s strategy.
But when all it said and done, psychiatrists will not be changing the way they treat patients with psychotic features, whether you call it schizoaffective or something else. They will still use an antipsychotic, just as they have been doing for the last fifty years. It’s just that a few more of them will be doing it with Invega.
At the 12th International Congress on Schizophrenia Research in April 2009, J&J debuted a “randomized, double blind, placebo-controlled” study which found its antipsychotic Invega produced a better result on a population of schizoaffective patients than did the placebo.
Researchers point to studies of this type as representing the gold standard of clinical research, but there is a major fallacy in their reasoning, and this study in particular represents a splendid example: Although the methodology of the study was flawless - even dazzling - the result showed us nothing. We already knew antipsychotics, including Invega, worked (with obvious limitations) for conditions involving psychosis. Psychiatrists already prescribe antipsychotics to patients with schizoaffective.
The result was meaningful to one party, and one party only: J&J (which owns Janssen, which manufactures Invega). Thanks to the success of this trial (and to the decidedly less convincing success of an earlier one), J&J had a bullet-proof brief to take to the FDA. In July, the company announced in a press release:
“The U.S. Food and Drug Administration (FDA) today approved the first and only [my emphasis] antipsychotic for the acute treatment of schizoaffective disorder.”
J&J had received clearance to market its Invega as a treatment for schizoaffective - which, since it was the only player in the field, translated to a golden opportunity to market an illness rather than simply a product. Thus, in its press release:
Among people who frequently use mental health services, schizoaffective disorder may account for approximately 24 percent of cases.
And again:
“Schizoaffective disorder can be challenging to diagnose because of the broad range of symptoms patients experience," said Nina Schooler PhD, SUNY Downstate Medical Center.
And again:
"Schizoaffective disorder is a chronic, disabling condition," said Husseini Manji MD, FRCPC, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Pharmaceutical Research & Development. "This new indication for Invega further demonstrates Janssen's commitment to helping people with serious mental illnesses."
In the article of the second study, published in the Oct, 2010 Journal of Clinical Psychiatry, we are told that schizoaffective was first identified in 1933, and the first study article in the April JCP we are informed that:
Although schizoaffective disorder occurs less commonly than schizophrenia, it may account for up to one-quarter of admissions to inpatient mental health facilities.
Back in the glory days of Pharma, J&J would have sponsored at least two dinner (or luncheon or breakfast) symposia at the American Psychiatric Association’s annual meeting. Anywhere from five hundred to a thousand psychiatrists would have crowded into a hotel ballroom to hear a panel of experts expound on “Schizoaffective Disorder, the Forgotten Illness” or “Treatment Modalities for Schizoaffective Disorder” or something similar. The psychiatrists (and other clinicians) would have received CME credits for their attendance.
From 2002 to 2009, I must have attended more than 60 symposia of this nature at APAs. Some of them were blatant advertorials, but most were highly educational and a large number of them were outstanding. I actually recall congratulating some Wyeth people for sponsoring a luncheon symposium the year before that had nothing to do with depression or Effexor. They looked at me funny, as if to say, “How did we screw that up?”
But in the eight consecutive APAs I attended, never once did I see in the program an industry-sponsored symposium devoted to schizoaffective disorder. If I had, I’m sure I would have penciled it in.
The APA has done away with industry-sponsored symposia at its annual meetings, but J&J would have had ample opportunity to get out the word in the exhibit hall. I did not attend last year’s APA, but I guarantee any clinician approaching their exhibit could have watched a multimedia display on schizoaffective, helped themselves to the literature, put their names on a contact list, and had their questions answered by a phalanx of J&J eager beavers. If the clinician expressed an interest in knowing more, one of the eager beavers would have escorted him or her to a back area to talk one-on-one with a J&J big cheese.
Meanwhile, J&J would have been getting out the word in the poster area of the annual meeting. Perhaps attendees there would have viewed the same poster I did at the Schizophrenia Congress. In all likelihood they would have been exposed to many many more, of little significance, something like “Paliperidone ER Taken with Bottled Water vs Tap Water in a Nursing Home Mongolian Population with Schizoaffective Disorder.”
The multiple poster effect would have been wall-to-wall, marketing dressed up as research, with illness and product occupying an attendee’s entire field of vision. Working the posters would be an academic superstar with his or her minions, eager (okay, perhaps not eager) to answer questions.
In the meantime, away from the APA, J&J would be staging its own events with expert speakers, as well as launching its drug reps on special missions of search and sell. Moreover, they would be placing articles in publications. In a recent piece on his Carlat Psychiatry Blog, Daniel Carlat, author of “Unhinged,” had this to say about a feature in Current Psychiatry, which goes out free to psychiatrists:
Another promotional CME Supplement was published in October 2010, and is entitled "Differential Diagnosis and Therapeutic Management of Schizoaffective Disorder." It is supported by Janssen, the maker of Invega, which was recently the first medication FDA approved for - you guessed it - schizoaffective disorder. I haven't read it yet, but this is a de facto advertisement simply by virtue of the choice of topic. Janssen makes the only approved product for schizoaffective disorder, and in order to advertise it, they paid off Current Psychiatry to write a huge article about the disorder. It doesn't need to be "biased;" it just needs to be focused on a topic that is of inherent commercial benefit to the supporter.
The article doesn’t tell us what we don’t already know about about schizoaffective, but it does hit on all the talking points in the J&J press release and related literature, including the fact that:
Only 2 randomized, double-blind, placebo-controlled studies of an atypical antipsychotic (paliperidone extended-release, now FDA-approved for the treatment of SAD), have been conducted in a well-defined SAD patient population.
Even a squeaky-clean expert in a forum uncorrupted by Pharma would be obliged to mention something to this effect. There is no way of avoiding it, and that is the beauty of J&J’s strategy.
But when all it said and done, psychiatrists will not be changing the way they treat patients with psychotic features, whether you call it schizoaffective or something else. They will still use an antipsychotic, just as they have been doing for the last fifty years. It’s just that a few more of them will be doing it with Invega.
Labels:
clinical trials,
Invega,
John McManamy,
schizoaffective
Monday, February 14, 2011
Gold Standard Clinical Trials - Science or Marketing?: Part II
Moving right along ...
In my previous post, I gave an example of a gold-standard clinical trial that told us next to nothing. The study, which debuted as a poster at the 12th International Congress on Schizophrenia Research in April, 2009, found that J&J’s antipsychotic Invega worked better than a sugar pill in reducing PANSS scores in patients with schizoaffective disorder.
PANSS is a 30-point rating scale used to assess patients for schizophrenia. But there is a twist with patients with schizoaffective, as they also experience mood symptoms. Therefore, the study also measured for depression (using the HAM-D) and mania (using the Young Mania Scale). But clinical trials are only allowed to measure for one thing, so reduction in PANSS scores became the “primary outcome," also known as "primary endpoint.”
The way I heard this explained to me: Suppose a study measured for five different results. Suppose there was only a 20 percent chance of each result coming up positive. That would mean a 100 percent chance of one result coming up positive, which the study sponsor could trumpet as evidence for the success of the treatment. There is value in data from “secondary endpoints,” but you could use secondary endpoint logic to argue that the Steelers beat the Packers in the Super Bowl.
You have to select your primary outcome before the study. No picking the most desirable one when it’s all over.
Okay, now that we’ve agreed on the primary outcome, let’s round up our schizoaffective patients and get crackin’. Um, define schizoaffective. From the DSM-IV:
An uninterrupted period of illness during which, at some time, there is either a Major Depressive Episode, a Manic Episode, or a Mixed Episode concurrent with symptoms that meet Criterion A for Schizophrenia.
Clear as day, right? The DSM-5 work group responsible for coming up with something better actually said, “the current DSM-IV-TR diagnosis schizoaffective disorder is unreliable,” then did not come up with something better.
Common sense dictates that an unreliable diagnosis automatically calls into question the credibility of any study of this sort from the very outset, gold standard or not. I would extend this line of reasoning to include all antidepressant trials on "depressed" patients (what the hell is depression, anyway?), as well, but that's me mounting my hobby horse.
