Fort and the Three-Leaf Clover

Book III in the series ...

In the land of Ar, on the eve of day of the Festival of the Indecisive Moon of Indeterminate Phase, Fort Maker of Fine Hardwood Didgeridoos hastened into the village, breathless with excitement.

“A three-leaf clover!” he shouted exultantly. “I found a lucky three-leaf clover!”

The villagers, although evincing postures of apostolic confusion, smiled knowingly. The wise Fort, Sage of Ar, was up to his old tricks. Festival-goers from afar, however, unfamiliar with the ways of Fort, only saw a raving old fool.

“A lucky three-leaf clover, petunia feathers!” declared Arigoth of Bor, employing the term of utmost disdain of his land. 

“Indeed,” responded Fort in apparent agreement.

“Everyone knows that it is the four-leaf clover that is lucky,” Arigoth persisted, extending his arms in a great clatter of jewelry.

“Hmm,” responded Fort, scratching a sore on his flesh through a hole in his garment. A crowd now gathered about the two men.

“Is that all you have to say for yourself?” mocked Arigoth, with a great rustling of silk.

“I beg your indulgence,” Fort responded with utmost deference. “You are a man of high import. Alas, I am a man of little account.”

“For once, you speak with great veracity,” Arigoth replied, feeling very proud.

“If only my words could serve me as admirably all the time,” allowed Fort. “Perhaps you can take pity upon this babbling old fool, and we can settle this matter amicably and expeditiously.”

By now, a considerable crowd had gathered.

“Proceed,” said Arigoth, feigning great magnanimity.

“If you would be so kind,” said Fort, holding up his three-leaf clover, “as to show me your four-leaf clover?” 

***

The wise man knows when to quit while he is behind. So said Fort on many occasions, and the crowd, knowing this, turned expectantly to the man from Bor. But Arigoth, hailing from afar and thus unfamiliar with the Sage of Ar, pressed his case: “What four-leaf clover?” the man expectorated with great contempt. “Everyone knows that four-leaf clovers scarcely exist.”

“Yes, yes,” Fort readily agreed. “Why then, do we pin our hopes on that which scarcely exists?”

The crowd politely roared with approval. The man from Bor, however, set his face in a grim countenance, demanding an explanation. The Sage of Ar was happy to oblige. “Behold the three-leaf clover,” he exclaimed, holding it aloft, “abundant and available. Behold my luck.”

This was too much for the man from Bor. “Lucky?” he erupted, unable to contain himself. “You, lucky?”

The crowd turned expectantly to Fort.

“Perhaps,” Fort acknowledged in a quiet voice, “I have not used my three-leaf clover wisely.” He plucked an abundant and available three-leaf clover from the ground and offered it to the man. “If you would be so kind as to show me how to make proper use of this?”

The man expressed puzzlement. “You mean make a wish?” he asked, accepting the clover.

“Yes,” said Fort. “Make a wish.”

“That’s easy,” said Arigoth, twirling his clover. “I wish for a twelve-fold increase in my wealth.”

“And your wisdom?” asked Fort.

“If you persist, and my wisdom,” said Arigoth.

“And a larger - ahem - personal endowment?” asked Fort.

The man made a gesture to strike down this impudent fool, but then, assaying the sentiment of the crowd, decided otherwise. “The size of my personal endowment is fine,” he responded with a great lack of authority.

“Indeed,” demurred Fort with great sincerity. “I have no reason to question either your endowment or your credibility. Please, allow me to continue.”

“Granted,” said Arigoth, with a great rattling of jewelry.

“Perhaps you can clear my confusion. Even in men of substantial personal endowment, is it not natural to wish for - a little bit more?”

“A little bit more,” the man conceded. “That is a perfectly natural wish.”

The crowd nodded in sympathy. Yes, they agreed. A little bit more was a perfectly natural wish.

“Let me see if I got this right,” said Fort. “You are wishing upon your three-leaf clover for a twelve-fold increase in your wealth, a proportionate increase in your wisdom, and - a little bit more?”

“That is correct,” said Arigoth.

Fort affected to ponder the matter. “That is asking a lot of a clover with but three leaves. You already appear to be a man of substantial wealth and wisdom. Perhaps you would choose to limit yourself to one wish?”

“So be it,” said the man impatiently.

“A little bit more?” prompted Fort with great delicacy.

“A little bit more,” the man acknowledged.

“Ah” said Fort. “A wish very worthy of a person of your stature. Woe is me, for I fear I wish most unwisely.”

“Judging by your appearance, I have no reason to dispute you,” the man responded. “Do, pray tell, satisfy my curiosity,” he continued in a mocking voice. “What would be your wish?”

Fort did not hesitate. “A crust,” he responded with great enthusiasm, holding up his clover. “A crust from the loaf in your sack. Would you be so kind as to indulge an old fool his wish?”

“What kind of a stupid wish is that?” replied the man, flinging him a crust.

Fort nibbled on his crust, head down, affecting deep thought. Then he stopped nibbling, and looked up, eyes staring straight into the seat of the man’s endowment. “My wish has been granted,” he said in a voice that carried into the far reaches of the crowd. “Do pray tell, satisfy my curiosity. How did your wish turn out?”

Book I: The Book of Fort

Book II: The Two Wise Old Fools

Didgeridoo Festival!

I recently returned from three weeks off the grid. Four days of it was spent sharing a tent with my special someone at a didgeridoo festival deep in the Oregon woods.

