Monday, November 29, 2010

My First (but By No Means Last) Experience with Online Dating - Conclusion

We pick up on the story in progress ...

Of all things, my brilliantly conceived plan of attracting the right woman based on my "Simon Cowell eliminator" involving the enigma of Einstein's iPod succeeded beyond my wildest dreams. There, mere hours after signing up was a message in my inbox. "Nancy," a classical musician who loved nature and ran triathlons for fun, had expressed interest in me.

Mind you, I had been too stupid to select her, myself. My prefrontal cortex, I learned too late, turned out to be a far better thinker than decider. To make a decision, it needed input from the emotional regions of the brain, and - alas! - my strongest emotion proved to be fear. That is, until I came across "Tomatoe Girl," a woman with no obvious interests who couldn't spell tomato but proved to be boneriffic.

Our only reason on earth is to make God laugh, and by now He was snorting milk out his nose. Here was the catch: Any future with Nancy in it demanded the same reaction in my brain as I had with Tomatoe Girl. Okay, it didn't have to be right away, but something had to happen. Sparks had to fly. Nancy clearly had soulmate potential, and her photos revealed a very lovely and thoughtful woman. But boneriffic?

We arranged to meet on Thursday for breakfast overlooking La Jolla Cove in San Diego. This was the mandatory "coffee date." She stepped out of her car, a vision of loveliness. She looked apprehensive and I assured her she didn't have to worry about passing any audition. We would be seeing more of each other, I let her know. She breathed easy, and the relationship was on. We began talking and couldn't stop. We continued our conversation along the beach, checking out the seals and other marine life. All too soon, it was time to go. We made a date to see each other Sunday.

We wound up at the end of the pier on Imperial Beach, sipping beer and eating fish tacos. The dolphins cooperated by putting on a show beneath us. So did the moon as we strolled the beach arm in arm. An attraction was growing.

Tuesday was to be a low-key date. Some afternoon outdoor recreation, then an early night. We rented a kayak and I amazed her by demonstrating I was not an out-of-shape spaz. Apparently, this sort of thing matters to triathloners, triathletes, whatever. Later, over beers on an outdoor patio, in the middle of one of our now-signature nonstop conversations, time froze. There she was, talking. Then, there she was talking in slow motion, with the sound muted. The patio and everything around her changed into a blur, and there was only her, just her. That was when it registered:


Suddenly, I was back in fast motion on a noisy outdoor patio with a mad urge to send glasses and plates crashing to the concrete as I took her in my arms and threw her on the table in a passionate embrace.

"Can we have a little privacy, please?" I would admonish the startled patrons.

A slow-motion camera on my face would have revealed an explosion of give-away micro-expressions that are visible in real time only to trained observers. For all I know, my eyes popped out of their sockets and my tongue rolled to the floor like a character in a Don Martin cartoon, but to everyone on the patio I was just a guy with his date, sipping beer.

I managed to maintain my sense of perfect equipoise all the way to her driveway. There, I lost my equipoise. Our relationship was about to turn romantic.

It stayed that way for three months, and it seemed like it would go on forever, but it didn't. One dark sleepy Monday morning, I walked out her front door. I didn't realize it would be for the very last time. Nothing left to say.

Previous installments
Part I
Part II
Part III

Sunday, November 28, 2010

My First (but By No Means Last) Experience with Online Dating - Part III

The story so far: I had just signed up at on online dating site, only to discover my prefrontal cortex, which is nominally in charge of my thinking, had turned the assignment over to another part of my anatomy.

"Boneriffic!" my dopamine-sensitive ventral tegmental area (VTA) was screaming. For the purposes of this essay, all you need to know about the VTA is that this is the part of my brain where my dick has a branch office. As you will recall, I had worked out a brilliant strategy of making an intelligent choice from a long list of very good looking active and intelligent women based on my "Simon Cowell eliminator" that had to do with the enigma of Einstein's iPod.

Trust me, it was a brilliant strategy.

Then I discovered that my prefrontal cortex is only capable of weighing and measuring, but not deciding. For that, it needs input from the emotional areas of the brain. Unfortunately, my amygdala - fear central - was in league with my hippocampus and other centers of ancient memory, cranking out malicious sound bites for the amusement of my inner mother.


Suddenly, I was that short skinny nerdy high school kid with glasses at my first high school dance, on the gymnasium floor, Bobby Vinton's "Blue Velvet" crackling out of a crappy PA system, trying to summon the nerve to ask Marie Kapinsky to dance.

"Loser!" my prefrontal cortex concurred, with unassailable prosecutorial authority. The brief it had assembled was bullet-proof. The men these women date, the thinking part of my brain reminded me, own their own homes. They drive in cars with Bose Surround Sound.

But I don't want to die a virgin! was my best defense. Okay, that wasn't exactly accurate, but I was stalling for time. In desperation, I summoned "Tomatoe Girl," the woman with no obvious interests who couldn't spell tomato.


Instantly, the tenor of the conversation changed. My dick was now in charge, with my VTA calling the shots. My amygdala and its henchmen were nowhere to be found.

She doesn't know how to spell tomato, my prefrontal cortex reminded me.

And that's why she won't complain when I show up in a car that doesn't have a working radio, my same (and now dueling) prefrontal cortex shot back.

Weighing, measuring, weighing, measuring ...

Nothing good ever came from thinking with your dick, my dueling prefrontal cortex let me know.

True, my dueling prefrontal cortex acknowledged. Bad marriages, failed relationships. I needed to change my pattern. In some way I couldn't comprehend but knew was true, Tomatoe Girl was part of my old pattern. On the other hand:

Who is the woman I want to be snuggled up with on the sofa right now?

Shit-shit-shit! This was crazy. The tide had turned. My entire prefrontal cortex was now in thrall to my VTA. Already, it was cooking up images of the two of us - me and Tomatoe Girl - curled up in a comfortable corner of her motor home (the corner that didn't need to be jacked up), sipping Jack Daniels from the same bottle and viewing reruns of "Dancing with the Stars."

"The sheriff won't show up till tomorrow," she whispers in my ear. "In the meantime, we have tonight."

I have a very good friend and mother confessor in LA, who I reveal all my dark secrets to. "Sometimes I want to drive down to San Diego and wring your neck," she is wont to let me know.

But it was no use. I was already composing a message that entirely contradicted everything on my profile. Hopefully Tomatoe Girl will just ignore me, I rationalized as I clicked "send." But I also walked away from my computer knowing I had broken the deadlock, that I had overcome my fear and insecurities and had set the process in motion. Tomorrow was another day.

Something told me to check my computer one more time. A fresh email informed me a new message was waiting in my online dating site inbox. She was a classical musician who loved nature and entered triathlons for fun. Not only that, she read the same books I did and had solved the enigma of Einstein's iPod.

"Holy shit!" I could only think. Could this be the one? 

To be continued ...

Previous installments
Part I
Part II

Friday, November 26, 2010

My First (but By No Means Last) Experience with Online Dating - Part II

The story so far: I had just signed up for an online dating site, but was having trouble making up my mind. We pick up on the action ...

By now, I was scrutinizing the photos with the intensity of a CIA analyst, desperately searching for visual clues, trying to give my brain something to work with. We are told that looks matter far more to men than to women. My answer to this is if I looked like George Clooney I wouldn't have to spend so much time thinking about what to put in my profile. Yes, looks do matter to men, but not in the way women think they matter.

A few years ago, I entertained (but not very seriously) the idea of starting up a new magazine, "Boneriffic." If we're going to have fake superficial standards for female beauty, I figured, then it made no sense that those who are incapable of getting it up for women should be the deciders. What dickless wonder, for instance, came up with the brilliant idea that vulnerable teen-age girls are supposed to mature into womanhood  with high-strung cadavers as their role models?   

It's not about physical dimensions or specs, and men know this. Women are their own harshest critics. Women: If you don't believe me, just listen to your own conversations. Trust me, if men said the same things about women that women say about women, there would be no new generation left on earth to even discuss the topic of sexual attraction.

You see a fellow member of your gender - a potential competitor in life's ultimate prize - and you say something like her eyes are too close together. We see the same human being, the manifestation of all things possible, and say it's a good day to be a bicycle seat.

It all comes down to the simple fact that men are wired to get boners, and for once Darwin and the Bible are in precise accord. So, back to my magazine, "Boneriffic." Real men, real boners. I would publish photos sent in by truck drivers of their sexy wives and girlfriends. Not only that, I would recruit these same truck drivers as designers for a whole new Boneriffic fashion line. Think Victoria's Secret meets LL Bean.

So, anyway, here I was, just signed up on my online dating site, my carefully plotted out strategy laid waste by the unexpected operational limitations of my prefrontal cortex. It could think, but it couldn't decide, not without some input from the part of the brain where emotions reside. Enter the midbrain's dopamine-sensitive ventral tegmental area (VTA). Rats whose VTAs get stimulated with an electrical current get erections and start mounting the nearest available female.