But the practical problem remains. Patients with schizoaffective are not going to exactly materialize for a clinical trial, especially if they’re being diagnosed with something else. To compensate, J&J took the highly unusual step of recruiting patients from more than 40 centers worldwide, including India, Russia, the Ukraine, and all across the US. This way, they were able to round up a total of 311 patients who met DSM-IV criteria.
Keep in mind, in any meds trial both the drug group and placebo group need to be as close to an exact match as possible. The “randomization” in “randomized double-blind placebo-controlled” trials means patients are assigned to different groups by chance rather than choice (thereby preventing abuses such as clinicians selecting good prognosis patients for the drug group). It’s not as simple as a coin toss, especially across more than 40 different centers worldwide. Give J&J credit where credit is due.
There was an additional complication to this trial: The patients were also on mood stabilizers and/or antidepressants. Still, antipsychotics have a very good trial track record in the PANSS challenge. Even accounting for all the special challenges of this particular trial, how hard can a glorified counting exercise be, right? Did someone say “discontinuation”?
It turned out about 40 percent of the patients dropped out of the study, about equal between the Invega and placebo groups. What this tells me is that when a doctor prescribes this med for this illness there is a four in ten percent chance of failure, even before the patient walks out the door. But this has never bothered the people putting together these “gold standard” studies.
To compensate, the J&J people employed a standard statistical fiction known as “intent-to-treat analysis,” which includes the drop-outs in the final tally, as if these patients had completed the study. One way of implementing this is with “last observation carried forward” (LOCF). Thus, if a patient drops at at week two of a six-week trial, his or her two-week result is “carried forward” to the final week.
There is a legitimate reason for doing this. Patients who drop out of drug trials are more likely to be bad responders. Thus, if only good responders stay in the study, the results are likely to overstate the benefits of the test drug.
To me, however, a high drop-out rate means that any positive finding is next to useless. But who listens to me? Anyway, now that we’ve jumped through all the various statistical hoops, we’re finally ready to get down to some serious counting. Oops! - did someone say placebo?
Placebos are the bane of all clinical trials, especially for psychiatric meds. In an earlier trial conducted by J&J, the placebo group fared almost as well as the Invega group. The second time out, those on the Invega did no better than before, but those on the placebo did a lot worse (perhaps due to a bad batch of placebos). Thus, the J&J investigators had “clear separation” from the placebo group.
Thus, instead of tearing their hair out, J&J had reason to celebrate. All their hard work had paid off. Between the two trials, they now had an airtight case to take to the FDA. Indeed, six months after the trial results came through in February, three months after J&J debuted its study as a poster in April, in July the company proudly announced in a press release:
“The U.S. Food and Drug Administration (FDA) today approved the first and only [my emphasis] antipsychotic for the acute treatment of schizoaffective disorder.”
Mission accomplished: J&J had received clearance to market its Invega as a treatment for schizoaffective.
To market, to market ... That was the real - and only relevant - endpoint to this gold-standard study.
More to come ....
In my previous post, I gave an example of a gold-standard clinical trial that told us next to nothing. The study, which debuted as a poster at the 12th International Congress on Schizophrenia Research in April, 2009, found that J&J’s antipsychotic Invega worked better than a sugar pill in reducing PANSS scores in patients with schizoaffective disorder.
PANSS is a 30-point rating scale used to assess patients for schizophrenia. But there is a twist with patients with schizoaffective, as they also experience mood symptoms. Therefore, the study also measured for depression (using the HAM-D) and mania (using the Young Mania Scale). But clinical trials are only allowed to measure for one thing, so reduction in PANSS scores became the “primary outcome," also known as "primary endpoint.”
The way I heard this explained to me: Suppose a study measured for five different results. Suppose there was only a 20 percent chance of each result coming up positive. That would mean a 100 percent chance of one result coming up positive, which the study sponsor could trumpet as evidence for the success of the treatment. There is value in data from “secondary endpoints,” but you could use secondary endpoint logic to argue that the Steelers beat the Packers in the Super Bowl.
You have to select your primary outcome before the study. No picking the most desirable one when it’s all over.
Okay, now that we’ve agreed on the primary outcome, let’s round up our schizoaffective patients and get crackin’. Um, define schizoaffective. From the DSM-IV:
An uninterrupted period of illness during which, at some time, there is either a Major Depressive Episode, a Manic Episode, or a Mixed Episode concurrent with symptoms that meet Criterion A for Schizophrenia.
Clear as day, right? The DSM-5 work group responsible for coming up with something better actually said, “the current DSM-IV-TR diagnosis schizoaffective disorder is unreliable,” then did not come up with something better.
Common sense dictates that an unreliable diagnosis automatically calls into question the credibility of any study of this sort from the very outset, gold standard or not. I would extend this line of reasoning to include all antidepressant trials on "depressed" patients (what the hell is depression, anyway?), as well, but that's me mounting my hobby horse.
But the practical problem remains. Patients with schizoaffective are not going to exactly materialize for a clinical trial, especially if they’re being diagnosed with something else. To compensate, J&J took the highly unusual step of recruiting patients from more than 40 centers worldwide, including India, Russia, the Ukraine, and all across the US. This way, they were able to round up a total of 311 patients who met DSM-IV criteria.
Keep in mind, in any meds trial both the drug group and placebo group need to be as close to an exact match as possible. The “randomization” in “randomized double-blind placebo-controlled” trials means patients are assigned to different groups by chance rather than choice (thereby preventing abuses such as clinicians selecting good prognosis patients for the drug group). It’s not as simple as a coin toss, especially across more than 40 different centers worldwide. Give J&J credit where credit is due.
There was an additional complication to this trial: The patients were also on mood stabilizers and/or antidepressants. Still, antipsychotics have a very good trial track record in the PANSS challenge. Even accounting for all the special challenges of this particular trial, how hard can a glorified counting exercise be, right? Did someone say “discontinuation”?
It turned out about 40 percent of the patients dropped out of the study, about equal between the Invega and placebo groups. What this tells me is that when a doctor prescribes this med for this illness there is a four in ten percent chance of failure, even before the patient walks out the door. But this has never bothered the people putting together these “gold standard” studies.
To compensate, the J&J people employed a standard statistical fiction known as “intent-to-treat analysis,” which includes the drop-outs in the final tally, as if these patients had completed the study. One way of implementing this is with “last observation carried forward” (LOCF). Thus, if a patient drops at at week two of a six-week trial, his or her two-week result is “carried forward” to the final week.
There is a legitimate reason for doing this. Patients who drop out of drug trials are more likely to be bad responders. Thus, if only good responders stay in the study, the results are likely to overstate the benefits of the test drug.
To me, however, a high drop-out rate means that any positive finding is next to useless. But who listens to me? Anyway, now that we’ve jumped through all the various statistical hoops, we’re finally ready to get down to some serious counting. Oops! - did someone say placebo?
Placebos are the bane of all clinical trials, especially for psychiatric meds. In an earlier trial conducted by J&J, the placebo group fared almost as well as the Invega group. The second time out, those on the Invega did no better than before, but those on the placebo did a lot worse (perhaps due to a bad batch of placebos). Thus, the J&J investigators had “clear separation” from the placebo group.
Thus, instead of tearing their hair out, J&J had reason to celebrate. All their hard work had paid off. Between the two trials, they now had an airtight case to take to the FDA. Indeed, six months after the trial results came through in February, three months after J&J debuted its study as a poster in April, in July the company proudly announced in a press release:
“The U.S. Food and Drug Administration (FDA) today approved the first and only [my emphasis] antipsychotic for the acute treatment of schizoaffective disorder.”
Mission accomplished: J&J had received clearance to market its Invega as a treatment for schizoaffective.
To market, to market ... That was the real - and only relevant - endpoint to this gold-standard study.
More to come ....
Labels:
clinical trials,
Invega,
John McManamy,
paliperidone
Sunday, February 13, 2011
Gold Standard Clinical Trials - Science or Marketing?
This is the second in a new series on analyzing information. Credit Robert Whitaker’s “Anatomy of an Epidemic” for getting the ball rolling, as there is no way of critiquing his book without evaluating the evidence he relied upon. Only then can we ask ourselves if his conclusions are justifiable.
This is a different proposition entirely than whether Whitaker is right or wrong. You can decide that for yourself.