In the film business, they call this an establishing shot.

We woke up to the sounds of this babbling brook running past our tent - and to didgeridoos and drums. We fell asleep to same.

Another establishing shot.

Chad Butler, cool didge guy, who has been organizing this event since 1996.

Will Thoren, another cool didge guy, pioneer of the drop octave/multi-drone technique.

Beneath the didge tree, merrily honking away on my didge.

More cool didge guys, trying out sticks. On the second-to-last day of the festival, I went on record as resolving not to buy a new stick.

Famous last words. The next day I buy this new stick.

Scenes From the Pacific Northwest

Above, McMan Central, off the grid. Below, surrounding evergreens, near Mt Shasta.
Below, water close-up, near Mt Shasta.
Below, two of Mt Shasta.
Below, two of the Oregon Coast

Below, four of the giant redwoods.



Below, tree close-up, Mt Lassen.
Below, waterfall, northern CA.

Back on the Grid

Everybody needs beauty as well as bread, places to play in and pray in, where nature may heal and give strength to body and soul. – John Muir

I'm back from three weeks of being off the grid in the Pacific Northwest. Here I am, in the vicinity of Mt Shasta, playing my didgeridoo in the mountain stream I camped out by for five days. Then up the coast to Oregon and inland into the forest primeval for four days of a didgeridoo festival, then down to northern CA for some redwoods.

One of the most profound experiences of the trip was my first night in the woods, 8,000 feet up in the Sierras, listening to pure silence. No wind, nothing. Not even the footfall of an insect.

Nature does not change us so much as help restore us to our true essence, uncorrupted by the craziness we mistake for reality. The challenge in stepping back into the craziness is to keep intact at least a piece of what we know is real.

Maybe, then, we can deal with the craziness.

My first priority coming back from nature was to change the subtitle of this blog. "Musings in Mental Health," it used to read when I started Knowledge is Necessity at the end of 2008. In the context of what I was writing about back then, the subtitle reflected a shift from my much narrower focus on mood disorders.

But really it was all about "From God to Neurons." Last year, I incorporated the phrase as part of a long subtitle. Now it's a solo act.

Knowledge is Necessity has always been about ruthless self-inquiry. Mental Health is only part of the picture. God to neurons is the true scope. As I wrote in the second piece I posted here:

Life is about first impressions - a voice, a sight, an aroma - and how we filter and ultimately link them. Often, we fail to see how the dots connect. Life is like that. Life, basically, is a first draft.

Over time, we acquire wisdom and insight. We become better people. We learn to find a measure of joy and peace of mind. But we also know that nothing is permanent. That life has a way of reducing us to nothing.

Next thing, we're groping frantically, looking for new dot to connect ...

Here I am, out of the woods, still connecting dots. 

***

Many thanks to all of you who have shared my journey over the years. We're all in this together. Let's keep exploring ...

Forget the Whittaker Sideshow: Tom Wootton is the Main Event

I’m taking a brief time-out from not posting any pieces here to briefly comment on something I just read by Tom Wootton on Psychology Today. As many of you know, Tom is the founder of “Bipolar in Order” and the author of “The Bipolar Advantage” and other short books, one of which I reviewed a couple of years ago as “the worst piece of crap ever assembled between two covers.” 

But what’s a little minor nitpicking between friends right? When Tom actually sticks to writing what he knows, he is the most visionary and astute mind out there. Trust me, Robert Whitaker is a sideshow. Love him or hate him, Tom is the person we need to be paying attention to, and his recent piece Why I Am Against Meds (the title is a gimmick to get you to read the piece) affords a timely reminder.

First, Tom observes what we already know - that the pro-meds and anti-meds positions are poles apart, to the point where everyone is shouting and no one is listening. This can get pretty frustrating, especially if you’re in the business - as Tom is - of shedding light rather than heat on the topic. Listen to Tom:

At the end of my talks I am frequently accosted by members of one camp or both. It is pretty clear that neither side even heard what I said and the only thing they listened for is whether I took their side in the only thing that matters to them. I didn't validate their extreme point of view and they are furious with me.

He goes on to say:

If you visit the sites that are anti-med or anti-psychiatry it is mostly about what they are against and not about better outcomes. They are not talking about getting bipolar in order. They are talking about their opposition to a set of tools. They are fixated on meds and psychiatry instead of gaining understanding about how to function while manic or depressed.

But he doesn’t have very good things to say about pro-meds extremists either:

Medicine can help moderate the intensity during the freedom stage of bipolar in order, but they cannot get you in order by themselves. The role of medication becomes more peripheral as one moves through freedom stage to stability and is largely irrelevant once one reaches self-mastery. There is no point in taking something to lower the intensity when intensity is no longer an issue.

A little background here: Tom is a strong advocate of experiencing the full emotional range of what he characterizes as our “condition.” Imagine being able to enjoy all the advantages of “up” (the creativity, productivity, sociability, etc) without fear of going off the rails. Even “down” has its upside - depression is very conducive to introspection and a lot of deep thinking. So imagine - and this is a tough sell - maintaining a healthy state of down.

In short, if we are seeking “normal” as an outcome, we are squandering our gifts. Instead of viewing bipolar “disorder” as something we wish would go away, we should think of getting our bipolar “in order.” We can have our ups and downs. Expect to struggle with them, but also expect to be challenged to thrive, not just survive.