This is the part of the brain (the right VTA) that also lights up with humans in love, anthropologist Helen Fisher of Rutgers University reported in a lecture at the 2004 American Psychiatric Association’s annual meeting. (Simultaneously, the fear-mongering amygdala goes silent.) Romantic love, she went onto say, is a "drive" rather than an emotion, a "need" that compels one to seek a specific mate. Technically, testosterone/estrogen-driven lust (the craving for sexual gratification) is separate, as is oxytocin/vasopressin-influenced attachment (the sense of calm one feels with a long-term partner), but the three are also connected.

"Don’t copulate with people you don’t want to fall in love with," Dr Fisher cautioned, "because indeed you may do just that."

All kinds of emotions are in play, but they exist in relationship to the various drives, depending on how the eternal lust-love-attachment tango is playing out. The prefrontal cortex is also participating - assembling data, putting information into patterns, making strategies - but one gets the impression as a very junior partner. Case in point:

My brain was gridlocked. On paper, there was little to distinguish Prospective Soulmate #1 from Prospective Soulmate #2 from Prospective Soulmate #36. Which one? The mountain-biking attorney who loves to cook or the nature mystic small business owner who spends her time off raising autism awareness? Maybe it was the one who actually subscribed to - not just purchased as plane reading - "The New Yorker." But which one was she? The scuba diving emergency room nurse or the equestrian special education teacher?

I needed visual cues. The eyes have it - something that looked straight into my soul and locked in. A zillion and one things you can't explain, that would translate into a feeling or intuition, that would provide the prefrontal cortex with food for thought, that would help me make up my mind. I'd been at this since early afternoon and it was now approaching one in the morning. I'd set myself the modest goal of initiating contact with at least one prospect before going to bed and time was running out.

"Tomatoe Girl!" something in my head cried out. The one with no obvious interests who couldn't spell tomato. My prefrontal cortex had eliminated her in the opening minutes of the first round, but something in my midbrain was demanding a rehearing. Obediently, I dialed up Tomatoe Girl's profile and checked out her photos, and instantly felt a stirring below the equator. Oh shit, I could only think.

"Boneriffic!" my VTA was screaming. My poor prefrontal cortex didn't stand a chance.

To be continued ...  

Wednesday, November 24, 2010

My First (but By No Means Last) Experience with Online Dating

When my brain isn’t working, it’s a good thing I have a dick to think with. Case in point, some time ago I decided to give internet dating a go. I signed up on a site, then spent the next several hours agonizing over what kind of public face I wanted to display. For instance, would I come across as a snob if I said I read The New Yorker, and if I did let this particular cat out of the bag would I need to disclose that I wasn’t actually a subscriber but only bought it as a plane read?

And what if my soulmate-in-waiting pressed me on this? Then I would have to reveal that I’d only flown once this year, which meant my Scientific American reading was way down, as well.

Online dating is definitely a game of chess, calculating at least four moves ahead, using the best information available to anticipate a future that you have deluded yourself into thinking you can control. The part of the brain responsible is the prefrontal cortex, the seat of reason that separates us from those who believe that Fox News is true and other lower life forms.

But there are limits in our capacity to think things though, which I discovered once I started checking out the available women on this particular dating site. Just about all of them were very attractive. They looked after themselves, kept themselves fit, and did interesting things. Clearly, these women had no room in their lives for losers. What they wanted to hear from me was something along the lines of my love of the smell of the freshly oiled teak of my sun deck as I sat overlooking my private ocean while I broke down my last triathlon on the prototype iDrool that my good buddy Steve Jobs asked me to try out as a personal favor to him.

Fortunately, this culled most of the herd for me, but there were still way too many candidates to choose from. On one hand, I needed to come across as desirable as possible to the whole rest of the pack. On the other, I needed the equivalent of a prick like Simon Cowell to give me four finalists. My profile (which I have fictionalized here) was finally starting to take shape. First, the black box warning:

I'm self-employed, which means my boss is a cheap bastard and my employee a lazy no-good shit.

Then the catnip:

Silence is golden, so is great conversation. Sharing both with the right individual is priceless.

Then my set-up:

I'd love to prepare one of my gourmet pizzas for you ...

And finally my Simon Cowell eliminator:

... while we sip wine and listen to Einstein's iPod.

Perfect, I decided. More people on this planet have "Antarctica" listed as their place of birth than would be able to get what I was driving at by Einstein's iPod. Even I didn't know what the fuck I meant by Einstein's iPod.

It didn't matter. All I had to do was read through the profiles of some likely candidates, contact one or two at a time over the next several weeks, indicate my interest in them, and invite them to check out my profile. The first one who didn't impale herself on my Simon Cowell eliminator, assuming she was interested in me, would be my next coffee date. Let the games begin.

I went to the profiles only to discover my prefrontal cortex refused to cooperate. Shopping for women online is not the same as shopping for kitchen appliances online, or rather, yes it is. I may tell myself that I want a pasta maker that simply works on the same principle as an old-fashioned wringer washing machine, but ultimately I am going to choose the model that fires up my ventral tegmental area (VTA), the dopamine-sensitive region in the midbrain that mediates pleasure and reward.

While the thinking parts of my brain are weighing up customer reviews and performance specs and price points, my VTA is getting a hard-on over the shiniest looking appliance on the page. Through a complex series of brain signaling, the VTA shuts down the amygdala, associated with fear (which the thinking parts of the brain really need to be paying attention to) and starts negotiating with the prefrontal cortex.

Never mind price and practicality, says the VTA in effect. Get the bright shiny one. In a straightforward negotiation, the prefrontal cortex simply abdicates its authority to the VTA. (Yes, get the bright shiny one.) In a more complicated transaction, the prefrontal cortex spins somersaults rationalizing the choice already made by the VTA. (Yes, the bright shiny one is far better value for my money, even though it costs twice as much as the others. Not only that, it's far more efficient, notwithstanding the fact that three reviewers have noted they had trouble anchoring the object to the counter.)

Hopefully, when you unpack your shiny new pasta maker, the handle doesn't fall off. It probably doesn't matter, anyway. You'll use the thing just once, then exile it to the same dark corner of your lower pantry as your way cool retro bread machine.

So my best-laid plans for choosing a woman online were doomed from the start. This is why men get boners. Women, too, in a manner of speaking. The prefrontal cortex is simply incapable of making up its mind. Which woman? The tree surgeon who has just finished reading Joseph Campbell or the martial arts black belt who teaches drama at a community college? Or the woman with no obvious interests who enjoys her "tomatoe" plant?

As I said, good thing I have a dick to think with.

Tuesday, November 23, 2010

Rerun: Misdiagnosis - Patients Tell Their Stories

My recent five-part (and counting) series, Are Antidepressants Bad For You?, noted that a large part of the problem has to do with physicians blindly treating anything that resembles a depression with these meds, often with disastrous results. This piece from a year ago elaborates ...

I write a very different blog on HealthCentral's BipolarConnect. There, I take a backseat to my readers, bipolar patients and loved ones. Nearly a month ago, I asked them:

Were you misdiagnosed with depression or something else? How long did it take before you finally received the correct diagnosis?

Readers began telling their stories over the next days and weeks, which I assembled into three blog pieces. The narrative is sobering and instructional:

"Jane's" response is fairly typical. She was diagnosed with depression at age 16 and prescribed Zoloft, “which was making me like a bunny on mass caffeine consumption.” She was put on Paxil, but her depression worsened and she gained 40 pounds. Unable to hold onto her job, she found a new doc, who “cocked his head, asked about my family’s mental health history ... and asked me ‘Did anyone ever ask you if you thought you might be bipolar?’"

Finally, on Lamictal, she has her life back, but "I spent 11 years on the wrong meds and destroying my life because I was misdiagnosed.”

What is coming in loud and clear is that a misdiagnosis of depression is all too common, with years on antidepressants that only worsen one's unrecognized bipolar. Since we tend to seek help when we are depressed rather than manic, it is not surprising that we receive the wrong diagnosis at first instance. But then the problem is compounded by psychiatrists who refuse to listen. As "Rachel," who waited 14 years for the correct diagnosis, describes it:

My major complaint with this whole debacle is not that I was incorrectly medicated, it is that I was incorrectly medicated because an entire comprehensive mental and physical inventory was never taken. AKA no one ever TALKED to me about what I was feeling and why I was feeling it. No one had mined my data for facts and established a clear pattern of my behavior. The first person who did that was me. ... They didn't do their job. Much like getting a bad mechanic job, my tranny dropped out on the freeway and my vehicle hit the wall going 75 - a complete loss.

Doctors who don't listen - that has been by far the number one complaint I have received from readers ever since I began writing about bipolar more than 10 years ago. As "Lorraine," who suffered with antidepressants for three years, writes:

The doctor (as many are) was a know-it-all and rarely listened to me. The doctor rarely considered how I felt. The doctor thought no one could ever know more than this one. The doctor rarely even considered the possibility of what I was feeling.