In my previous piece, I commented on some findings at the very bottom of the evidence food chain (a series of wholly unscientific reader polls I had conducted here), but that actually told us something. In this piece, I will flip it. I will talk about a study at the very top of the food chain, but that tells us nothing. Let’s get started ...
Two years ago, in my capacity as a journalist, I was at the 12th International Congress on Schizophrenia Research in San Diego, just down the hill from where I live. The top brain scientists in the world were presenting and in attendance, including 2000 Nobel Laureate Arvid Carlsson. I recall going to a table with my morning coffee and greeting the researchers there with, “Hi, I’m the only C student at this table.”
Part of the Congress involved poster sessions, where scientists stand in front of blow-ups of their latest findings. This affords an invaluable opportunity for the researchers at the conference to engage their fellow researchers in one-on-one discussion. It also affords a golden opportunity for people like me to walk up to some future Nobel Laureate and ask, “What’s a neuron?”
The first three or four days of posters involved cutting edge brain research. I was like a kid in a candy store ... a wrestler in a chair factory, a hippie in a drum circle. (Did you see that Super Bowl commercial?) The last day of the conference featured posters on treatment. Instantly, I felt I had been sucked back in time a half century.
Some very enthusiastic Johnson&Johnson people informed me of a new study of theirs that shed some very important new light on schizoaffective disorder.
Really? I thought. Schizoaffective is probably the most confusing diagnostic classification in the entire DSM. Everyone agrees that it has something to do with that undelineated middle ground where bipolar and schizophrenia bleed into one another, but what is it exactly? Schizophrenia lite? Bipolar heavy? Some kind of schizophrenia-bipolar mix? Or a stand-alone illness in its own right?
Naturally, I was interested. I looked at the poster. "A Randomized, Double Blind, Placebo-Controlled Study of Flexible Dose Paliperidone ER in the Treatment of Patients with Schizoaffective Disorder," I read.
I smiled politely, engaged in very short chit-chat, then made my way to other posters. In one glance, I knew, the study told me nothing. Here’s the deal:
Randomized, double blind, placebo-controlled studies are the gold standard of treatment research. Perhaps the most celebrated example of a clinical trial is James Lind’s 1747 experiment involving 12 scurvy-infected sailors. He divided his patients into six pairs. Five of the pairs showed no improvement. Of the pair receiving oranges and lemons, one had fully recovered after five days, the other had almost recovered. (Then they ran out of fruit.)
A more refined study would have pitted a much larger group of orange-and-lemon people against a proportionally large group taking a look-alike, taste-alike placebo (say a citrus pill vs a sugar pill). To keep the study honest, one would have made sure the clinicians handing out the pills had no way of knowing which pill was which (the double-blind).
I knew at a glance the J&J people had all their “i”s dotted and “t”s crossed. Studies of this nature are immensely expensive - my best guess is the $20 million-range - designed by some of the smartest people in the world overseeing an immense and highly complex undertaking where an infinity of things can go wrong (and often do).
The catch? Even though the study was conducted scientifically, to rigorous standards, it was not a scientific study. It was a marketing exercise.
Paliperidone is the generic name for J&J’s recently-approved Invega, which is Son of Risperdal. Risperdal represents the first of the new-generation atypical antipsychotics (discounting Clozaril) introduced in the early 1990s and hyped as superior to old-generation antipsychotics.
We already know that as problematic as antipsychotics may be, they are very effective in knocking out psychosis. The first studies involving Thorazine proved that six decades ago. Since then, antipsychotics have been the treatment of choice for schizophrenia and any condition involving psychosis, including bipolar and schizoaffective, accounting for some $20 billion annually in sales.
So what’s new? Nothing much, really, except that no drug company had ever undertaken a trial on a schizoaffective population. What was the point?
Keep in mind that when James Lind was investigating scurvy, the British Royal Navy was not issuing citrus fruit to its sailors. His findings would give them cause to change their practice, though it would take them another fifty years to get around to it.
Contrast this with the Invega study. Is a clinician, reading this study, really going to change his or her practice by putting all his schizoaffective patients on an antipsychotic? He already has them on an antipsychotic.
But could the study possibly be persuasive in getting a clinician to change her practice from prescribing say Geodon or Zyprexa to Invega? Ah, a marketing question.
More to come ...
This is a different proposition entirely than whether Whitaker is right or wrong. You can decide that for yourself.
In my previous piece, I commented on some findings at the very bottom of the evidence food chain (a series of wholly unscientific reader polls I had conducted here), but that actually told us something. In this piece, I will flip it. I will talk about a study at the very top of the food chain, but that tells us nothing. Let’s get started ...
Two years ago, in my capacity as a journalist, I was at the 12th International Congress on Schizophrenia Research in San Diego, just down the hill from where I live. The top brain scientists in the world were presenting and in attendance, including 2000 Nobel Laureate Arvid Carlsson. I recall going to a table with my morning coffee and greeting the researchers there with, “Hi, I’m the only C student at this table.”
Part of the Congress involved poster sessions, where scientists stand in front of blow-ups of their latest findings. This affords an invaluable opportunity for the researchers at the conference to engage their fellow researchers in one-on-one discussion. It also affords a golden opportunity for people like me to walk up to some future Nobel Laureate and ask, “What’s a neuron?”
The first three or four days of posters involved cutting edge brain research. I was like a kid in a candy store ... a wrestler in a chair factory, a hippie in a drum circle. (Did you see that Super Bowl commercial?) The last day of the conference featured posters on treatment. Instantly, I felt I had been sucked back in time a half century.
Some very enthusiastic Johnson&Johnson people informed me of a new study of theirs that shed some very important new light on schizoaffective disorder.
Really? I thought. Schizoaffective is probably the most confusing diagnostic classification in the entire DSM. Everyone agrees that it has something to do with that undelineated middle ground where bipolar and schizophrenia bleed into one another, but what is it exactly? Schizophrenia lite? Bipolar heavy? Some kind of schizophrenia-bipolar mix? Or a stand-alone illness in its own right?
Naturally, I was interested. I looked at the poster. "A Randomized, Double Blind, Placebo-Controlled Study of Flexible Dose Paliperidone ER in the Treatment of Patients with Schizoaffective Disorder," I read.
I smiled politely, engaged in very short chit-chat, then made my way to other posters. In one glance, I knew, the study told me nothing. Here’s the deal:
Randomized, double blind, placebo-controlled studies are the gold standard of treatment research. Perhaps the most celebrated example of a clinical trial is James Lind’s 1747 experiment involving 12 scurvy-infected sailors. He divided his patients into six pairs. Five of the pairs showed no improvement. Of the pair receiving oranges and lemons, one had fully recovered after five days, the other had almost recovered. (Then they ran out of fruit.)
A more refined study would have pitted a much larger group of orange-and-lemon people against a proportionally large group taking a look-alike, taste-alike placebo (say a citrus pill vs a sugar pill). To keep the study honest, one would have made sure the clinicians handing out the pills had no way of knowing which pill was which (the double-blind).
I knew at a glance the J&J people had all their “i”s dotted and “t”s crossed. Studies of this nature are immensely expensive - my best guess is the $20 million-range - designed by some of the smartest people in the world overseeing an immense and highly complex undertaking where an infinity of things can go wrong (and often do).
The catch? Even though the study was conducted scientifically, to rigorous standards, it was not a scientific study. It was a marketing exercise.
Paliperidone is the generic name for J&J’s recently-approved Invega, which is Son of Risperdal. Risperdal represents the first of the new-generation atypical antipsychotics (discounting Clozaril) introduced in the early 1990s and hyped as superior to old-generation antipsychotics.
We already know that as problematic as antipsychotics may be, they are very effective in knocking out psychosis. The first studies involving Thorazine proved that six decades ago. Since then, antipsychotics have been the treatment of choice for schizophrenia and any condition involving psychosis, including bipolar and schizoaffective, accounting for some $20 billion annually in sales.
So what’s new? Nothing much, really, except that no drug company had ever undertaken a trial on a schizoaffective population. What was the point?
Keep in mind that when James Lind was investigating scurvy, the British Royal Navy was not issuing citrus fruit to its sailors. His findings would give them cause to change their practice, though it would take them another fifty years to get around to it.