If you are new to this and are confused, that’s okay. You are probably used to hearing the standard pro-and-anti-meds party lines. Tom, by contrast, is challenging us to think, daring us to grow and become better people in the process. That’s what it’s all about, isn’t it?

The other stuff. It’s a distraction, a loser’s game.

Whitaker, Torrey, and Dopamine Supersensitivity: The Conversation Continues

This is the fifth in our series of pieces dealing with Fuller Torrey’s response to Robert Whitaker’s 2010 “Anatomy of an Epidemic.” I’m sure by now you have all had enough, but bear with me. We are learning - all of us - and there is no better way to shake issues loose than by closely observing and then analyzing the back and forth exchange between two of the most prominent voices in psychiatric treatment.

In my coverage of this debate, I am less concerned by who is right and who is wrong than in what we all stand to learn. Nowhere does this come in more loud and clear than on the topic of dopamine supersensitivity.

Whitaker makes reference to the phenomenon in Chapter Five of “Anatomy of an Epidemic,” where he (thankfully) demolishes the myth of “chemical imbalance of the brain.” Contrary to the impression your doctor may lead you to believe, the brain is not some sort of chemical soup that gets thrown out of whack by too much or too little serotonin or dopamine. Likewise, the brain is hardly restored to balance by tinkering with these chemical levels.

In essence, when it comes to an illness such as schizophrenia or addictions such as to cocaine, we find ourselves less concerned with “how much” dopamine is in the brain than in “how sensitive” the brain is to dopamine. The same applies to depression and serotonin.

The presynaptic neuron (the one you always see to the left or at the top on any given diagram) tends to get all the attention, as this is the neuron that releases neurotransmitters into the synapse - the gap - separating the other (postsynaptic) neuron on the left or the bottom. Below is a screenshot from an old Zoloft TV commercial. Here, you see a depressed brain with a “chemical imbalance,” with hardly any neurotransmitters in the synapse:

Now, thanks to Zoloft, we see neurotransmitters bursting out of “Nerve A” like nauseated passengers frantically disembarking from a Kenny G cruise. The swarm is headed straight toward a presumably receptive “Nerve B.” where we are left to assume a happy ending.

But wait. How truly receptive is Nerve B? Ah, that is the real question.

In chemical imbalance terms, if depression is about “too little” serotonin, schizophrenia is about “too much” dopamine. But how much is too much? We turn our attention to “Nerve B.” Whitaker in “Anatomy” (p 76) picks up on the action:

Having discovered that dopamine levels in never-medicated schizophrenics were normal, researchers turned their attention to a second possibility. Perhaps people with schizophrenia had an over-abundance of dopamine receptors. If so, the postsynapic neurons would be “hypersensitive” to dopamine, and this would cause the dopaminergic pathways to be overstimulated.

Whitaker goes on to say that in 1978, University of Toronto researcher Philip Seeman (pictured above) announced that this was indeed the case. Autopsies revealed that the brains of those with schizophrenia had 70 percent more D2 receptors than normal. Nevertheless, Whitaker notes that Seeman cautioned that the “long-term administration” of first-generation antipsychotics may have been the cause, not the schizophrenia.

Here, Whitaker frustratingly breaks off the natural flow of the narrative. Whitaker is pursuing his own agenda, but Dr Seeman, who has devoted his life to the study of dopamine receptors, has an entirely different story to tell, one we need to hear, in his own words, on his own terms. A 2007 article he wrote in Scholarpedia, “Dopamine and Schizophrenia,” best explains:

The discovery in the 1950s that the sedative drug chlorprozamine had both an antipsychotic effect and Parkinsonian side effects (such as tremors) led in the 1960s to a dopamine hypothesis for schizophrenia. By 1967, researchers were discussing “overstimulation of dopamine receptors” as a possible cause for schizophrenia, but it took until 1975 to identify the dopamine D2 receptor as the binding site of dopamine and antipsychotics.

According to Dr Seeman, citing a number of studies, in first episode patients who have never been treated with antipsychotics the density of D2 in the frontal cortex and striatum is elevated by 10 to 30 percent. These same patients experience decreases in D2 in other areas of the brain, as well as decreases in D1 receptors throughout the brain.

D1 and D2 do not operate in isolation. The decreases in D1 may switch a high-affinity D2 receptor into a low-affinity one (ie one not conducive to binding).

Here is the money quote from Seeman’s piece:

Because antipsychotics, including aripiprazole and bifeprunox, alleviate psychosis by inhibiting D2, it indicates that psychosis is associated with a hyper-dopamine state.

Dr Seeman goes on to explain the need for focussing on “how sensitive” rather than “how much.” In experiments involving the administration of low doses of stimulants, three-quarters of those with schizophrenia experienced psychosis or worsening psychosis, even when on an antipsychotic, as opposed to zero to a quarter of the control subjects. In Seeman’s words:

The data indicate that dopamine supersensitivity is prevalent in patients with schizophrenia.

Seeman describes a number of animal studies that suggest a variety of causes for schizophrenia and psychosis, including different gene variations, brain lesions, birth hypoxia during Caesarian section, stimulants, and steroids. All these result in dopamine supersensitivity. Rats given high doses of corticosterone, for instance, showed a 210 percent increase in D2 high-affinity receptors.