Why does it take so long for doctors to get smart? "Georgine" responds: "I believe it was because I was diagnosed with [depression] before so instead of trying to find out what I needed, the docs took the previous diagnosis and just agreed with it."

It took 25 years before a doctor finally corrected the original error.

And this from "Eva":

It was only when I got old and ugly that a doctor finally said, ya man, she's depressed, and she's bipolar. ... When I was young, beautiful and well-groomed, I looked like a female high-powered executive. On top of the world to the doctors who saw me. They dismissed my claims of depression, as ridiculousness. What does she have to be depressed about? Now that I'm old, ugly, unfashionable, I'm believable.

Our own ignorance and denial is another factor. As "Lilly" reports: “I stayed in denial successfully with alcohol and pills.” At last, during her third hospitalization, “I finally opened up a pamphlet on bipolar.” She took her meds as directed, and “was able to see reason. ... I’ve been struggling with this disease for over 25 years since I had turned 16 years old and I was 40 when I excepted it as something I would have to live with and take care of for the remainder of my life. Life is good now.”


There is no substitute for listening to real accounts from patients and loved ones. You can check out the full conversation at Bipolar Connect in the comments to my original question and a follow-up question, as well as my three pieces and the comments to these pieces:

Misdiagnosis - Eight Readers Tell Their Stories

Misdiagnosis - The Dialogue Continues

Misdiagnosis - Readers Tell Their Stories

Thursday, November 18, 2010

Grading Depression

I recently posted a five-part (and counting) series, Are Antidepressants Bad for You? For a good many, the answer is yes. A lot of it has to do with our antiquated diagnostic criteria for depression, which treats virtually all depressions as the same. This encourages one-size-fits all treatments that turn out to fit very few and harm a good many.

In Feb, the American Psychiatric Association released a draft of an updated DSM, which would perpetrate the mistakes of the past. In light of my most recent series, it's appropriate here to re-run three of my critiques in this one post. Without further ado ...

Grading Depression - Part I

This is the first in a series of report cards that grades the homework turned in last week by the DSM-5 Task Force. Our first assignment: Depression.

First, some background ...

According to statistics cited on the NIMH website, major depression is the leading cause of disability in the US and affects 6.7 percent of Americans in any given year. Plus major depression is a major component to bipolar disorder, affecting another 2.6 percent of the US population each year. In addition, dysthymia (major depression lite) accounts for an additional 1.5 percent.

An illness of this dimension literally comes equipped with its own gravitational field. Thus, few psychiatric diagnoses make sense without some reference to depression, be it anxiety or schizophrenia or borderline personality disorder.

This means that if the people responsible for coming up with a new version of DSM depression get it wrong, then the whole document - together with the whole field of diagnostic psychiatry - is going to be out of alignment.

Fortunately, everyone knows what depression is, right? Um, not exactly. Early versions of the DSM recognized the highly complex nature of the illness at the expense of confusing just about everyone and thus influencing no one. The DSM-III of 1980 and its successors (the DSM-III-R, the DSM-IV, and the DSM-IV-TR) went for simplicity and clarity, which seemed to please just about everyone, except maybe patients.

The major knock on depression as we know it is that it is a catch-all diagnosis for all manner of things going wrong. But this is its major appeal, as well. One one hand, not enough patients are getting better on meds and therapies designed to combat this simultaneously mysterious and obvious entity called depression. On the other hand, just enough are.

At issue for the DSM-5’s Mood Disorders Work Group is how these major contradictions can be reconciled.

Time to start grading ...

The symptom checklist

This was a masterstroke from those who brought us the DSM-III. So much so, that we tend to think of the checklist as something that existed since before the dawn of time and that is based on pure science rather than being pulled out of thin air. Even though the current DSM recognizes several different forms of depression, everything originates from this (five of) nine-item menu.

Critics have identified a number of major problems with the list, namely:
  • It is biased toward identifying depression in women rather than men (such as “appears tearful”).
  • It fails to identify the patient’s predominant state of mind. For instance, it is possible to check off “feeling depressed,” followed by “significant weight loss,” “insomnia,” “psychomotor agitation,” and “fatigue.” Voila! Major depression, but what does that tell us? Is one vague mental symptom followed by four physical ones truly depression?
  • It fails to identify the patient’s predominant state of mind (again). Sad? Agitated? Unmotivated? Feeling hopeless? Overthinking things? Excruciating psychic pain? Yes, we know it’s depression. But what is really going on?
On the other hand, the list has been in service for 30 years. It may not be perfect, but it does give us a reasonable approximation of a condition that so profoundly lays waste to so many. So why change it? This was the approach adopted by the workgroup.

Unfortunately, this was the safe option that gave us nothing to think about, that squelched a conversation that we badly need to be having, and that put the interests of monied stake-holders (such as the insurance industry) over the needs of patients.

Grade: F-minus.
Mixed Anxiety Depression

This is a wholly new and separate diagnosis, distinct from major depression. The workgroup recognized that nearly 60 percent of those with major depression also experience anxiety, which adversely affects patient outcomes.

The new diagnosis would acknowledge that one need not experience full-blown major depression or full-blown anxiety to wind up seriously distressed and incapacitated. A little bit of each will do. Thus, Mixed Anxiety Depression calls for just three or four depression symptoms (one which must include either feeling depressed or loss of pleasure), plus “anxious distress” which involves such things as “irrational worry.”

The recognition of anxious-depression is long-overdue, but since it was already listed in the DSM-IV appendix as deserving of future consideration, one cannot give the current workgroup credit for putting the issue on the table. Moreover, there is no mention of how “agitated depression” and other types of “mixed states” may fit into the picture.

Grade: C.

Mixed Episodes

The current DSM only recognizes mixed depression-mania states as occurring in bipolar I, and only in the ridiculously limited context of full-blown mania combined with full-blown depression. The DSM-5 would restore a measure of sanity by acknowledging that mixed states can occur in bipolar II, as well.

How this fits into unipolar depression is unclear. On one hand, the workgroup expressly rules out unipolar depression if the patient had ever experienced a mixed episode. On the other hand,
with no explanation, the workgroup adds the specifier, “with mixed features.” Huh?

There is good evidence that many individuals with unipolar depression experience mania/hypomania symptoms in their depressions, not enough to rate a diagnosis of bipolar, but enough to raise their levels of distress and make their depressions more difficult to treat.

On this very important issue, the DSM-5 workgroup has not handed in its homework.

Grade: Incomplete.

Grading Depression - Part II

Part I began issuing grades on the homework handed in last week by the DSM-5 Task Force concerning its proposed revisions to depression. To recap:

The symptom checklist
- “So why change it? This was the approach adopted by the workgroup.” Grade: F-minus.

Mixed anxiety depression
-  “The recognition of anxious-depression is long-overdue.” Grade: C.

Mixed depression-mania episodes
- “On this very important issue, the DSM-5 workgroup has not handed in its homework.” Grade: Incomplete.

Moving on ...

Chronic and Recurrent Depression

These are two entirely different animals. For the first time, the DSM would fully acknowledge the chronic variety (“chronic depressive disorder” with an episode lasting at least two years). The new diagnosis would subsume dysthymia and change its threshold to include major depression as well as low grade depression.

Gone is the “chronic” specifier to a major depressive episode.

The DSM-IV criteria for recurrent depression would stand, namely two or more major depressive episodes (lasting at least two weeks) at least two months apart. No provision is made, however, for the reality of highly-recurrent depressions that come and go at a faster rate.

Recurrent depression - and the highly-recurrent variety in particular - may have more in common with bipolar depression than unipolar depression, or at least may occupy common ground in dire need of mapping. Somewhere, somehow, on some level, the rather obvious overlap between unipolar and bipolar needs to be recognized and dealt with. On this vital issue, the workgroup looked the other way.

Grade: F.


The DSM-5 Task Force mandated its various workgroups to come up with sophisticated severity measures analogous to assessing hypertension. This would obviate the rather arbitrary and clumsy distinction the current DSM makes between major depression and dysthymia (which the workgroup proposes eliminating).

It also places less emphasis on the symptom checklist. Thus, someone with all nine depression symptoms who is nevertheless able to hold down a job and keep his or her marriage going is in much better shape than someone with only four symptoms who technically does not meet the threshold for major depression but hasn’t been able to get out of bed in six months.

The Mood Disorders  workgroup is currently investigating a variety of measures.

Grade: Incomplete.

The Specifiers

The current DSM uses these to parse out different types of major depression, thus major depression with: psychotic features, catatonic features, melancholic features, atypical features, postpartum onset.

The DSM-5 would leave this list intact with two exceptions. “Chronic” is removed as a specifier and upgraded to a diagnosis, and “mixed features” is added with no explanation. In addition some changes are added to the psychotic features specifier to account for severity as well as type (“congruent” or “incongruent”).