Contrast this with the Invega study. Is a clinician, reading this study, really going to change his or her practice by putting all his schizoaffective patients on an antipsychotic? He already has them on an antipsychotic.
But could the study possibly be persuasive in getting a clinician to change her practice from prescribing say Geodon or Zyprexa to Invega? Ah, a marketing question.
More to come ...
Labels:
clinical trials,
Invega,
John McManamy,
paliperidone,
schizoaffective
Friday, February 11, 2011
The Whitaker Aftermath - Assessing the Quality of Information
Over the last several days, I have been commenting on the commenters to Robert Whitaker’s commentary, “Anatomy of an Epidemic.” Much of the discussion - actually all of it - focuses on the quality of the studies Whitaker relied on to support his controversial thesis that psychiatric disabilities are on the rise because of the widespread use of psychiatric meds, not despite them.
As a general rule, the more startling an assertion, the higher the level of proof we demand. Thus, if I say, “I have my driver’s license,” you are not likely to ask me to pull it out of my wallet and show it to you. (Ironically, three years ago I did not have a driver’s license, so the joke would have been on you.) You get the picture.
Accordingly, any spirited debate you run across concerning the studies Whitaker relies on are not mere academic quibbles. If his sources are faulty, or if he is making conclusions unsupported by the data, then we can easily dismiss Whitaker.
I’ve been reporting on mental health studies since 1999. My approach to looking at information as a journalist is quite a bit different from that of an academic researcher or a clinician looking at the same information. In many ways, my criteria for reporting is far more strict. And in other key ways, far more loose.
Basically, my standard is that we work from the best set of facts we have for the purpose of improving our understanding right now, and I suspect this is where Whitaker is coming from. We don’t sit around waiting for the ultimate gold standard study that is never likely to materialize. An example:
In 2009, I ran a series of reader polls on Knowledge is Necessity that found: 1) Four in five rated their meds as either the single most important tool in managing their wellness or as just as important as their other wellness tools; 2) Only 14 percent reported their meds worked “very well”; 3) Only 14 percent reported they were back to where they wanted to be.
Something clearly is very wrong with this picture. My series of polls indicate we dangerously over-rely on our meds and one result is we don’t get well. (You can read all about it on mcmanweb.)
But this is a reader poll, not a scientific study. A scientific study of this sort would probably cost in the neighborhood of several hundred thousand to get done. Maybe more. I would probably have to spend two years hustling for the same grant money six zillion other researchers are competing for, a year or more working with a team of experts designing and implementing the study and processing the data, and another year or two actually getting the thing published, assuming I was lucky enough to find an editor interested in reading it.
In all likelihood, my submission would be reviewed by an academic “referee” in the pocket of the drug industry who would find a million reasons to reject it.
But assuming my submission were accepted, there would be six to 12 months of revisions before my research saw the light of day. Nine-tenths of the study article would involve me explaining my methodology. The other one-tenth would be divided between the facts we need to know and my interpretation of what the facts mean. A journal editor would have me on a very short leash. My really interesting observations would likely be edited out, to the point that the study yielded little of value to anyone.
So - five or six or more years, several hundred thousand dollars, a team of experts, and endless aggravation for a by-now nearly meaningless study that maybe 30 people would read. If I were lucky, Robert Whitaker would find out about my study, mention it in his next book, make me famous, and draw all the conclusions that I was not allowed to make.
Then enraged academics like Andrew Nierenberg would attack him for relying on a low-quality study that really said nothing of the sort and moreover came from a nobody like me.
See what we’re up against?
***
This is the first in a series of pieces that examines the quality of mental health information, from different types of academic studies to clinical trials to media reports and blogs to informal surveys to personal experience. We will look at the tricks of the trade employed by the drug industry, academic researchers, journalists, and bloggers. We will look at why a so-called gold-standard scientific study may not be worth the paper it is printed on and why an unscientific reader poll may yield quality information.
Stay tuned ...
As a general rule, the more startling an assertion, the higher the level of proof we demand. Thus, if I say, “I have my driver’s license,” you are not likely to ask me to pull it out of my wallet and show it to you. (Ironically, three years ago I did not have a driver’s license, so the joke would have been on you.) You get the picture.
Accordingly, any spirited debate you run across concerning the studies Whitaker relies on are not mere academic quibbles. If his sources are faulty, or if he is making conclusions unsupported by the data, then we can easily dismiss Whitaker.
I’ve been reporting on mental health studies since 1999. My approach to looking at information as a journalist is quite a bit different from that of an academic researcher or a clinician looking at the same information. In many ways, my criteria for reporting is far more strict. And in other key ways, far more loose.
Basically, my standard is that we work from the best set of facts we have for the purpose of improving our understanding right now, and I suspect this is where Whitaker is coming from. We don’t sit around waiting for the ultimate gold standard study that is never likely to materialize. An example:
In 2009, I ran a series of reader polls on Knowledge is Necessity that found: 1) Four in five rated their meds as either the single most important tool in managing their wellness or as just as important as their other wellness tools; 2) Only 14 percent reported their meds worked “very well”; 3) Only 14 percent reported they were back to where they wanted to be.
Something clearly is very wrong with this picture. My series of polls indicate we dangerously over-rely on our meds and one result is we don’t get well. (You can read all about it on mcmanweb.)
But this is a reader poll, not a scientific study. A scientific study of this sort would probably cost in the neighborhood of several hundred thousand to get done. Maybe more. I would probably have to spend two years hustling for the same grant money six zillion other researchers are competing for, a year or more working with a team of experts designing and implementing the study and processing the data, and another year or two actually getting the thing published, assuming I was lucky enough to find an editor interested in reading it.
In all likelihood, my submission would be reviewed by an academic “referee” in the pocket of the drug industry who would find a million reasons to reject it.
But assuming my submission were accepted, there would be six to 12 months of revisions before my research saw the light of day. Nine-tenths of the study article would involve me explaining my methodology. The other one-tenth would be divided between the facts we need to know and my interpretation of what the facts mean. A journal editor would have me on a very short leash. My really interesting observations would likely be edited out, to the point that the study yielded little of value to anyone.
So - five or six or more years, several hundred thousand dollars, a team of experts, and endless aggravation for a by-now nearly meaningless study that maybe 30 people would read. If I were lucky, Robert Whitaker would find out about my study, mention it in his next book, make me famous, and draw all the conclusions that I was not allowed to make.
Then enraged academics like Andrew Nierenberg would attack him for relying on a low-quality study that really said nothing of the sort and moreover came from a nobody like me.
See what we’re up against?
***
This is the first in a series of pieces that examines the quality of mental health information, from different types of academic studies to clinical trials to media reports and blogs to informal surveys to personal experience. We will look at the tricks of the trade employed by the drug industry, academic researchers, journalists, and bloggers. We will look at why a so-called gold-standard scientific study may not be worth the paper it is printed on and why an unscientific reader poll may yield quality information.
Stay tuned ...
Labels:
information,
John McManamy,
Robert Whitaker,
studies
Carlat's Response to Whitaker - When is Speculation Justified?
We left off with a psychiatrist, via his blog, actually engaging Robert Whitaker, author of “Anatomy of an Epidemic,” in a discussion. In the first of two blog posts, Daniel Carlat, producer of The Carlat Report and author of “Unhinged,” acknowledged that Whitaker had “his basic facts right,” but disagreed “with his interpretation of the facts.”
This was a refreshing contrast to Andrew Nierenberg’s Psychiatrists Gone Wild performance in reaction to Whitaker’s recent grand rounds at Mass General.
Whitaker’s central thesis is that the reason psychiatric disabilities are much higher today is because of widespread meds use rather than despite widespread meds use. Dr Carlat says there are more plausible explanations for the higher disabilities rate, namely people today are more likely to pick up both a diagnosis and a disability simply by passing Go.
This lack of constancy, contends Dr Carlat in his second post, applies to the diagnosis of schizophrenia, as well, which back in the old days seemed to have been used as a catch-all for all manner of unusual behavior. The pre-DSM-III (1980) studies Whitaker largely relies on, says Dr Carlat, would have included a lot of patients who did not have true schizophrenia and thus would have done just fine without a schizophrenia med.