Dr Seeman also notes, citing studies by Chouinard, that “antipsychotic drugs themselves can occasionally induce an increase in the high-affinity state of dopamine D2 receptors and the associated state of behavioral dopamine supersensitivity.” Withdrawal of the antipsychotic, he explains, can unmask this dopamine supersensitivity and precipitate an episode of “supersensitivity psychosis.”

Chouinard’s findings of supersensitivity psychosis is where Whitaker comes back into the picture, to make his case for the harmful effects of the long-term administration of antipsychotics. But to make that case, Whitaker first needs to acknowledge the general principle of dopamine supersensitivity.

In other words, the best working theory we have for schizophrenia and psychosis at the moment has to do with study findings showing increases in dopamine D2 high-affinity receptors in key parts of the brain in rats and in humans. As Dr Seeman notes, there may be multiple causes and multiple gene variations for schizophrenia and psychosis along multiple neural pathways, but just about all of these have a way of “converging onto a similar set of brain D2High targets.”

Whitaker’s response? Three way out of context quotes (p 77). First:

“The dopaminergic theory of schizophrenia retains little credibility for psychiatrists.” This came out of the blue in a 1990 article by French researcher Pierre Deniker. The article actually acknowledges the “anti-dopaminergic action” of antipsychotics, but cautions against a one-size-fits-all approach to treatment.

Second:

There was “no good evidence for any perturbation of the dopamine function in schizophrenia.” The 1994 article that houses this quote, from John Kane of the Long Island Jewish Medical Center, actually talks up the newer generation atypical antipsychotics, with their putative (and still not proved) action on the serotonin system.

Finally:

“There is no compelling evidence that a lesion in the dopamine system is the primary cause of schizophrenia.” Whitaker’s use of this 2002 quote (Steven Hyman, former NIMH head) is supposed to lend weight to the proposition that chemical imbalance is a myth. But all Hyman is saying is what everyone agrees on: That schizophrenia, like all other mental illnesses, is heterogenous and multifactorial - many shapes and sizes, many different causes.

Hopefully, you see the point: One cannot talk up supersensitivity psychosis while trying (pathetically, at that) to discredit dopamine supersensitivity. To do so invites fierce attack by Fuller Torrey.

Next: Fuller Torrey attacks ...

Whitaker vs Torrey: Crunching Numbers

This is the fourth in our series of pieces dealing with Fuller Torrey’s response to Robert Whitaker’s 2010 “Anatomy of an Epidemic.” In his review, Dr Torrey asserts that on matters of schizophrenia and antipsychotic drugs, “Whitaker got it mostly wrong.” The same day that Torrey published his review, Whitaker in a blog post issued an angry rebuttal and his own counter-attack.

In our most recent installment, we discussed Whitaker’s heavy reliance on a 2007 publication of a Harrow-Jobe 15-year longitudinal study which found that about 40 percent of schizophrenia patients did well when taken off their antipsychotic medication. What the authors of the study found of greater significance, however, was the fact that the patients who did well were those with a “good prognosis” to begin with.

In his book, Whitaker made the barest passing reference to Harrow’s real findings, neither reporting on the primary results of the study nor how this information can be used to help patients with schizophrenia achieve better outcomes. Rather, Whitaker interpreted the study to mean that “that the drugs worsened long-term outcomes” (p 118).

Had this been a long-term trial of antipsychotics as Whitaker would have us believe, the authors would have conducted an entirely different study. There would have been at least two evenly-matched groups of patients, one on antipsychotic meds and one not on antipsychotic meds, if not at the very beginning of the study then at a key stage further along.

The catch is long-term studies of this type are impossible to conduct. The costs are prohibitive and no review board would dare permit such an enterprise. But the real world affords untold opportunities to observe the natural course of schizophrenia without meds. As Torrey scathingly notes:

[Whitaker] fails to focus any attention on the fact that on any given day in the United States half of all individuals with schizophrenia, or about one million people, are not being treated. This is a huge natural experiment to test his thesis. Many of these individuals are found in public shelters, sleeping under bridges, in jails, and in prisons. If Whitaker had spent more time in these settings observing the outcome of this natural experiment, instead of delivering lectures on his vision of the impending antipsychotic apocalypse, he would have written a very different book.

In this regard, Whitaker’s highly selective use and non-use of information becomes a major issue, akin to writing “Gone with the Wind” without noting that there is a Civil War going on.

So, is there any legitimacy to Whitaker interpreting the Harrow study his own way? Yes. It’s called “secondary analysis,” a fairly common practice amongst researchers and journalists. Basically, one mines other people’s data in search of new - and often startling - insights. And Whitaker certainly had more than enough data to work with.

The 2007 Harrow-Jobe article tells us that 12 of 64 patients with schizophrenia (19 percent) experienced a period of recovery over 15 years. Of these: Eight of 12 (40 percent) were no longer on any meds and two of five were on meds but no longer on antipsychotics.

In contrast, only two of 39 patients (5 percent) on antipsychotics experienced a period of recovery. Moreover, 19 of 23 patients (83 percent) with uniformly poor outcomes after 15 years were on antipsychotics. Tellingly, 64 percent of these patients had psychotic activity at the 15-year point vs only 28 percent not on antipsychotics.

Harrow’s numbers back up Whitaker, right? Wrong. Recall, the Harrow study involved an apples-to-oranges comparison - good prognosis patients vs bad prognosis patients. The good prognosis patients, identified at the beginning of the study, were the ones most likely to get better in the first place and therefore were in a position to go off their meds.