The problem with specifiers in this context is they are only as good as the symptom checklist they are supposed to be specifying. There must be a better way, for instance, of distinguishing an agitated depression from a vegetative one or a mainly sad state of mind from one characterized by the lack of ability to care.

Think of depression as too much emotion on one hand and not enough on the other. Factor in too much or not enough thinking, and you can see that the experts charged with this brief had their work cut out them. They didn’t put in the work.

Grade: F.

Reactive Depression

The DSM-II of 1968 distinguished between what it saw as biologically-based depression (endogenous) and depression seen as a reaction to stressful events (exogenous). The DSM-III and its successors wisely ditched speculating about cause and effect and stuck to categorizing observable symptoms.

Thirty years later, however, advances in brain science suggest some merit in going back to the future, but with this ironic twist: Although current brain science does not yet support diagnostic descriptions based on underlying biology, one can make a good biological case for supposedly non-biological reactive depression.

Not only that, we already know that managing stress is a key to managing one’s depression. Stress Junction is where Freud, brain science, and common sense meet. The DSM-5 workgroup missed the bus.

Grade: F-minus.


Can persistent and treatment-resistant depression be looked upon as a personality disorder? Consider this assignment extra credit. Neither the Mood Disorders nor the Personalities Disorders workgroups took up the challenge.

No grade.

Grading Depression - Part III


Is there a place in your house you dread looking into? The attic? The crawl space? A certain closet? The bottom of your refrigerator? The current DSM contains its own version of the dreaded place. It is called NOS - not otherwise specified - and accompanies 41 listed diagnoses.

The draft DSM-5 would continue the practice. I peeked in and, suffice to say, experienced every traumatic flashback involving attics, crawl spaces, closets, and refrigerators, and then some. Some background:

If you’re a DSM editor and don’t know what to do with a certain type of symptom or behavior, you create an NOS closet (or refrigerator) and stick the weird stuff in and close the door. Maybe you’ll figure out what to do with it later.

It you’re a doctor and don’t know how to diagnose a certain patient, you write up NOS and find the appropriate closet (or refrigerator), shut your eyes, stick it in, and close the door. Maybe you’ll come up with the correct diagnosis later.

The trouble is NOS is a black hole. What, for instance, does “Depression NOS” mean? Imagine “Cardiovascular NOS” and you can see that the practice is unacceptable, whether one is practicing medicine or writing a diagnostic manual. Moreover, the practice is highly abused. A background paper put out by the DSM-5 mood disorders workgroup cited an unpublished study that found that the specialist and nonspecialist clinicians in the sample employed “NOS” in 37-38 percent of their primary diagnoses for depression.

The DSM-5 would change NOS to CNEC (conditions not otherwise classified). I opened the freshly painted closet door to find ...

Subsyndromal depressive CNEC. This would include patients in obvious distress who somehow don’t meet the formal diagnostic criteria for depression. Given the extremely wide view of depression the DSM already employs and its generously low thresholds it’s hard to imagine such a group. Certainly there are those who must put up with residual symptoms once the worst is over, but can’t we find a better way of defining this category? Out in broad daylight?

Major depressive disorder superimposed on a psychotic disorder
. What the hell is something this major doing buried away in a closet?

Recurrent brief depressive disorder
. So THAT’s where they stuck highly recurrent depression! I was looking all over for it. Nope, not out with recurrent major depressive disorder, where it belongs. Nope, not red-flagged as a type of depression closely related to bipolar. Nope, stuck away in a closet.

PMDD. Are you kidding me? We still hide “women’s problems” in the closet?

The sad thing is the things lurking in the DSM-5 CNEC closet are nearly identical versions of those still gathering dust in the DSM-IV NOS refuse bin.

Grade: F-minus

To Sum Up

Thus concludes my three-part DSM-5 Depression Report Card. Here are the subjects and my grades:
  • Symptom Checklist: F-minus
  • Mixed Anxiety Depression: C
  • Mixed Episodes: Incomplete
  • Chronic and Recurrent Depression: F
  • Severity: Incomplete
  • The Specifiers: F
  • Reactive Depression: F-minus
  • Personality (extra credit): No grade
  • NOS: F-minus
Overall grade: F

Concluding Remarks

One of the ironies in issuing this report card is that I owe much to virtually all of the members of the DSM-5 mood disorders workgroup. I have read their articles. I have heard them speak at conferences. I have asked them questions face-to-face. In some cases, I found myself seated at the same breakfast or luncheon or dinner table.

My dealings with these individuals have been extremely productive and beneficial. To a person, they are as dedicated to their work as they have been gracious to me. Moreover, a good deal of what I know about mood disorders can be attributed to them and their colleagues. Many of my key Aha! moments are a direct result of the wisdom they have shared with me, their professional colleagues, and with patients and family members.

So, what went wrong?

For one, DSM-5 operating parameters were far too restrictive, involving an onerous burden of proof for new inclusions. Too often, the necessary empirical data was lacking. We may “know” for instance that depression is bound up in personality, but can we “prove” it?

Scientists need to “validate” their claims with scientific evidence. But what if the picture they produce is inaccurate and misleading and leads to the kind of absurd results I've brought up this series? No acknowledgment of the obvious relation and overlap between depression and bipolar? C'mon!

My concern is with "credibility," which the DSM-5 sacrificed in its obsessive over-pursuit of "validity." As a result, the DSM-5 is failing in its key mission of aligning psychiatric authority to our clinical reality.

Nevertheless, everyone has a stake in the status quo - Pharma, the insurance companies, the clinical-research establishment, perhaps even patient advocacy groups. Credible or not, the DSM pays the bills. Thus, no one is about to stand up and say the DSM-5 is a piece of shit. Okay, I just did, but who listens to me?

The other main problem is “paradigm freeze,” which I will get to in a future blog piece.  

And Finally ...

I don’t want to come across as negative, but my next Report Card grades bipolar, which will also involve liberal use of the sixth letter of the alphabet.

Tuesday, November 16, 2010

Are Antidepressants Bad for You? - Part V

We left off with the proposition that if you walk in the door with depressive symptoms, your clinician has at least four chances to get it wrong and only one chance to get it right. Your condition may be posing as classic depression, but may in fact be something completely different, namely:
  • The depressive phase of bipolar.
  • A highly recurrent depression, having more in common with bipolar than classic unipolar depression.
  • A personality disorder, such as borderline.
  • Your true personality - your "normal" baseline self - rather than an exception to your personality.
Chances are your clinician is missing this. He or she is thinking: Looks like depression, must be depression, ergo antidepressant. But we know that antidepressants can make bipolar worse. Likewise, there is good support for the proposition that people with highly recurrent depression need to avoid them, as well. And even a caveman's dumb half-brother knows that there is no med for changing a personality.

Clearly, most of you reading this should never have been put on an antidepressant in the first place. A placebo would have worked a lot better and with no side effects. At least you wouldn't be feeling worse. But maybe you're one of the "lucky" ones, with classic depression. An antidepressant for depression is just what the doctor ordered, right? Um, uh, define depression. This edited extract from a Feb blog post elaborates:

The DSM-II of 1968 viewed depression as both separate from (in the sense of “depressive neurosis”) and as part of manic-depression (in the sense of “manic depressive illness, depressed type”) and tied into anxiety (in the form of “involuted melancholia” and as the driving force of “neurosis”) as well as embedded into personality (as in “cyclothymic personality disorder characterized by depression”).

Moreover, the DSM-II distinguished between depression seen as a result of the mysterious biology of the brain (“endogenous”) and depression seen to be caused by a reaction to events (“exogenous”).

The DSM-III of 1980 replaced all that with a monolithic view of unipolar depression, separating it out from manic-depression and anxiety and personality and doing away with the endogenous-exogenous distinction. Instead, for the first time, we were treated to the famous and extraordinarily arbitrary nine-item symptom checklist.

In my book, "Living Well with Depression and Bipolar Disorder," I cite a 2004 article by Gordon Parker MD, PhD of the University of New South Wales in support of the proposition that this one-size-fits-all view of depression results in clinical trials that indiscriminately lump all patients together, with no regard to critical distinctions that may spell the difference between success and failure.

We know for instance that an SSRI such as Paxil gets 50 percent of patients with “major depression” 50 percent better over a period of about six weeks. This is good enough for the drug companies, who now have a license to print money, but what about the patients? Who wants a 50 percent chance of success? And who wants to be just 50 percent better?

What do we know about Paxil, anyway? Does it work better on a patient whose depression is marked by sadness? If so, is it possible to target this group of patients? Maybe then we would be seeing 80 percent of these individuals getting 80 percent better.

And try this on for size. Maybe a patient whose main feature is lack of motivation (about which the DSM has nothing to say) would benefit from something else, as would depression brought on by stress (the type of “exogenous” depression axed from the DSM-III). Maybe these drugs don’t exist. Maybe Pharma would be encouraged to develop them. As Dr Parker in a 2007 piece concludes:

Depression is a diagnosis that will remain a non-specific "catch all" until common sense brings current confusion to order. As the American journalist Ed Murrow observed in another context: "Anyone who isn't confused doesn't really understand the situation."