Dr Carlat has a point, but if you were to exclude the studies Whitaker cites based solely on this criteria, then you need to exclude EVERY schizophrenia study from this era, including authoritative gene studies that showed schizophrenia is clustered in families and is inherited from generation to generation, as well as all the evidence in support of Thorazine’s efficacy.
But for the sake of argument, let’s throw out two ancient long-term WHO studies that Whitaker heavily relied on showing that schizophrenia patients in developing countries (where psychiatric meds are in short supply) had a far better course and outcome than patients in developed countries. Let’s substitute, instead, a 2004 WHO study that employed DSM-IV criteria to measure 12-month prevalence rates of various serious mental disorders (not including schizophrenia) in 14 countries. That survey found, amongst other things, that Nigeria had the lowest rate of mood disorders (0.8 percent) while the US had the highest (9.6 percent).
Not exactly on point, but definitely on pattern. Something strange is clearly going on.
There is one modern study almost entirely on point, which Whitaker employs as his trump card. This is the now famous 2007 “Harrow study” conducted by Martin Harrow of the University of Illinois, which indicated that schizophrenia patients not on meds fared way better over 15 years than those on meds. The catch is the study measured for something quite a bit different, which Whitaker fails to mention in his book.
Dr Carlat stated the obvious, namely that “observational” studies of this type are not likely to yield definitive conclusions. Moreover, it stands to reason that the ones who do well off their meds are likely to be a different breed of patient.
Indeed, it was precisely this issue that Dr Harrow concerned himself with. The true finding in his study was that a certain subgroup of “good prognosis” patients (such as ones with a prior work history) fared better over the long haul off meds than on meds, suggesting that "not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives."
In an earlier piece, I issued Whitaker a moving violation for reporting this study as if it were a clinical trial testing for the efficacy of antipsychotic medications.
But then comes a point where criticism becomes quibbling. Dr Nierenberg egregiously crossed that line when he went postal on Whitaker. Dr Carlat is in the safe zone, but did he miss the big picture? Basically, if someone is shouting Fire! through a cell phone, you investigate whether there is a fire. You don’t get into a discussion about whether the caller ran over his alloted cell phone minutes.
Pulling data from an earlier study to reach a different type of finding goes on all the time in academia. It’s called a “secondary analysis” and when it’s done right it vastly increases the value of the original data. Basically, Whitaker performed his own secondary analysis.
So then the question becomes one of whether Harrrow’s data justifies Whitaker’s conclusions. The answer is yes - to a point. Clearly the patients who fared best in Harrow’s study were the ones off their meds. Whitaker is on very safe ground here. But then he presses his luck by concluding that it was the antipsychotic medications that worsened the outcomes of the ones on their meds. Here, he has stepped into the quicksand of speculation, and Dr Carlat correctly takes him to task.
In his blog, Whitaker defends himself against earlier similar charges by arguing that the Harrow data applies across all the subgroups of patients in his study. But in a 64-patient study parsed into numerous subgroups, we're taking of differences measured in low single figures. (Thanks to Ruminations on Madness for this observation).
So do we dismiss Whitaker’s speculations as out-of-hand? Absolutely not. The DSM-IV - psychiatry’s diagnostic bible - is basically speculation bound between two covers. Every prescription for a psychiatric med that a doctor writes is a speculation approved by the FDA.
We must never forget the big picture: If our meds worked the way Pharma claims and psychiatry believes, we wouldn’t have mental illness to kick around anymore. Instead, we have an epidemic. So what the hell is going on? Someone has to start speculating. Dr Carlat, to his credit, seems to have acknowledged this in the conclusion to his second post:
Over the last few days, I've spent many hours thinking and writing about Anatomy of an Epidemic. Mostly, I've chipped away at its central thesis, and yet the fact that this powerful book has riveted my attention for so long means something. It's fascinating. It's enthralling. And it is the work of a highly intelligent and inquiring mind - a person who is struggling to understand the nature of psychiatric treatment. Put it on your reading list, and join the debate.
This was a refreshing contrast to Andrew Nierenberg’s Psychiatrists Gone Wild performance in reaction to Whitaker’s recent grand rounds at Mass General.
Whitaker’s central thesis is that the reason psychiatric disabilities are much higher today is because of widespread meds use rather than despite widespread meds use. Dr Carlat says there are more plausible explanations for the higher disabilities rate, namely people today are more likely to pick up both a diagnosis and a disability simply by passing Go.
This lack of constancy, contends Dr Carlat in his second post, applies to the diagnosis of schizophrenia, as well, which back in the old days seemed to have been used as a catch-all for all manner of unusual behavior. The pre-DSM-III (1980) studies Whitaker largely relies on, says Dr Carlat, would have included a lot of patients who did not have true schizophrenia and thus would have done just fine without a schizophrenia med.
Dr Carlat has a point, but if you were to exclude the studies Whitaker cites based solely on this criteria, then you need to exclude EVERY schizophrenia study from this era, including authoritative gene studies that showed schizophrenia is clustered in families and is inherited from generation to generation, as well as all the evidence in support of Thorazine’s efficacy.
But for the sake of argument, let’s throw out two ancient long-term WHO studies that Whitaker heavily relied on showing that schizophrenia patients in developing countries (where psychiatric meds are in short supply) had a far better course and outcome than patients in developed countries. Let’s substitute, instead, a 2004 WHO study that employed DSM-IV criteria to measure 12-month prevalence rates of various serious mental disorders (not including schizophrenia) in 14 countries. That survey found, amongst other things, that Nigeria had the lowest rate of mood disorders (0.8 percent) while the US had the highest (9.6 percent).
Not exactly on point, but definitely on pattern. Something strange is clearly going on.
There is one modern study almost entirely on point, which Whitaker employs as his trump card. This is the now famous 2007 “Harrow study” conducted by Martin Harrow of the University of Illinois, which indicated that schizophrenia patients not on meds fared way better over 15 years than those on meds. The catch is the study measured for something quite a bit different, which Whitaker fails to mention in his book.
Dr Carlat stated the obvious, namely that “observational” studies of this type are not likely to yield definitive conclusions. Moreover, it stands to reason that the ones who do well off their meds are likely to be a different breed of patient.
Indeed, it was precisely this issue that Dr Harrow concerned himself with. The true finding in his study was that a certain subgroup of “good prognosis” patients (such as ones with a prior work history) fared better over the long haul off meds than on meds, suggesting that "not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives."
In an earlier piece, I issued Whitaker a moving violation for reporting this study as if it were a clinical trial testing for the efficacy of antipsychotic medications.
But then comes a point where criticism becomes quibbling. Dr Nierenberg egregiously crossed that line when he went postal on Whitaker. Dr Carlat is in the safe zone, but did he miss the big picture? Basically, if someone is shouting Fire! through a cell phone, you investigate whether there is a fire. You don’t get into a discussion about whether the caller ran over his alloted cell phone minutes.
Pulling data from an earlier study to reach a different type of finding goes on all the time in academia. It’s called a “secondary analysis” and when it’s done right it vastly increases the value of the original data. Basically, Whitaker performed his own secondary analysis.
So then the question becomes one of whether Harrrow’s data justifies Whitaker’s conclusions. The answer is yes - to a point. Clearly the patients who fared best in Harrow’s study were the ones off their meds. Whitaker is on very safe ground here. But then he presses his luck by concluding that it was the antipsychotic medications that worsened the outcomes of the ones on their meds. Here, he has stepped into the quicksand of speculation, and Dr Carlat correctly takes him to task.
In his blog, Whitaker defends himself against earlier similar charges by arguing that the Harrow data applies across all the subgroups of patients in his study. But in a 64-patient study parsed into numerous subgroups, we're taking of differences measured in low single figures. (Thanks to Ruminations on Madness for this observation).
So do we dismiss Whitaker’s speculations as out-of-hand? Absolutely not. The DSM-IV - psychiatry’s diagnostic bible - is basically speculation bound between two covers. Every prescription for a psychiatric med that a doctor writes is a speculation approved by the FDA.
We must never forget the big picture: If our meds worked the way Pharma claims and psychiatry believes, we wouldn’t have mental illness to kick around anymore. Instead, we have an epidemic. So what the hell is going on? Someone has to start speculating. Dr Carlat, to his credit, seems to have acknowledged this in the conclusion to his second post:
Over the last few days, I've spent many hours thinking and writing about Anatomy of an Epidemic. Mostly, I've chipped away at its central thesis, and yet the fact that this powerful book has riveted my attention for so long means something. It's fascinating. It's enthralling. And it is the work of a highly intelligent and inquiring mind - a person who is struggling to understand the nature of psychiatric treatment. Put it on your reading list, and join the debate.