For Whitaker’s secondary analysis to work, he would have had to show that the “good prognosis” patients who stayed on antipsychotics did worse than the good prognosis patients who went off antipsychotics. (It would have been useful to compare results in the bad prognosis group, as well, but this finding wouldn’t have had the same significance, as we don’t have high expectations for this group.)

So - we’re looking for an apples-to-apples comparison. Easy to show, right? We just pull up the relevant number and ...

No number. Whitaker doesn’t cite one. No problem. We’ll find the number in the 2007 Harrow-Jobe study that Whitaker refers to. Wait, this is weird. The number isn’t in the study, either. The authors slice and dice the data in a multiplicity of ways, but the closest they come to what we’re looking for is a finding that 17 percent of the good prognosis patients were on antipsychotics after 4.5 years and 13 percent after 15 years.

No mention of how these particular patients actually fared. Why? The answer is simple (okay, complicated for me). Let’s assume one-third of the patients in the study were good prognosis patients. Let’s make the number 20. If only 13 percent of these patients were on antipsychotics at the 15-year mark, we are looking at a study sample of two, at most three, patients.

A three-patient sample? Okay, let’s be generous and double it. A six-patient sample?

In his blog, Whitaker insists that “in every subgroup of patients (by prognostic type), those off medication had better long-term outcomes (in the aggregate).” In making his claim, Whitaker relies upon this paragraph from Harrow-Jobe:

In addition, global outcome for the group of patients with schizophrenia who were on antipsychotics was compared with that for the off-medication schizophrenia patients with similar prognostic status. Starting with the 4.5-year follow-ups and extending to the 15-year follow-ups the off medication subgroup tended to show better global outcomes at each follow-up.

Had Whitaker actually asked, “how much? how many?” he would have realized the absurdity of his assertion.

Conclusion: Whitaker’s secondary analysis fails. Totally, absolutely, completely. Case closed, right? Not so fast:

When the dust settles, we still have two key pieces of data that simply will not go away: Eight in 12 patients not on meds (plus two of five on meds but no antipsychotics) experiencing periods of recovery vs only two of 39 on antipsychotics.

Still a very small sample size. Still apples-to-oranges. Still other factors in play such as the type of life experience and personal make-up that separates good prognosis from bad prognosis patients.

But when all is said and done, Whitaker is perfectly justified in saying: “Hey, hold on a minute, have a look at these figures.” And we need to be listening.

Likewise, Torrey is perfectly correct in insisting that Whitaker got it wrong. Again, we need to be listening.

More to come ...

Previous Whitaker vs Torrey pieces:

At Last, a Conversation

Collision Course

Digging Deeper

Whitaker vs Torrey: Digging Deeper

This is the third in our series of pieces dealing with Fuller Torrey’s response to Robert Whitaker’s 2010 “Anatomy of an Epidemic.” In his review, Dr Torrey asserts that on matters of schizophrenia and antipsychotic drugs, “Whitaker got it mostly wrong.” The same day that Torrey published his review, Whitaker in a blog post issued an angry rebuttal and his own counter-attack.

Previously, we examined Whitaker’s use of two studies he cited in support of his thesis that mental illness is on the rise because of psychiatric medications rather than despite them.

In the first instance, Torrey busted Whitaker for blatantly misrepresenting one study’s findings. The study involved a mere passing reference, but was illustrative of the highly selective cherry-picking that Whitaker employs throughout his book. Whitaker counter-attacked, accusing Torrey of “dishonesty,” but failed to answer the charge.

In the second instance, Torrey dismissed two WHO studies that Whitaker heavily relied upon, characterizing them as “discredited.” Essentially, Torrey (citing various researchers) interprets these studies as an apples-to-oranges comparison. The studies (which found better outcomes among the third-world patients surveyed) - serve as a textbook example of why no finding can be taken at face value. Basically, both Torrey and Whitaker were justified in interpreting these studies the way they did. It would have been helpful, however, had Whitaker addressed Torrey’s apples-to-oranges issue. Instead, he issued another gratuitous “dishonesty” charge.

Let’s move on ...

The Harrow-Jobe Study

Whitaker’s Position

This 15 (later 20)-year longitudinal study, published in 2007, served as Exhibit A in Whitaker’s case against antipsychotic medications. In his book, Whitaker interprets the study results to advance his claim that patients with schizophrenia fare worse on meds over the long-term than those not on meds. According to Whitaker (p 115):

...The off-med group began to improve significantly, and by the end of 4.5 years, 39 percent were “in recovery” and more than 60 percent were working. In contrast, outcomes for the medication group worsened during this thirty-month period. ...

Whitaker in his book did note that Harrow in an interview attributed better outcomes to “stronger sense of self” and “better personhood,” but Whitaker did not elaborate why these factors were significant. Instead, he kept his focus exclusively on meds vs non-meds.

Later in his book (p 311), Whitaker accuses both the NIMH and NAMI of failing to promote (and by implication suppressing) the study’s optimistic finding:

... I also searched the NMIH and NAMI websites for some mention of the studies listed above and I found zilch. ... Forty percent of those off medications recovered over the long term! But that finding directly contradicted the message that NAMI has promoted to the public for decades ...