To tie this in a bow: It's not enough that a clinician accurately diagnoses depression, as the term is at best an umbrella designation, the way "infectious disease" is an umbrella designation. Yes, an antibiotic may be useful against many types of infectious disease, but we cannot make the same claim for an antidepressant for the zillion different things going on inside our brains that we happen to lump together as depression. The best we can say for antidepressants is that they work for some individuals with DSM depression. The catch is we don't know in advance who these people are.

More to come ...

Previous articles

Are Antidepressants Bad for You?
Are Antidepressants Bad for You? - Part II
Are Antidepressants Bad for You? - Part III
Are Antidepressants Bad for You? - Part IV 

Monday, November 15, 2010

Are Antidepressants Bad for You? - Part IV

The story so far:

In his blog Mad in America, author Robert Whitaker drew attention to a recently published review article by Fava and Offidani that came to this startling conclusion:

When we prolong treatment [with antidepressants] over 6–9 months we may recruit processes that oppose the initial acute effects of antidepressant drugs (loss of clinical effects). We may also propel the illness to a malignant and treatment-unresponsive course that may take the form of resistance or episode acceleration.

In support of their view, Fava and Offidani cite studies that show that staying on antidepressants longer than three months has no effect at reducing the risk of recurrence and may, in fact, make the illness worse. What may be occurring, they hypothesize, is "oppositional tolerance," where, over time, the brain pushes back against the antidepressant.

But the authors also note that our lack of scientific understanding of depression leaves room for interpretation.

In his book, "Anatomy of an Epidemic," Whitaker helps us out by noting that, historically, depression had been regarded as a rare illness with a good prognosis. Then antidepressants became the rage. Despite this, too many patients only seemed to be getting worse over the long haul rather than better. According to Whitaker, instead of questioning the med, psychiatry questioned the diagnosis. Overnight, the new consensus was that antidepressants are okay, but the illness is highly prevalent with a poor prognosis.

Thus, ironically, depression became an epidemic.

But what if depression is the wrong name for this epidemic? What if most of what we are observing is not clinical depression at all? And what if not all depressions are the same? These are questions I have been asking on this blog and elsewhere. 

Let's start with the obvious, with the unipolar/bipolar distinction. All too often, people with bipolar walk in the door depressed, are misdiagnosed with unipolar depression, and given an antidepressant. If they are lucky (as I was), the antidepressant will quickly flip them into mania, which will put even the dumbest clinician on notice to change both the diagnosis and treatment.

If the patient is unlucky (as many are), the antidepressant may initially make that individual feel better before feeling worse. Then that individual endures the heartbreak and frustration of being tried on one antidepressant after another, years on end. Ten or 11 years later (the time it usually takes to make an accurate bipolar II diagnosis), a smart clinician finally considers the obvious.

There is now widespread agreement that an antidepressant, even with a concomitant mood stabilizer, does nothing (as a general rule) to improve bipolar. Moreover, we know these meds run a high risk of making it worse.

There is also an emerging consensus that this may be the case for many so-called unipolar depressions, as well. These are individuals that Goodwin and Jamison in their second edition to "Manic-Depressive Illness" characterize as "highly recurrent." In other words, there is a cycling nature to the course of their illness, much like bipolar, even if the "ups" fall well short of mania or hypomania. But give these individuals an antidepressant and that may change. In effect, an antidepressant may turn an unsuspecting unipolar into a bipolar, a point that Whitaker visits in Chapter Nine of his book.

Obviously, psychiatry needs to light a match to the DSM and start over. Whether one calls highly recurrent depression a new form of depression or a new form of bipolar hardly matters, so long as clinicians are put on notice to think twice before prescribing an antidepressant. But that is not the end of the story. Four years ago, I had this to report, from a lecture delivered by Joel Paris of the University of Toronto at the 2006 APA:

In true Axis I depression, Dr Paris explained, when patients come out of a depression, they are nice people again. Individuals with personality disorders, by contrast, can come out of a depression and still have problems with life. Unfortunately, clinicians prefer not to want to hear about personality. It means trouble. They would rather throw more meds at the problem.

Dr Paris was talking about borderline personality disorder, which is often misdiagnosed as a mood disorder. With psychiatry at long last showing signs of breaking off its love affair with Pharma (thanks to psychiatric meds losing their patent protection), personality disorders are starting to get a lot more respect.

Let's take this a step further. Suppose, in some cases, that depression itself could be considered a personality disorder, as some experts are proposing (a rather controversial view) or (much less controversially) as part of one's baseline temperament? (See my January blog post on this.) In this context, depression is a natural (and possibly even healthy) part of a person's personality rather than a deviation from from one's normal healthy state.

To wrap this up for now, imagine a patient walking into a psychiatrist's office manifesting depressive symptoms. Assuming the cause is not physical (such as a thyroid condition) or neurological (such as dementia), we have five (not necessarily mutually exclusive) possibilities, namely:
  1. Classic unipolar depression.
  2. The depressive phase of bipolar disorder, either I or II or cyclothymia.
  3. Something in between, or overlapping with, classic depression and classic bipolar.
  4. A personality disorder, such as borderline.
  5. A personality trait or temperament.
Five possibilities. Four chances to get it wrong. Only one chance to get it right. Is it any wonder that doctors get such bad results or that patients undergo so much misery? But even if the clinician spins the wheel correctly, we are talking numerous sub-possibilities within the one possibility that holds out promise. In other words, even more chances to get it wrong.

Stop this game of antidepressant roulette right now! one wants to cry out.

Next: The game goes on, anyway ...

Previous articles

Are Antidepressants Bad for You?
Are Antidepressants Bad for You? - Part II
Are Antidepressants Bad for You? - Part III

Saturday, November 13, 2010

Rerun: Some Observations on Stigma

From Jan 2009 ...

Today, I completed an email interview with Michael, a patient who has recently set up an excellent website, Stable Moods.

"What more do you think can be done to change the public’s perception of mental illness?" he asked.

That one really got me thinking. "We (patients) have to take more responsibility and stop blaming others," I responded. "We need to recognize that our behavior has put those around us through no end of grief and that they have every right to never want to associate with us."

That was just my warm-up. We tend to think of stigma as something we have to put up with from the general population - and, believe me, there's more than enough of it to go around - but we're not going to get very far doing nothing for ourselves and waiting for others to change.

I've seen far too many patients on the cusp of recovery but going nowhere - stuck - and I can't help thinking a victim mindset has a lot to do with it. Not only do these patients hurt themselves, a lot of them hurt the rest of us. All it takes is just one person to play the bipolar card on someone once too often to turn a would-be sympathizer into a one more reason my life is difficult.

Fortunately, people are capable of forgiving us for our outrageous behavior, but first we need to ask, and second we need to demonstrate good faith.

Meanwhile, we need to make an effort to become role models, to start acting as if we have something to offer the world. An enlightened public is more than willing to embrace us and put up with some of the craziness that goes with the whole package, provided that we set out to become a positive force in their lives.

There has been a major sea change in public attitudes since I was diagnosed 11 years ago. Yes, we are still exposed to a lot of, "He's acting weird, must be bipolar." But we're also hearing more of, "Wow, she's so amazingly smart and creative and personable, must be bipolar."

Next thing, we'll have a bipolar President. Wait, we've already had at least at least three (John Adams, TR, LBJ). More on stigma in a future blog ...

Complete Stable Moods interview

Thursday, November 11, 2010

Rerun: This Veteran's Day

I run this every Veteran's Day and Memorial Day:

This Veterans Day:

Our men and women are returning from two wars. They have witnessed things and felt things that those of us who stayed home have no clue. Their brains have been overwhelmed, their psychic beings shaken to the core.

This Veterans Day:

Our soldiers may leave the battlefield, but they cannot leave their memories there. Very high percentages are returning home with PTSD, depression, and other mental illnesses. Even those without full-blown symptoms have issues to deal with. Others are ticking time bombs. Suicide will claim more of them than enemy gunfire. Many will attempt to cope by turning to alcohol and drugs.

This Veterans Day:

Many brave men and women have no clue what is about to happen to them. They served as heroes, but, like many who served in Vietnam, may wind up homeless. They may be remembered for their bravery, but we will cross the street to avoid them.

This Veterans Day:

It's not just about flags on graves. It's about serving the people who served our country.

This Veterans Day:

Resolve to do something tangible. Advocate. Donate. Get involved with one of the veteran's organizations. Get involved with a mental health group making an outreach to veterans. Do something. Then keep doing it.

This Veterans Day:

It's our turn now.


From Therese Borchard's Beyond Blue:
  • Almost one in three veterans returning from Afghanistan and Iraq confront mental health problems.
  • On an average day in this country, suicide claims another 18 veterans.
  • Approximately 30 percent of veterans treated in the veterans health system suffer from depressive symptoms, two to three times the rate of the general population.
  • More Vietnam veterans have now died from suicide than were killed directly during the war.
  • Approximately 40 percent of homeless veterans have mental illnesses.