Wednesday, February 9, 2011
Carlat's Response to Whitaker - A Discussion at Last
We left off with a self-proclaimed “refutation” and “repudiation” by Andrew Nierenberg of Harvard that neither refuted nor repudiated “Anatomy of an Epidemic” by Robert Whitaker. In a response to a grand rounds delivered by Whitaker at Mass Gen on Jan 13, Dr Nierenberg accused Whitaker of “misinformation, simplistic interpretations of statistics, faulty reasoning, and wrong conclusions,” but when the dust cleared the perpetrator of these crimes turned out to be Dr Nierenberg himself.
Throw in his gratuitous personal attacks on Whitaker and we have clear evidence of a psychiatrist gone wild. Of all things, Whitaker came out totally unscathed.
I’m sure we can fashion an ancient Chinese proverb from Dr Nierenberg’s oppositionally defiant behavior, but the clear lesson is that virtually all refutations are doomed to fail (even against such palpably absurd beliefs as “creation science”). Refuting the refuter, needless to say, is like shooting fish in a barrel.
So would a more reasoned approach, say one that actually acknowledged the validity of Whitaker’s arguments, have been far more effective? Funny you should ask.
Daniel Carlat produces The Carlat Report and is the author of “Unhinged,” which is highly critical of Pharma marketing dressed up as science. In late Jan, in the first of a two-part review on his blog, Carlat noted:
My overall take is that Whitaker has his basic facts right, and that he communicates them in a compelling style that I envy. But I disagree with his interpretation of the facts.
Now we’re getting somewhere.
Dr Carlat restates Whitaker’s thesis that the steep rise in psychiatric disabilities over recent years has coincided with a similar rise in psychiatric meds prescriptions. Yes, this is true, Dr Carlat agrees, but “correlation does not imply causation.” To say that med use has actually caused the disability, as Whitaker claims, is a stretch. There are other factors involved, Dr Carlat says, including:
There are more psychiatric disorders to diagnose - 297 in the current DSM, about the same as the DSM-III-R from 1987 (at 292), a bit more than the DSM-III of 1980 (at 265), a lot more than the DSM-II of 1968 (at 182), and a whole lot more than the DSM-I of 1952 (at 106). Dr Carlat contends that “the rise in diagnosis has been largely driven by changes in disease classification and subsequent training - not by toxic medications.”
Dr Carlat also notes that because there are more treatments available, doctors have more of an incentive to make a diagnosis. In other words, doctors are not inclined to make a diagnosis for something they cannot treat.
Then Dr Carlat mentions the obvious: That a major reason for the rise in psychiatric disabilities probably has to do with the changed status of psychiatric disabilities. Eligibility has been expanded, thresholds lowered.
To expand on Dr Carlat, a whole disability industry has grown up to facilitate a normally arduous application process. Clinicians and social workers routinely advise even good prognosis patients that they may qualify for disability. A fairly new specialty of disability lawyers is there to assist. Both political parties are more than happy to play along, as those on disability are not counted as being unemployed.
To tie this into a bow: Dr Carlat offers his views by way of “interpretation” rather than “repudiation.” Whitaker may not have shown cause and effect, but neither did he. Instead, Dr Carlat is presenting credible alternatives, supported by his own set of facts. This is the way to make a case.
Let’s forget for the time being whose arguments are more credible. One thing we can all agree on is at last we have a discussion going, something Whitaker wanted all along. Finally, a discussion, not a Nierenberg hissy fit.
More to come ...
Throw in his gratuitous personal attacks on Whitaker and we have clear evidence of a psychiatrist gone wild. Of all things, Whitaker came out totally unscathed.
I’m sure we can fashion an ancient Chinese proverb from Dr Nierenberg’s oppositionally defiant behavior, but the clear lesson is that virtually all refutations are doomed to fail (even against such palpably absurd beliefs as “creation science”). Refuting the refuter, needless to say, is like shooting fish in a barrel.
So would a more reasoned approach, say one that actually acknowledged the validity of Whitaker’s arguments, have been far more effective? Funny you should ask.
Daniel Carlat produces The Carlat Report and is the author of “Unhinged,” which is highly critical of Pharma marketing dressed up as science. In late Jan, in the first of a two-part review on his blog, Carlat noted:
My overall take is that Whitaker has his basic facts right, and that he communicates them in a compelling style that I envy. But I disagree with his interpretation of the facts.
Now we’re getting somewhere.
Dr Carlat restates Whitaker’s thesis that the steep rise in psychiatric disabilities over recent years has coincided with a similar rise in psychiatric meds prescriptions. Yes, this is true, Dr Carlat agrees, but “correlation does not imply causation.” To say that med use has actually caused the disability, as Whitaker claims, is a stretch. There are other factors involved, Dr Carlat says, including:
There are more psychiatric disorders to diagnose - 297 in the current DSM, about the same as the DSM-III-R from 1987 (at 292), a bit more than the DSM-III of 1980 (at 265), a lot more than the DSM-II of 1968 (at 182), and a whole lot more than the DSM-I of 1952 (at 106). Dr Carlat contends that “the rise in diagnosis has been largely driven by changes in disease classification and subsequent training - not by toxic medications.”
Dr Carlat also notes that because there are more treatments available, doctors have more of an incentive to make a diagnosis. In other words, doctors are not inclined to make a diagnosis for something they cannot treat.
Then Dr Carlat mentions the obvious: That a major reason for the rise in psychiatric disabilities probably has to do with the changed status of psychiatric disabilities. Eligibility has been expanded, thresholds lowered.
To expand on Dr Carlat, a whole disability industry has grown up to facilitate a normally arduous application process. Clinicians and social workers routinely advise even good prognosis patients that they may qualify for disability. A fairly new specialty of disability lawyers is there to assist. Both political parties are more than happy to play along, as those on disability are not counted as being unemployed.
To tie this into a bow: Dr Carlat offers his views by way of “interpretation” rather than “repudiation.” Whitaker may not have shown cause and effect, but neither did he. Instead, Dr Carlat is presenting credible alternatives, supported by his own set of facts. This is the way to make a case.
Let’s forget for the time being whose arguments are more credible. One thing we can all agree on is at last we have a discussion going, something Whitaker wanted all along. Finally, a discussion, not a Nierenberg hissy fit.
More to come ...
Tuesday, February 8, 2011
Whitaker vs Quack Psychiatry - Part II
In yesterday’s piece, I reviewed earlier posts here on Robert Whitaker’s 2010 “Anatomy of an Epidemic,” which presents a well-reasoned argument in support of the proposition that over the long term psychiatric meds may worsen - not improve - the course of mental illness. On January 13, Whitaker delivered a grand rounds to Mass General, using chapter six of his book, “A Paradox Revealed,” to make his case.
Chapter six features a 15-year study by Martin Harrow of the University of Illinois. The study was meant to identify good prognosis schizophrenia patients likely to benefit from from being weaned off their antipsychotics, but Whitaker interpreted the hard data to support his own conclusion that the patients not on antipsychotics in the study fared way better over the long haul than those on antipsychotics in all subgroups, even the bad prognosis patients.
According to Whitaker’s account of his ground rounds, prominent researcher Andrew Nierenberg of Harvard would then “share his perspective” (in the words of the grand rounds invitation) following Whitaker’s presentation.
Dr Nierenberg was one of the principal investigators of the NIMH-underwritten STEP-BD bipolar trials of the mid-2000’s and was also involved in its sister STAR*D depression trials. STEP-BD found that only one in three patients got well and stayed well on their meds over two years while STAR*D found that only one in four achieved a similar result over one year on their antidepressants.
I have heard Dr Nierenberg deliver very insightful talks at various American Psychiatric Association annual meetings, one in which he challenged the doctors in the audience to actually measure if their patients’ symptoms improved, noting they were likely to be in much worse shape than imagined.