Torrey’s Response

In his review, Dr Torrey points out that the Harrow-Jobe study is not exactly the hot news that Whitaker makes it out to be. Since at least as far back as 1938, Torrey reports, numerous schizophrenia outcome studies have found that “on average one-quarter of the patients recovered completely, one-quarter had a continuous illness, and the other half had intermediate outcomes between these two extremes.”

Of critical importance, citing one researcher: “There are relatively benign and malignant forms of illnesses generally diagnosed as schizophrenia.” This leads to what the study was really all about, with Torrey noting that “Harrow et al. even explicitly state that their study provides no evidence on whether very long-term use of antipsychotic medication produces undesirable effects for some SZ [individuals with schizophrenia].”

Once again, we have an apples-to-oranges issue. As I observed in a number of previous blog posts, rather than comparing a meds group to a non-meds group as we are used to seeing in clinical trials, the study actually compared a “good prognosis” group to a “bad prognosis” group. These patients were identified at the beginning of the study, then followed over 15, then 20 years.

Predictably, the good prognosis group had better results, with more of them in a position to go off their antipsychotics and to function well. But, according to Torrey, Whitaker twisted these findings to serve his own purposes:

Using tortured logic, he asserts that the Harrow et al. study proves that long-term antipsychotic use causes brain damage and is responsible for many of the symptoms of schizophrenia, when in fact the study does nothing of the kind.

Whitaker’s Comeback

In his blog post, Whitaker breaks down those parts of the Harrow-Jobe study that showed how all the subgroups of non-medicated patients fared better without antipsychotic medications. This includes both “good prognosis” patients and “bad prognosis” patients. Says Whitaker:

Although [Harrow] didn’t provide the global data for these two subtypes, he did report this finding: “In addition, global outcome for the group of patients with schizophrenia who were on antipsychotics were compared with the off-medication schizophrenia patients with similar prognostic status. Starting with the 4.5-year followup and extending to the 15-year follow-up, the off-medication subgroup tended to show better global outcomes at each follow-up.”


In other words, in every subgroup of patients (by prognostic type), those off medication had better long-term outcomes (in the aggregate).

Whitaker (predictably) assigns another “dishonesty moment” to Torrey. This is based on the fact that Whitaker did not cite the Harrow-Jobe study for the proposition “that long-term antipsychotic use causes brain damage and is responsible for many of the symptoms of schizophrenia,” as Torrey claimed. Rather, Whitaker kept his interpretation to outcomes.

Nevertheless, Whitaker in his book (p 118-119,) linked the Harrow-Jobe study to a study that did suggest that “drugs made patients more vulnerable to psychosis over the long-term,” and (p 120) he noted that “we can also see how this drug-induced chronicity has  contributed to the rise in the number of disabled mentally ill."

What Harrow et al Actually Say

From a 2005 article (free on PubMed):

More recent data of ours suggest that some of the schizophrenia patients who go off antipsychotics are a different type of patient. They have better premorbid developmental achievements, have more favorable prognostic characteristics, and are more resilient and less vulnerable to psychopathology (or “healthier”), leading to their better functioning.

And from the 2007 article Whitaker refers to (you have to pay $50 for this, the abstract is free):

The results suggest that the subgroup of schizophrenia patients not on medications was different in terms of being a self-selected group having better earlier prognostic and developmental potential.

And the key finding from the wider dataset (including patients with other diagnoses), in a 2009 article (available free on PubMed):

A more external locus of control is related to fewer periods of recovery, to both depressed mood and psychosis, and to various aspects of personality.

Locus of control (LOC) “refers to the extent to which an individual perceives events in his or her life as being a consequence of his or her actions, and thus under his or her perceived control.” Internal LOC is good. External LOC is bad.

Of the schizophrenia patients in recovery over 15 years, according to the 2009 article, 67 percent had internal LOC. In the overall sample, 75 percent had internal LOC.

Basically, Harrow et al are telling us that an individual’s personal make-up is a key predictor to recovery, perhaps THE key. In their study, these were the patients more likely to go off their meds and do well off their meds. In the authors’ own words (2007):

Patients who are internally orientated and have better self-esteem are the types of patients who are more likely, if their functioning improves, to urge that they try functioning without medications ...

This is worth restating: According to Harrow et al, based on their study findings, doctors should be encouraged to consider taking a good prognosis patient who is doing well off his or her meds. This is an entirely different proposition than what Whitaker would have us believe - namely, get EVERYONE off their meds as soon as possible.

Whitaker doesn’t say this in so many words, but the thrust of his interpretation of the study  - namely “that the drugs worsened long-term outcomes” (p 118) - leaves himself open to Torrey’s charge of using “tortured logic.”

What Whitaker is doing is making a “secondary analysis,” a common and legitimate practice that can often yield far more interesting insights than the primary analysis. The catch is that you have to read Whitaker’s book microscopically to know he is making this of kind analysis. He certainly does not trumpet Harrow et al’s real findings, much less explain them, and this is disturbing, to say the least.

This brings us to the crucial question, does Whitaker’s secondary analysis hold up?

To be continued ... 

Collision Course: Whitaker vs Torrey

This is the second in a series of pieces dealing with Fuller Torrey’s response to Robert Whitaker’s 2010 “Anatomy of an Epidemic.” In his review, Dr Torrey asserts that on matters of schizophrenia and antipsychotic drugs, “Whitaker got it mostly wrong.”