Are Antidepressants Bad for You? - Part III

Yesterday, we looked at a review article by Giovanni Fava and Emanuela Offidani that introduced the idea of "oppositional tolerance" in regard to long-term antidepressant use. According to the authors, the few long-term studies we have indicate a three-month limit to antidepressant treatment. Staying on these meds any longer appears to have no impact on avoiding a recurrence. Indeed, in some cases, long-term use may make our depressions worse and set us up for future episodes.

The reason for this, the authors hypothesize, is that as our brains build up a tolerance to these meds, various processes are set in motion that counteract the drug's initial effect which in turn may "propel the illness to a more malignant and treatment-unresponsive course."

The authors note, however, that oppositional tolerance needs to be considered in the broader context of psychiatry's highly suspect diagnostic criteria for mood disorders. This portion of the conversation begins in Robert Whitaker's "Anatomy of an Epidemic":

In Chapter Eight, Whitaker cites community surveys from the 1930s and 40s that found "fewer than one in a thousand adults suffered an episode of clinical depression each year." According to Charlotte Silverman, author of "The Epidemiology of Depression" (1968), and others, depression was primarily an "ailment of middle aged and older persons." Most of the "depressed-only" patients observed by Emil Kraepelin in the early twentieth century experienced just a single episode of depression and only 13 percent had three or more episodes. Even as late as 1972, Guze and Robins of Washington University (St Louis) noted that only one in ten became chronically ill.

Then came the antidepressant era in full force. For some patients, these meds proved to be magic bullets, at least in the early going. But it wasn't long before researchers began reporting on their inordinately high relapse rates (the scientific term is "Prozac poop-out"). According to Whitaker, psychiatry decided this had to do with the course of the illness rather than the effects of the drug. Overnight, psychiatry changed its party line to the effect that depression was everywhere, and that the old epidemiological studies were "flawed." In the words of the American Psychiatric Association, "depression is a highly recurrent and pernicious disorder."

Says Whitaker: "In the short span of forty years depression had been utterly transformed," going from a rare illness with good outcomes to an epidemic that kept visiting havoc its victims.

Giovanni Fava was a lone voice back in 1994 when he dared suggest in an editorial that we need to be paying attention to the man behind the curtain, wondering if meds "may actually worsen, at least in some cases, the progression of the illness which they are supposed to treat." Since Fava was merely posing this as a hypothetical he was easy to dismiss. Whitaker asserts that Fava's concerns "needed to be hushed up," but the APA is not exactly a Star Chamber.

Sixteen years later, Fava is still beating the drum, this time far less tentatively. Fittingly, it is Whitaker in his blog Mad in America who drew attention to Fava's latest contribution. Clearly Whitaker is onto something. In his book, he makes the telling point that if our meds worked as well as Pharma would have us believe, then we wouldn't have illnesses like depression to kick around anymore. Or, at the very least, thanks to treatment, depression would be very rare and relatively benign. This is a point that other commentators have raised as well, including David Healy of Cardiff University.

Instead, in the face of overwhelming evidence that depression has - defiantly, it seems - refused to yield to repeated antidepressant bombardment, psychiatry has changed its tune on the illness. Suddenly, it's everywhere and is highly malignant. Again, Whitaker and Healy and others are in harmony.

Do you see the dots starting to connect? Namely: Problematic meds to treat a vaguely defined illness advanced by those with strong monetary interests, leading to this major fallacy - If it's depression, then one must always treat it with an antidepressant.

But what if it's NOT depression, even if it looks like depression? Or what if not all depressions are the same? And who, precisely, are these people, anyway, these anomalies of psychiatry, who are put on meds that may make them worse rather than better? Why are they being lumped with everyone else?

These are questions that badly need to be asked, that hardly anyone seems to be asking.

Next: We ask the questions ...

Wednesday, November 10, 2010

Are Antidepressants Bad for You? - Part II

Yesterday focused on an important review article by Giovanni Fava of the University of Bologna (Emanuela Offidani, co-author), brought to my attention by Robert Whitaker on his blog, Mad in America. In the review article, Fava and Offidani indicate that long-term use of antidepressant drugs in some cases may actually worsen the outcome of depression. But they also suggest that bad outcomes may have a lot to do with our simplistic notion of depression, which only encourages equally simplistic treatments.

Let's start at the beginning ...

According to Fava and Offidani, antidepressants are much better suited to treating the episode rather than the illness. Thus, if you are feeling depressed, there is a reasonable chance that your antidepressant may boot you out of your current state - for a little while, anyway. The evidence that antidepressants will keep another depression from occurring, however, is far more problematic.

For instance, a 1998 study found that patients on Prozac fared nearly twice as well as those in the placebo group (26 percent relapse vs 48 percent), but only at the 24-week point. After 62 weeks the two groups relapsed about equally. Other studies show relapse rates in the 46 to 65 percent range over one year.

Meanwhile, in some individuals (30 percent in one study, 7 percent in another), depression scores went up among those on an antidepressant rather than down. Also, studies have found that antidepressants appear to increase - not decrease - the frequency of recurrences, and that they increase depression symptoms in those being treated for anxiety.

We know there is a high risk of antidepressants causing bipolar patients to flip into mania or speeding up cycling, but there is also the possibility that these meds may also increase the rate of depressive relapse in this same population.

What is going on?

In their review article, Fava and Offadani devote a lot of attention to the tolerance factor. Thus, in a 1995 study conducted by Fava, patients who relapsed on Prozac at 20 mg responded to Prozac at 40 mg. A related phenomena is "resistance," when a med doesn't work when restarted after it had previously been effective. Percentages from various resistance studies range from 4 to 38 percent. Then there is "discontinuation syndrome," such as headache or sleep disturbance soon after the med is withdrawn. This occurs with far greater frequency in the shorter half-life meds such as Paxil.

The unifying theme, the authors suggest is "oppositional tolerance." In their own words:

According to this model, continued drug treatment may recruit processes that oppose the initial acute effects of a drug or of receptor alterations ... Use of antidepressant drugs may also propel the illness to a more malignant and treatment-unresponsive course ...

We're entering the realm of hypothesis here, but what may be happening, according to the authors, is that the therapeutic modulations that antidepressants induce in the 5HT1A, 5HT1B, and 5HT2 serotonin receptors may, in certain cases, be triggering downstream effects inside the neuron "that are likely to affect the balance of serotonin receptors."

Or a similar result may occur via the HPA axis (the neuroendocrine loop that mediates fight-or-flight). In this scenario, enhanced 5HT1 neurotransmission may activate the HPA axis, which in turn may disturb serotonin receptor function. Stress figures mightily in depression, and while antidepressants may have a protective effect, in some cases there is the possibility of heightened sensitization.

The authors acknowledge there are no studies that prove oppositional tolerance, but the NIMH-underwritten STAR-D trials, they maintain, sheds light on the theory. In STAR-D, 3,600 patients were first tried on Celexa. Of these, 37 percent remitted. Those who didn't recover were tried on other antidepressants or various meds combinations in four successive stages. Sixty-seven percent of those who remained in the study eventually remitted, but owing to relapse the true figure was 43 percent. Thus, the very best that medicine could accomplish was squeeze out a measly 6 percent improvement in the initial recovery rate. Moreover, remission rates decreased after each treatment while relapse rates increased.

STAR-D most convincingly demonstrated that when the first or second antidepressant fails, there is little prospect of the third or fourth one proving to be the magic bullet. But was this due to a predisposition on the part of the individual patient or to the cumulative effects of repeated antidepressant administration? Fava and Offadani raise the possibility of the latter, saying that switching or augmenting meds "may propel depressive illness into a refractory phase, characterized by low remission, high relapse and high intolerance."

This sets up their conclusion:

When we prolong treatment over 6–9months we may recruit processes that oppose the initial acute effects of antidepressant drugs (loss of clinical effects). We may also propel the illness to a malignant and treatment-unresponsive course that may take the form of resistance or episode acceleration. When drug treatment ends, these processes may be unopposed and yield withdrawal symptoms and increased vulnerability to relapse. Such processes are not necessarily reversible. The more we switch or potentiate antidepressant drugs the more likely is oppositional tolerance to take place.

But they also pull their punch with this final sentence: 

The phenomena we have described, however, are difficult to interpret unless a precise diagnostic categorization of mood disturbances is made, taking into consideration both their longitudinal course, the unipolar/bipolar distinction and their subtypes.

Here, of course, is where the real discussion begins.

Next: The real discussion begins ...

Tuesday, November 9, 2010

Are Antidepressants Bad for You?

This is the eleventh in my series based on talking points raised by Robert Whitaker's eye-opening "Anatomy of an Epidemic."

We take a slight detour. A late Oct blog entry to Robert Whitaker's "Mad in America" contained this intriguing title: Do Antidepressants Worsen the Long-term Course of Depression? ...