I had occasion to talk with Dr Nierenberg in early 2007, at an NIMH-sponsored one-day conference on child bipolar in Maryland, just outside Washington DC. I was seated in an outside foyer, sipping coffee, reviewing my conference materials prior to the first session, when Dr Nierenberg took a seat next to me and graciously introduced himself. He had recently taken over as Director of the NIMH follow-up to STEP-BD, The Bipolar Trials Network.
I recall mentioning to Dr Nierenberg that it would be great if we could follow the STEP-BD patients over the next 20 years to see what happened, sort of equivalent to a Framingham study. Dr Nierenberg enthusiastically agreed. Alas, funding-funding ...
Naturally, I was looking forward to Dr Nierenberg’s response to Whitaker. On his Mad in America site, Whitaker had his own account of the response, plus downloads to Nierenberg’s slide presentation. I skimmed Whitaker’s account very briefly, then went straight to the slides.
What I saw was extremely disconcerting. From the first slide, Dr Nierenberg - or, rather his evil twin - signaled that he was not there to “share his perspective.” Rather, his presentation read, “A Refutation of The [sic] Anatomy of an Epidemic.”
Then came a Merriam Webster definition of refute, “to prove wrong” or “show to be false or erroneous.”
Stupid-stupid-stupid. Two slides in and Dr Nierenberg was already acting oppositionally defiant, with no intention of engaging in a learned and constructive dialogue. Then came a slide with a definition of repudiate. Then a pic of Sarah Palin with the caption, “repudiate.”
Was Dr Nierenberg actually comparing Whitaker to Sarah Palin? Then a Krugman quote with the word “ignorant." Was Dr Nierenberg referring to Whitaker as ignorant? Other slides portray Whitaker as being stuck in a dark ages Cartesian dualist mindset.
Ad hominem attacks of this nature are in extremely bad taste. They are also extremely unprofessional. They also feed into the stereotype of the arrogant and bullying psychiatrist who prefers lashing out to listening.
It gets worse. Further on in the slide presentation, Dr Nierenberg refers to the Harrow study as “retrospective.” Wrong - dead wrong. The study is “prospective,” which is a much higher standard than retrospective. The first sentence to the study abstract explicitly states it is a prospective study.
If Dr Nierenberg can’t even read a study abstract correctly, then, obviously, he cannot be entrusted to read the labeling to the meds he prescribes to patients. In all likelihood, Dr Nierenberg did not take the time from his very busy schedule to carefully read Whitaker’s book, much less think about it, choosing instead to hand off the assignment, together with his rebuttal, to a graduate assistant.
This type of thing goes on all the time in academia.
There are various ways of interpreting the Harrow study, and Dr Nierenberg - or his ghost writer - offers the predictable one of the patients in the study going off their meds as likely to be more well in the first place than those who stay on their meds. But this is neither a refutation nor a repudiation. Moreover, the actual data in the study most unequivocally supports Whitaker’s interpretation.
If Dr Nierenberg or any other expert is able to come up with an argument discrediting the Harrow study, we need to hear it. We really do. And it needs to be done in a thoughtful way that doesn't insult our intelligence.
(An excellent review of the Harrow study is presented by an anonymous patient blogger on Ruminations on Madness.)
Almost out of desperation, Dr Nierenberg came up with a study of a Chinese population that was not even on the point. It gets even more bizarre. Although Whitaker did not bring up antidepressants in his talk, Dr Nierenberg decided to refute and repudiate chapter eight of his book dealing with long-term antidepressant treatment. But the study Dr Nierenberg cited was not a long-term study. Yes, it tracked patients over 25 years, but the actual trial merely tested for dose efficacy over the short term.
It was as if Dr Nierenberg told his assistant, Dig up a study - any study.
What is totally weird is that the best long term trial data on antidepressants - one that shows a dismal result that supports Whitaker - comes from the very STAR*D trial that Dr Nierenberg himself was involved in.
Early in his “refutation,” Dr Nierenberg served up population statistics to rebut Whitaker’s claim of an epidemic in psychiatric disabilities, coinciding with steep rises in psychiatric prescriptions. I’m sure a crack epidemiologist could challenge Whitaker on this, and I would love to hear from one. I will compassionately spare you from Dr Nierenberg’s embarrassing presentation.
This is Dr Nierenberg’s final slide.
Really, this is sick - very sick.
Chapter six features a 15-year study by Martin Harrow of the University of Illinois. The study was meant to identify good prognosis schizophrenia patients likely to benefit from from being weaned off their antipsychotics, but Whitaker interpreted the hard data to support his own conclusion that the patients not on antipsychotics in the study fared way better over the long haul than those on antipsychotics in all subgroups, even the bad prognosis patients.
According to Whitaker’s account of his ground rounds, prominent researcher Andrew Nierenberg of Harvard would then “share his perspective” (in the words of the grand rounds invitation) following Whitaker’s presentation.
Dr Nierenberg was one of the principal investigators of the NIMH-underwritten STEP-BD bipolar trials of the mid-2000’s and was also involved in its sister STAR*D depression trials. STEP-BD found that only one in three patients got well and stayed well on their meds over two years while STAR*D found that only one in four achieved a similar result over one year on their antidepressants.
I have heard Dr Nierenberg deliver very insightful talks at various American Psychiatric Association annual meetings, one in which he challenged the doctors in the audience to actually measure if their patients’ symptoms improved, noting they were likely to be in much worse shape than imagined.
I had occasion to talk with Dr Nierenberg in early 2007, at an NIMH-sponsored one-day conference on child bipolar in Maryland, just outside Washington DC. I was seated in an outside foyer, sipping coffee, reviewing my conference materials prior to the first session, when Dr Nierenberg took a seat next to me and graciously introduced himself. He had recently taken over as Director of the NIMH follow-up to STEP-BD, The Bipolar Trials Network.
I recall mentioning to Dr Nierenberg that it would be great if we could follow the STEP-BD patients over the next 20 years to see what happened, sort of equivalent to a Framingham study. Dr Nierenberg enthusiastically agreed. Alas, funding-funding ...
Naturally, I was looking forward to Dr Nierenberg’s response to Whitaker. On his Mad in America site, Whitaker had his own account of the response, plus downloads to Nierenberg’s slide presentation. I skimmed Whitaker’s account very briefly, then went straight to the slides.
What I saw was extremely disconcerting. From the first slide, Dr Nierenberg - or, rather his evil twin - signaled that he was not there to “share his perspective.” Rather, his presentation read, “A Refutation of The [sic] Anatomy of an Epidemic.”
Then came a Merriam Webster definition of refute, “to prove wrong” or “show to be false or erroneous.”
Stupid-stupid-stupid. Two slides in and Dr Nierenberg was already acting oppositionally defiant, with no intention of engaging in a learned and constructive dialogue. Then came a slide with a definition of repudiate. Then a pic of Sarah Palin with the caption, “repudiate.”
Was Dr Nierenberg actually comparing Whitaker to Sarah Palin? Then a Krugman quote with the word “ignorant." Was Dr Nierenberg referring to Whitaker as ignorant? Other slides portray Whitaker as being stuck in a dark ages Cartesian dualist mindset.
Ad hominem attacks of this nature are in extremely bad taste. They are also extremely unprofessional. They also feed into the stereotype of the arrogant and bullying psychiatrist who prefers lashing out to listening.
It gets worse. Further on in the slide presentation, Dr Nierenberg refers to the Harrow study as “retrospective.” Wrong - dead wrong. The study is “prospective,” which is a much higher standard than retrospective. The first sentence to the study abstract explicitly states it is a prospective study.
If Dr Nierenberg can’t even read a study abstract correctly, then, obviously, he cannot be entrusted to read the labeling to the meds he prescribes to patients. In all likelihood, Dr Nierenberg did not take the time from his very busy schedule to carefully read Whitaker’s book, much less think about it, choosing instead to hand off the assignment, together with his rebuttal, to a graduate assistant.
This type of thing goes on all the time in academia.
There are various ways of interpreting the Harrow study, and Dr Nierenberg - or his ghost writer - offers the predictable one of the patients in the study going off their meds as likely to be more well in the first place than those who stay on their meds. But this is neither a refutation nor a repudiation. Moreover, the actual data in the study most unequivocally supports Whitaker’s interpretation.