My first piece laid out the background to the controversy, namely my view (spread across numerous pieces throughout 2010 and 2011) that Whitaker had not made his case that psychiatric meds have caused a mental illness epidemic. Nevertheless, he made a very strong “case to answer,” one that demands a considered point-by-point response, preferably from a leading psychiatrist. More then two years went by since the publication of “Anatomy,” with no signs of intelligent life from psychiatry. Last week, Torrey broke the silence. Better late than never.

The same day that Torrey published his review, Whitaker in a blog post issued an angry rebuttal that cited Torrey for at least four instances of “dishonesty,” as well as using the occasion to attack Torrey and the Treatment Advocacy Center for its aggressive stance on assisted outpatient treatment (which a good many of us - myself included - also have serious issues with).

Lost in the noise was that on key points Whitaker has failed to respond to Torrey’s criticisms. Let’s get started:

The 1994 Outcome Study

Whitaker’s Position:

In the foreword to his book, Whitaker says that he “encountered two research findings that didn’t make sense.” One of these was a 1994 study conducted by researchers at Harvard, which found that “outcomes for schizophrenia patients in the United States had worsened during the past two decades ...”

He says no more about the study and makes no further mention of it in the rest of his book.

Torrey’s Response:

In his review, Dr Torrey notes that what the study actually said was “quite different,” namely that when a broad definition of schizophrenia was in vogue, outcomes were a lot better. Moreover, “the data showed a clear improvement in outcomes during the 1960s and 1970s following the introduction of antipsychotic drugs.” Outcomes worsened during the 1980s and 1990s, “which the authors attributed to the introduction of a narrow definition of schizophrenia.”

The broad and narrow definitions are no mere diagnostic quibbling. The narrow (DSM) version (introduced in 1980) mandates six months of symptoms.

Torrey also noted that Whitaker “later added that the worsened outcomes were due to the use of antipsychotic drugs.”

Whitaker’s Comeback:

In his blog post, Whitaker claims that he only mentioned the study in passing in the foreword to his book, as something that “piqued my curiosity,” thus implying that his use of the study was not worthy of Torrey’s attention. Surprisingly, in his defense, Whitaker acknowledges that the study authors said exactly what Torrey said they said, namely:

... the researchers reasoned that improved outcomes in the middle part of the century were due to both a change in diagnostic criteria that broadened the definition to include patients who were less ill at disease onset and then to the introduction of neuroleptics.

Then Whitaker served up his own theory of why maybe - sort of - the study supports his thesis anyway. (We won’t get into that here.)

Torrey’s big mistake? Whitaker made no specific reference to this study when he talked about worsened outcomes on antipsychotic medications, as Torrey stated in his review. This brought down Whitaker’s wrath in the form of “dishonesty moment number one" for Torrey.

Actually, though, on page 118 of his book, Whitaker says, “We have followed the trail of documents to a surprising end ...” Why wouldn’t we assume the Harvard study was part of that paper trail?

Verdict:

Dishonesty moment to Whitaker, big time. This is an egregious example of a journalist misciting a study to serve his own ends, then conveniently forgetting about it when the actual facts failed to support his thesis. This is hardly the only example of Whitaker’s highly selective cherry-picking in his book. Torrey was perfectly correct to call out Whitaker.

As for Torrey’s “dishonesty moment,” using a flimsy pretext to brand a critic as dishonest violates all the basic principles of playing well with others.

Finally, Whitaker totally failed to address Torrey’s extremely relevant point concerning broad and narrow diagnostic criteria. More about that, coming right up ...

The WHO Outcome Study

Whitaker’s Position:

Whitaker devotes considerable attention in his book to two World Health Organization studies that found that those with schizophrenia in developing countries had much better outcomes than those in developed nations. As Whitaker reported in his book (p 111):

... the bottom line is clear: In countries where patients hadn’t been regularly maintained on antipsychotics earlier in their illness, the majority had recovered and were doing well fifteen years later.

Whitaker then goes on (p 119) to link this study to other studies to conclude that “evidence for long-term recovery rates are higher for nonmedicated patients appears in studies and investigations of many different types.”

Torrey’s Response:

Dr Torrey in his review evinces far less enthusiasm, noting that the WHO study claim “has continued to be criticized over the years and has now been largely discredited.” At issue, once again, is broad and narrow diagnostic criteria. Citing various sources, Torrey notes that many of those enrolled in the third world centers probably did not have true schizophrenia (some of the patients were referred by religious and traditional healers). More likely, the researchers were dealing with a good number of those suffering from “acute reactive psychosis,” which have much better outcomes than schizophrenia.

Torrey also cites a five-year 2011 study on a cohort of Ethiopian patients with findings that contradict the WHO studies. Finally:

Faced with such criticisms, the authors of the WHO studies have recently modified their claims, stating that “we do not argue that the prognosis of schizophrenia in developing countries is groupwise uniformly milder” and acknowledging that “the proportions of continuous unremitting illness…did not differ significantly across the two types [developed and developing] of setting.”

Whitaker’s Comeback:

Predictably, Whitaker assigns Torrey another “dishonesty moment.” This is based on the fact that far from “modifying their claims,” the authors of the WHO studies in the same paper Torrey cited actually vigorously defended their findings. Says Whitaker:

Dr. Torrey, in his review, was intent on discrediting the findings from this WHO study, which reported superior outcomes in poor countries where only a small percentage of patients were regularly maintained on antipsychotics. To do so, he implied that the WHO investigators now agreed with the critics of the study, when that is not true.