The piece extracted some of the main points from a review article by Giovanni Fava of the University of Bologna. Here is Whitaker's summation:
  • After six months of antidepressant treatment, the drugs "generally fail to protect" against a return of depressive symptoms. (In other words, maintenance treatment is ineffective, compared to placebo.)
  • Two-thirds of patients maintained on antidepressants suffer from "residual symptoms," with "anxiety, insomnia, fatigue, cognitive impairment, and irritability the most commonly reported."
  • As patients are switched from one antidepressant to another or to a polypharmacy regimen, their illness may be propelled "into a refractory phase, characterized by low remission, high relapse and high intolerance."
  • Antidepressants increase the risk of a "switch" into mania, and thus into bipolar illness. Antidepressants also increase the risk that bipolar patients will become rapid cyclers, and that bipolar patients will develop a syndrome dubbed "Chronic Irritable Dysphoria."
Make no mistake, right from the get-go Fava very unambiguously sounds the alarm:

It was suggested that long-term use of antidepressant drugs may increase, in some cases, the biochemical vulnerability to depression and worsen its long-term outcome and symptomatic expression, decreasing both its likelihood of subsequent response to pharmacological treatment and the duration of symptom-free periods.

In summing up, he notes:

When we prolong treatment over 6–9months we may recruit processes that oppose the initial acute effects of antidepressant drugs (loss of clinical effects). We may also propel the illness to a malignant and treatment-unresponsive course that may take the form of resistance or episode acceleration. When drug treatment ends, these processes may be unopposed and yield withdrawal symptoms and increased vulnerability to relapse. Such processes are not necessarily reversible. The more we switch or potentiate antidepressant drugs the more likely is oppositional tolerance to take place.

But there is this important qualifier:

The phenomena we have described, however, are difficult to interpret unless a precise diagnostic categorization of mood disturbances is made, taking into consideration both their longitudinal course, the unipolar/bipolar distinction and their subtypes.

Dang! Nuances again.

Next: A look at the nuances ...

Monday, November 8, 2010

Food for Thought

For the great enemy of truth is very often not the lie — deliberate, contrived, and dishonest — but the myth — persistent, persuasive, and unrealistic. Too often we hold fast to the cliches of our forebears. We subject all facts to a prefabricated set of interpretations. We enjoy the comfort of opinion without the discomfort of thought.

- JFK, commencement address, Yale University,  June 11, 1962, written by Ted Sorensen, JFK's counselor and speechwriter, who died last week, age 82.

Saturday, November 6, 2010

Ruminations on Madness

A brief timeout from my usual blogging for this announcement. Check out the new addition to my blog roll. In the course of researching the issues raised by Robert Whitaker's "Anatomy of an Epidemic," I came across Ruminations on Madness, by "N." N is a PhD candidate who identifies herself as having schizophrenia. Why not just say "PhD candidate who has schizophrenia"? Apparently, things are not so simple. In one post, she brings up a set of "binaries," one of them being: "If a person is working on a PhD, then that person cannot possibly have schizophrenia or that it is somehow not serious" vs "If a person has schizophrenia then that person should not be working on a PhD."

Interesting. A lot of crazy stuff gets said about bipolars (that's me), but this isn't one of them.

N shares many of the same reservations I have about Whitaker, namely that he raises important issues but that he is prone to misrepresenting scientific studies to make a point. She would have been entirely justified in discrediting Whitaker entirely, but instead simply holds him accountable. How refreshing.

N applies her same highly nuanced sensibility to breaking down a whole range of complex issues - scientific, social, philosophical. In addition, she has just started a spin-off blog, Schizophrenia Research.

Quality bloggers have a tendency to burn out before their blog acquires the necessary traction, and I would hate to see this happen to N. You might want to pay her a visit and drop an encouraging note. 

Friday, November 5, 2010

Supersensitivity Psychosis: The Evidence

This is the tenth in my series based on talking points raised by Robert Whitaker's eye-opening "Anatomy of an Epidemic."

We left off with the shocking proposition that our antipsychotics may actually make us more prone rather than less prone to psychosis, thus turning good prognosis patients into chronic bad prognosis ones. The idea was first advanced in 1978 by Guy Chouinard and Barry Jones of McGill University, who coined the term, "supersensitivity psychosis."

We see supersensitivity at work in tardive dyskinesia, when one dopamine pathway (nigrostriatal) is overstimulated after post-synaptic neurons habituate to prolonged antipsychotic exposure. Since we're pretty sure this is true, Chouinard and Jones deduced that it was likely that another dopamine pathway (mesolimbic) was getting overwhelmed, as well. And, of all the crazy things, the particular side effect coming out of this pathway would be psychosis.

That's right - a med administered to treat psychosis with a side effect of psychosis.

This is not as crazy as it sounds. Patients of all categories experience "rebound" symptoms across all classes of meds when they are abruptly withdrawn after long term administration or when doses are lowered too quickly. Usually, the result is temporary, but even a remote prospect of this happening is extremely unsettling. Whitaker states that we may be better off by just saying no to antipsychotics over the long haul, where the best evidence we have indicates that patients fare better by not refilling their prescriptions.

Chouinard and Jones don't go nearly this far, instead restricting their focus to treating supersensitivity psychosis as it occurs and to picking up its early warning signs.

In their 1978 article, Chouinard and Jones referred to a study they conducted on 32 patients. Half the patients were taken off their antipsychotic and given a placebo. The eight patients whose condition deteriorated into psychosis also experienced tardive dyskinesia, lending credence to the  proposition that the two effects were related, induced by the same phenomenon over different pathways.

But here's the catch: How can you tell supersensitivity psychosis from the real thing? After all, if you take a patient off their antipsychotic, it stands to reason the illness will reassert itself. With tardive dyskinesia we know the effect is from the drug rather than the natural course of the illness. But what about psychosis? Chouinard tackled this problem in a 1990 article by proposing diagnostic criteria for "neuroleptic-induced supersensitivity psychosis." His main distinguishing feature was that once the antipsychotic is withdrawn or the dose lowered the psychosis comes on quicker and with greater frequency than illness-related psychosis.

Whitaker doesn't bring this up in his book. Indeed, his whole argument rests on the proposition that you can't tell the two apart, or at least that researchers have not taken the trouble. This is why relapse-prevention studies (which involve taking responding patients off the trial drug) are bogus, according to Whitaker, as the returning psychosis cannot be unequivocally attributed to the illness. As he describes it: "The severe relapse suffered by many patients withdrawn from antipsychotics was not necessarily the result of the 'disease' returning, but rather was drug-related."

Wait. We don't know for sure if it was drug-related. Whitaker has no business saying that. But he does have a point. At the very least, the possibility of supersensitivity psychosis raises "reasonable doubt" in all long-term antipsychotics trials, rendering them null and void.

But the same reasonable doubt exists with Chouinard's studies, as well, meaning that we don't really know the incidence of supersensitivity psychosis (Chouinard claims it may be as high as 43 percent). According to Joanna Moncrieff of University College London in a 2006 review article, "there is the problem of distinguishing the natural history of the underlying disorder from effects related to drug withdrawal," a point that Chouinard acknowledges in a 2008 piece.

Further research would shed light on the situation, but this raises major ethical issues, Moncrieff points out, as "it is difficult to justify experimental studies involving rapid discontinuation of drugs." Whitaker would have no choice but to agree. In the foreword to his book, he mentions clinical trials that came to his attention "that involved withdrawing schizophrenia patients from their antipsychotic medications, which was the unethical thing to do."

So where do we stand? Obviously there is something to the supersensitivity psychosis hypothesis. It may be as serious as Whitaker makes it out to be, but the hard evidence is lacking, and will be for some time to come. It may be as prevalent as Chouinard indicates, but again the hard evidence is lacking. Moreover, Chouinard is quick to add that most of this is reversible, upon the resumption of the antipsychotic. It is worth noting that Chouinard limits his focus to spotting and treating supersensitivity psychosis (often with higher doses and a concomitant mood stabilizer). The wisdom or folly of remaining on an antipsychotic is Whitaker's line of inquiry, not Chouinard's.

Does this mean that Whitaker is off-base? Hardly. His thesis may run far ahead of the evidence, but is nonetheless perfectly in line with the speculative dots he is connecting. We know that antipsychotics are blunt instruments at best. We know that many, if not most, patients on antipsychotics continue to lead miserable lives. Likewise, we know that quite a few patients may be better off not taking antipsychotics. Finally, we know that there is a lot we do not know.

We are already aware that there are many reasons to think twice before taking an antipsychotic, much less remaining on one. Whitaker has given us a few more reasons to be concerned. He may not be right, but someone needs to prove him wrong.

Wednesday, November 3, 2010

Supersensitivity Psychosis: Is There Such a Thing, and If There Is Then Why the Hell Haven't We Heard About It Before?

This is the ninth in my series based on talking points raised by Robert Whitaker's eye-opening "Anatomy of an Epidemic."