If Dr Nierenberg or any other expert is able to come up with an argument discrediting the Harrow study, we need to hear it. We really do. And it needs to be done in a thoughtful way that doesn't insult our intelligence.
(An excellent review of the Harrow study is presented by an anonymous patient blogger on Ruminations on Madness.)
Almost out of desperation, Dr Nierenberg came up with a study of a Chinese population that was not even on the point. It gets even more bizarre. Although Whitaker did not bring up antidepressants in his talk, Dr Nierenberg decided to refute and repudiate chapter eight of his book dealing with long-term antidepressant treatment. But the study Dr Nierenberg cited was not a long-term study. Yes, it tracked patients over 25 years, but the actual trial merely tested for dose efficacy over the short term.
It was as if Dr Nierenberg told his assistant, Dig up a study - any study.
What is totally weird is that the best long term trial data on antidepressants - one that shows a dismal result that supports Whitaker - comes from the very STAR*D trial that Dr Nierenberg himself was involved in.
Early in his “refutation,” Dr Nierenberg served up population statistics to rebut Whitaker’s claim of an epidemic in psychiatric disabilities, coinciding with steep rises in psychiatric prescriptions. I’m sure a crack epidemiologist could challenge Whitaker on this, and I would love to hear from one. I will compassionately spare you from Dr Nierenberg’s embarrassing presentation.
This is Dr Nierenberg’s final slide.
Really, this is sick - very sick.
Monday, February 7, 2011
Whitaker vs Quack Psychiatry - Part One
On Jan 13, 2011, journalist Robert Whitaker, author of “Anatomy of an Epidemic,” delivered a grand rounds at Mass General (which is affiliated with Harvard). Originally, Whitaker was to speak for about 40 minutes, with leading psychiatric researcher Andrew Nierenberg following with his 10-minute shared “perspective.” Then, the organizers decided to allot about 30 minutes each to the two speakers.
Background
Whitaker’s "Anatomy of an Epidemic," which came out early in 2010, makes a well-reasoned case for why psychiatric meds over the long term may significantly worsen - rather than improve - the course of mental illness. A “well-reasoned case” is hardly the same as an airtight argument, but nonetheless demands a very high level of respect.
The book placed heavy emphasis on two pieces of research:
The first, by Guy Chouinard of McGill University, pointed to the possibility of “supersensitivity psychosis” from abrupt discontinuation (or lowered doses) of antipsychotic meds, analogous to rebound symptoms observed in other classes of drugs.
In the second, Whitaker interpreted findings by Martin Harrow of the University of Illinois to indicate that over the long term, patients with schizophrenia who went off their meds had far better outcomes than patients who stayed on their meds.
Taking these studies together, along with other supporting evidence, Whitaker concluded that long-term administration of psychiatric meds is likely to result in structural changes to the brain that greatly worsens symptoms and sabotages any hope of recovery. This argument goes much further than the standard critiques involving meds and those who prescribe them.
My Blog Critiques
Over the course of October and into November, I ran about 10 or 11 pieces based on “Anatomy of an Epidemic,” and also a post-book observation from Whitaker that cited a very recent piece from Giovani Fava of the University of Bologna pointing to the possibility of “oppositional tolerance” to antidepressants.
The gist of my pieces was that Whitaker had basically made his case, which is not the same as saying I agreed with Whitaker. I carefully examined all the studies he cited, plus other research, and concluded there were other ways of interpreting the Choinard and Harrow and Fava findings, namely:
In my pieces, I did take Whitaker to task for failing to cite these studies in their proper context and without recognizing that there were other ways of looking at the evidence. I also cited him on a number of moving violations such as his over-reliance on antipsychiatry sources and his gratuitous cheap-shots of advocacy organizations (such as NAMI) who actually get off their asses and do things.
But I also added my unambiguous concurring voice to his $64,000 question, namely: Why do patients often seem to get worse on psychiatric meds rather than better?
Tying This Into a Bow (for Now)
As I said in the beginning of this piece, Whitaker makes a “well-reasoned” case. It is hardly airtight, but it is a far more compelling one than the extremely specious arguments that psychiatry advances for us having to stay on meds (particularly at high doses) the rest of our lives.
But even if one thinks that Whitaker is off-base, the only answer to a “well-reasoned” argument is another well-reasoned argument. Reason, even in opposition, sheds light and moves the discussion forward. We all benefit - patients, loved ones, researchers, clinicians.
What we do not want to see are petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues. Our well-being is way too important for any psychiatry thought-leader - one who has taken an oath to do no harm - to even consider such a thing.
Next: A psychiatry thought-leader delivers petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues.
Background
Whitaker’s "Anatomy of an Epidemic," which came out early in 2010, makes a well-reasoned case for why psychiatric meds over the long term may significantly worsen - rather than improve - the course of mental illness. A “well-reasoned case” is hardly the same as an airtight argument, but nonetheless demands a very high level of respect.
The book placed heavy emphasis on two pieces of research:
The first, by Guy Chouinard of McGill University, pointed to the possibility of “supersensitivity psychosis” from abrupt discontinuation (or lowered doses) of antipsychotic meds, analogous to rebound symptoms observed in other classes of drugs.
In the second, Whitaker interpreted findings by Martin Harrow of the University of Illinois to indicate that over the long term, patients with schizophrenia who went off their meds had far better outcomes than patients who stayed on their meds.
Taking these studies together, along with other supporting evidence, Whitaker concluded that long-term administration of psychiatric meds is likely to result in structural changes to the brain that greatly worsens symptoms and sabotages any hope of recovery. This argument goes much further than the standard critiques involving meds and those who prescribe them.
My Blog Critiques
Over the course of October and into November, I ran about 10 or 11 pieces based on “Anatomy of an Epidemic,” and also a post-book observation from Whitaker that cited a very recent piece from Giovani Fava of the University of Bologna pointing to the possibility of “oppositional tolerance” to antidepressants.
The gist of my pieces was that Whitaker had basically made his case, which is not the same as saying I agreed with Whitaker. I carefully examined all the studies he cited, plus other research, and concluded there were other ways of interpreting the Choinard and Harrow and Fava findings, namely:
- Supersensitivity psychosis is a valid hypothesis - and clearly there is a compelling need to prioritize this research - but even those working in the field acknowledge it is virtually impossible to distinguish a drug-effect rebound psychosis from an illness-effect psychosis. Choinard’s answer to supersensitivity psychosis was not to wean patients off of these meds (a conclusion easy to make from reading Whitaker) but to keep patients on their meds using smarter strategies (such as adding a mood stabilizer to the mix).
- The purpose of the Harrow study was to identify types of patients with schizophrenia (say those with prior work histories) most likely to do well going off their meds, which is very different than the type of standard long-term clinical efficacy trial that Whitaker led us to believe in his book. The Harrow study identified these populations, and his findings point to a much smarter way of treating schizophrenia than current practice.
- Fava’s “oppositional tolerance” thesis (which parallels Choinard’s supersensitivity psychosis) is very compelling, but there are many other reasons for explaining the very poor long-term results from antidepressants, such as doctors handing out these meds like candy to individuals who never should be on them in the first place.
In my pieces, I did take Whitaker to task for failing to cite these studies in their proper context and without recognizing that there were other ways of looking at the evidence. I also cited him on a number of moving violations such as his over-reliance on antipsychiatry sources and his gratuitous cheap-shots of advocacy organizations (such as NAMI) who actually get off their asses and do things.
But I also added my unambiguous concurring voice to his $64,000 question, namely: Why do patients often seem to get worse on psychiatric meds rather than better?
Tying This Into a Bow (for Now)
As I said in the beginning of this piece, Whitaker makes a “well-reasoned” case. It is hardly airtight, but it is a far more compelling one than the extremely specious arguments that psychiatry advances for us having to stay on meds (particularly at high doses) the rest of our lives.
But even if one thinks that Whitaker is off-base, the only answer to a “well-reasoned” argument is another well-reasoned argument. Reason, even in opposition, sheds light and moves the discussion forward. We all benefit - patients, loved ones, researchers, clinicians.
What we do not want to see are petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues. Our well-being is way too important for any psychiatry thought-leader - one who has taken an oath to do no harm - to even consider such a thing.
Next: A psychiatry thought-leader delivers petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues.
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