Verdict:

We have a big wet loogie on the table, which Whitaker fails to address, namely: The authors of the WHO studies have explicitly acknowledged that the patients in the third-world countries had a milder prognosis than those in the developed countries. Why is this important? If we are comparing apples to oranges, then the findings of the WHO study are totally meaningless.

More likely, the “apples to oranges” controversy merely raises questions about the study rather than discredits it, as Torrey maintains. If anything, the WHO study is a textbook example of why no finding can be taken at face value. Certainly, we all know this when it comes to clinical trials sponsored by drug companies.

What is particularly disturbing is that Whitaker would have been aware of the “apples to oranges” controversy when he wrote "Anatomy of an Epidemic." Yet he makes only a fleeting reference to it in his book, and only in the context of vindicating the first WHO study (as if there were no reason to question the second study). A straightforward and thorough stating of the controversy would hardly have undermined both studies' findings or Whitaker’s thesis. If anything, preemptively dealing with this concern would have greatly strengthened Whitaker’s argument, along with his credibility.

Instead, we are left with the feeling that Whitaker is hiding something.

Keep in Mind ...

In past blog posts, I have been supportive of Whitaker, but I have also not hesitated to point out numerous examples of where he played fast and loose with the facts, or where - quite frankly - he failed to turn in his homework. I continue to be supportive of Whitaker, but I also support any critic of Whitaker acting in good faith. In my 13 years researching and writing on mental illness, one vital lesson stands out loud and clear: Never - never-ever-ever - take anyone (and I include myself here) at face value. Always maintain a healthy skepticism, even if the party involved claims to be speaking for you - especially if the party involved claims to be speaking for you.

To act otherwise is to place your life on the line. Our illness takes no prisoners.

Much more to come ...  

Torrey Responds to Whitaker: At Last, a Conversation

I have devoted considerable space on this blog to Robert Whitaker’s 2010 “Anatomy of a of an Epidemic,” which posits that mental illness is on the rise because of psychiatric medications, rather than in spite of them. In reviewing Whitaker, I read the same studies he cited in his book and came to the conclusion that Whitaker had not made his case.

Nevertheless, I pointed out that Whitaker had made a very strong “case to answer.” In other words, until someone (presumably a psychiatrist with weighty credentials) made a convincing counter-argument (preferably in a point-by-by rebuttal), Whitaker’s thesis - whatever one’s misgivings - stood as the authority.

I also stated that Whitaker had initiated a conversation that we badly need to have. Whitaker was also very clear that he wanted to have this kind of discussion.  

To my dismay - and to the shame of psychiatry - that conversation never eventuated. Daniel Carlat of Tufts University in two blogs issued what was essentially a collegial light dusting, taking issue with Whitaker’s presentation of the evidence in a friendly sort of way, but hardly knocking any holes in his main arguments.

Andrew Nierenberg of Harvard purported to “rebut” and “refute” Anatomy of an Epidemic in response to a grand rounds Whitaker delivered at Mass General. The so-called rebuttal amounted to an irrational and high-volume hissy fit (one punctuated by totally unprofessional ad hominem attacks) that I could only characterize as “sick, very sick.”

A few commentators quibbled about Whitaker’s interpretation of the term, “Epidemic,” tossing in an ad hominem attack or two for good measure, but otherwise avoiding engagement.

That all changed last week with an article posted on the website of the Treatment Advocacy Center. Anatomy of a Non-Epidemic - A Review by DrTorrey, read the heading. “How Whitaker Got it Wrong,” read the subheading.

E Fuller Torrey (pictured above) has a way of getting a rise out of certain mental health advocates. Dr Torrey is the founder of the Treatment Advocacy Center (TAC), which pushes for aggressive outpatient treatment laws for those with severe mental illness. The issue is a hot-button one, and TAC and Torrey have come under considerable criticism for their position and their tactics (including from this writer).

But Torrey has paid Whitaker the ultimate compliment of intelligently and thoughtfully responding to Whitaker. Too often, in our focus on personalities, we lose sight of the issues. Advocates who should know better have elevated Whitaker to the status of cult hero who can do no wrong. This is a grave disservice to both Whitaker and the people we purport to serve.

Torrey, too, enjoys a certain cult following, particularly among first-generation NAMI parents, as well as villain status from a host of mental health advocates. We will discuss these matters in a future blog. But, for right now, let’s focus on the issues. Essentially, Torrey has shifted the whole discussion. He has convincingly answered Whitaker’s “case to answer.” This hardly means that Torrey is right and Whitaker is wrong. Indeed, a constructive synthesis would move the discussion to a new level, one that Whitaker and Torrey could easily agree upon - the need for some serious research.

In other words, if the scientific evidence is insufficient to either support Whitaker’s case or to rebut it, then let’s put some serious money into unearthing the evidence.

In future blog posts, we will explore point-by-point Dr Torrey’s responses to Whitaker. In the meantime, this disclosure: Dr Torrey wrote a very glowing back-cover blurb for my 2006 book, “Living Well with Depression and Bipolar Disorder.”  The blurb states: “Very helpful for those affected by bipolar disorder and their families ... I recommend this book enthusiastically.”

I have had no other involvement with Dr Torrey and none with the Treatment Advocacy Center.

Stay tuned ...