In his book, "Anatomy of an Epidemic," Robert Whitaker easily debunked the chemical imbalance myth (see earlier blog piece), which rested on nothing more than some observations in search of an explanation.

The observation: "Certain drugs reduce psychiatric symptoms."

The explanation: "It must be because they correct a chemical imbalance."

The reality: "The brain is not chemical soup."

Whitaker then went on to cite with approval a different set of observations in search of an explanation called "supersensitivity psychosis." Supersensitivity psychosis is central to the whole point of Whitaker's book, which posits that our meds may actually worsen rather than improve the natural course of our illness.

This goes much further than stating that well-known side effects tend to make us feel worse rather than better. Suppose, instead, Whitaker asks, our meds actually amplify the very symptoms they are supposed to remedy? We know, for instance, that indiscriminate use of antidepressants can turn depressives into bipolars and classic bipolars into rapid-cycling bipolars.

What about antipsychotics? Are they really as "anti" as psychiatry makes them out to be, or is there a bit of "pro" to their effect? After all, if these meds truly worked the way Pharma would have us believe, there would be a lot less incidence of mental illness, with a lot less severity, rather than a lot more. Consider this the observation. The explanation may have something to do with many of us being hypersensitive to our meds. But does reality bear this out?

The story begins with the investigations of Guy Chouinard and Barry Jones of McGill University back in the late seventies. We know that antipsychotics knock out psychosis by blocking post-synaptic dopamine D2 receptors. But the brain compensates by, amongst other things, increasing the receptor binding sites on these very same neurons. This has been shown in postmortem brain samples of rats, and more recently in brain scans of humans.

If the antipsychotic (or neuroleptic) is suddenly withdrawn, the brain takes time to readjust, during which all manner of bad things may happen. Down in the nigrostriatal dopamine pathway, neurons are firing too rapidly to maintain full motor control, resulting in facial tics, agitation, and other disturbances. Or, should the patient stay on the med, the morphed neurons may reach a point of no-return. These disturbances may in time manifest as tardive dyskinesia, which is permanent.

So far, so good. But what if, Chouinard and Jones asked, something similar went on in the very dopamine pathway - the mesolimbic pathway - that antipsychotics are supposed to restore to normal? If you suddenly withdrew the antipsychotic, could "rebound" psychosis occur? And could a permanently altered brain turn good prognosis patients into chronic bad prognosis ones? As the authors explained in a 1980 article:

According to this hypothesis, the cessation of maintenance neuroleptic medication induces a relative increase in the mesolimbic dopamine function, leading to psychotic relapse or deterioration in the same manner as tardive dyskinesia can emerge or worsen when medication is stopped or decreased.

In a 1990 paper, Chouinard estimated the likelihood of 43 percent of patients on neuroleptics being affected in this manner. In one of his case studies, he cited "Mrs B," who had five relapses of acute psychosis over the first 22 years of her illness vs six in the last 10, and was no longer responding to increased doses.

"What was psychiatry supposed to do with this information?" asks Whitaker in his book. "It clearly imperiled the field's very foundation." Whitaker then relates how the dean of receptorology, Solomon Snyder of Johns Hopkins, came to psychiatry's rescue by assuring readers in a 1986 book that talk of supersensitivity psychosis was premature. Soon after, the hypothesis was consigned to the "interesting" file and the field breathed a sigh of relief.

Today, Whitaker observes, "the notion that antipsychotics increase the likelihood that a person diagnosed with schizophrenia will become chronically ill seems, on the face of it, absurd." Ask anyone - the top experts, the man on the street - and they "will attest that antipsychotics are essential for treating schizophrenia."

So is psychiatry to be damned for turning its back on us, or is Whitaker reaching too far in his quest for an explanation? Or are there simply a lot more nuances to the issue than he suggests?

Next: We look at the nuances ...   

Previous blog pieces:

Tuning Out the Distractions

Thanks to Stupid Advocacy, Your Life is Worth Just One Penny

The Study Psychiatry Wishes Would Just Go Away - Part II

The Study Psychiatry Wishes Would Just Go Away

Is the Cure Worse Than The Illness?

The Whitaker Controversy: An Irony in Search of Nuance

If Meds Work as Well as Our Psychiatrists Tell Us, Why Do We Have MORE Mental Illness Today Rather Than Less?

RIP: Chemical Imbalance in the Brain

Tuesday, November 2, 2010

Rerun - Thinking Outside the Box: Lessons in Military History, Part II

I'm doing some research based on some talking points Robert Whitaker raised in his book, "Anatomy of an Epidemic" and a recent blog piece of his. In the meantime, another history lesson, published in July last year ...

In Part I, we looked at how thinking outside the box enabled the Romans to defeat rival Carthage at its own game in the First Punic War. Instead of facing the vastly more experienced Carthaginian navy on their own terms, the newbie Romans figured out, in essence, how to stage a land battle at sea.

In Part II, we investigate a mirror opposite, how the American Revolution’s best general (on both sides) took on the British Royal Navy deep in the American wilderness.

The Battle of Valcour Island, 1776

Washington forced the British garrison out of Boston in the spring of 1776, but they returned with a vengeance several months later, with a huge fleet bearing a large army weighing anchor in New York and another armada sailing up the St Lawrence into Quebec.

The British had no problem routing Washington’s army just outside New York City and reducing it to a remnant as it occupied the city and asserted itself in New Jersey. In Canada, they easily swept aside the badly outnumbered Americans there. A British invasion from the north and into New York would bring a swift end to the ill-fated colonial rebellion.

One of the American commanders in Canada, Benedict Arnold, fought a brilliant delaying action, destroying British ships, fortifications, and sawmills as he retreated south.

The British Army followed to the northern shore of Lake Champlain, deep in what was then impenetrable wilderness, while the Americans regrouped on the southern end. This set the stage for one of the strangest campaigns in military history.

The key to transporting the British Army south to New York City was via the waterways, first Lake Champlain, then Lake George, then down the Hudson. But first the British needed to build a fleet, and so did the Americans, if they intended to stop the British.

The Americans had already commandeered a sloop or two, but were at a decided disadvantage, lacking the necessary shipwrights and sailors, as well as supplies and resources.

The British, in the meantime, came well prepared, with 10 prefabricated ships, plus a 180-ton warship that they took apart in Canada, carted overland, and reassembled on Lake Champlain, not to mention the necessary shipwrights to build more boats. By the end of the summer, the British had a fleet of 25 heavily-armed vessels, commanded by a captain of the Royal Navy, together with a full complement of officers and sailors.

More boats were equipped to transport 9,000 British Army regulars.

The Americans, under the leadership of Benedict Arnold, proved extremely resourceful in knocking out their own boats - some little more than wooden platforms - to bring their roster to 15. These were built by mostly carpenter labor, manned in large part by ragged soldiers turned sailors. Arnold was a general who happened to have experience as captain of his own merchant ship.

In mid-October, as the nearby mountains turned white with snow, Arnold headed north with his strange flotilla of 500 “sailors” to meet the British. His intention was to lure the British into the narrow rocky strip of water between Valcour Island and the western shore of Lake Champlain. Here, the British would have difficulty bringing their superior firepower and sailing skills to bear.

The disadvantage was the Americans were backed into a corner, with nowhere to run.

The inferior American fleet held up under a withering British bombardment at extremely close range, managing to inflict serious damage in the process, but as the sun set it was clear the day belonged to the British. Virtually every American boat was ready for salvage. The British, meanwhile, were sitting pretty with ships that had not yet joined battle.

Facing the certainty of total annihilation, Arnold effected a brilliant escape in the dead of night, but with the British in hot pursuit. Under hellish weather conditions, one ship was captured while others had to be scuttled. The remnants of his fleet managed to make it to a refuge, where the boats were torched.

Arnold succeeded in leading the 200 remaining men under his command overland to an American fortification at Crown Point, thence (with the Crown Point garrison) to Ticonderoga, where a large contingent of American irregulars were dug in.

After that, the only thing standing between the British advance down the Hudson (and inevitable victory) was the oncoming winter. It turned out in losing the battle, Arnold had in fact set the scene for winning the war. By forcing the enemy to engage in an arms race way out in the middle of nowhere and then join battle, Arnold had run out the clock, delaying the British offensive by a good three months.

The Brits' only option was to retire to winter quarters in Quebec and try again next spring. This bought the American cause a precious year, time for Washington to rebuild his ragtag remnant of an army into a highly-trained fighting force. Time to assemble a strong regular army on the northern front.

When the British attempted a second invasion a year later, the Americans were ready, with an overwhelming force at Saratoga. The outstanding commander in the field was Benedict Arnold.

Arnold’s extraordinary military achievement is a shining example of thinking outside the box, of reframing issues and coming up with solutions where none seemingly exist. Unfortunately, by shifting his allegiance to the British later in the war and thus betraying his country, Arnold is much better known as a sober object lesson in thinking far too far outside the box.