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 ... 

Rebutting Whitaker: Not Such a Good Idea - Part II

On Saturday, I published a piece that said it is not such a good idea to claim to rebut (or for that matter refute or repudiate) Robert Whitaker and his 2010 book, “Anatomy of an Epidemic.” Not unless Whitaker happens to be a flat-earther making up his own facts.

The danger with framing a counter-argument in the form of a rebuttal is that you have to declare in advance that you are about to score a first-round knock-out. So, even if you win on points in 15 rounds you have lost. Earlier this year, Andrew Nierenberg of Harvard went for the knock-out, and disgraced himself and psychiatry in the process.  (See Part I and Part II to "Whitaker vs Quack Psychiatry.")

Rebuttals are hardly an impossibility, but you need to bring both your A-game and a measure of respect for the other side and all interested parties. For a stellar example, go to YouTube and view Robert Lustig’s masterful demolition of conventional and scientific wisdom concerning weight gain and obesity.

The most recent rebuttal claim on Whitaker came in the form of a confused two-part commentary by William Glazer MD on Behavioral Healthcare. In my previous piece, I showed how Dr Glazer most unambiguously failed in his claims that Whitaker’s thesis was “sensational” and “scientifically unsound.”

Would Dr Glazer have been more successful had he merely set out to knock holes in Whitaker’s arguments? Let’s examine the hole-knocking:

Whitaker advanced the novel proposition that psychiatric meds have caused an increase (rather than an expected decrease) in mental illness. Exhibit A in Glazer’s counter-argument were two authoritative population studies done ten years apart. The early 2000s data was virtually the same as the early 1990s data.

But Whitaker went a lot further back in his comparisons, digging into research from the sixties and earlier. Glazer’s comparing modern data to modern data was the equivalent of a cheap accounting stunt. This is where Glazer really sets his foot in it. In citing the mental illness prevalence data at 29 percent and 30 percent from both studies, Dr Glazer makes this extraordinary statement:

These figures hardly support the notion of an “epidemic” of mental illness, the assertion on which Whitaker rests his case, as well as the provocative title of his book.

No mental illness epidemic, Dr Glazer? Really? Let’s examine the threshold levels for what constitutes an epidemic. In 2003, the US Surgeon General declared: “We have an epidemic of childhood obesity.” How many kids were obese? Fifteen percent (triple the rate of forty years earlier).

Glazer is on far more solid ground when he takes issue with other population and disability figures Whitaker cites in his book, but this was already covered by Daniel Carlat in his two blog pieces earlier this year. (See my reviews: A Discussion at Last, and When Is Speculation Justified?) I, too, have expressed my concerns with Whitaker over this, but these hardly rate as rebuttals. Quibble all we want, we are still looking at an alarming 30 percent prevalence rate of mental illness, an epidemic.

Now we get to the meat of Whitaker’s arguments, namely: 1) Prolonged antipsychotic use may result in a form of “rebound psychosis”; 2) In many cases, schizophrenia patients may do better not on meds; 3) Prolonged antidepressant use may set up “oppositional tolerance” that worsens the course of depression.

In numerous blog pieces, I cited Whitaker with moving violations for playing fast and loose with the evidence. In short, the studies Whitaker cites do not actually prove his claims. But they do support his claims. The scientific conversation is full of this type of discourse. Thus, support that is short of proof carries a certain level of scientific validity. So - can Glazer knock out the supports? Or will he choose instead to recycle Nierenberg personal insults? You guessed it:

“Mr. Whitaker needs a basic course on principles of epidemiologic research, specifically on the concept of ‘susceptibility bias.’”

This is the same Dr Nierenberg who in debating Whitaker miscited a longitudinal study as “restrospective.” Um - who needs the basic course?

Speaking of longitudinal studies, Glazer also repeats Nierenberg’s mischaracterization of an NIMH study as a 20-year study supporting the long-term effects of antidepressants. If there were such a study, then we might have some strong counter-evidence to the “oppositional tolerance" hypothesis that Whitaker advances. Yes, there was an NIMH study, but it merely investigated long-term illness outcomes, not long-term antidepressant use. The study does not say that patients were on antidepressants for 20 years, nor does it purport to make a finding based on long-term use.

Zen koan: If psychiatrists quote howling mistatements from fellow psychiatrists enough times, do the howling misstatements eventually become scientific fact?

Yes, apparently. In the words of Dr Glazer:

The knowledge base for psychiatric medications is evolving, but it has not come anywhere near the point where conclusions can be reached about whether they cause disability. Such a conclusion should rest in the hands of scientists, not reporters.

I could go on and on, rebutting Dr Glazer's rebuttals, but I have better things to do. Instead, I will leave the last word to someone who actually knows what she is talking about. Corinna West is actively involved in the recovery movement. In a blog piece entitled, It Feels So Great To Be Off Meds, she writes: 

I’m not anti-medication, but I am anti-bullshit. I know that medications truly help some people, and some people do well on them. Those people should feel free to continue using them. However, I think all people should be given honest information about psychiatric meds before being put on them. We should be told how hard they can be to get off, and that there is not a ton of research showing long term effectiveness for medications. We should be given the truth that the chemical imbalance theory has not proven to be true. We should be given help and support for getting back off the medications as soon as possible. This would be the best way to help the 40% of people that do not respond to any given medication and might actually be harmed by it. In our current system, people unhelped by medications are only given more medications as well as the message that they are doing something wrong if they’re not recovering.

Rebutting Whitaker: Not Such a Good Idea

In Oct last year, I began a series of pieces based on Robert Whitaker’s shot heard ‘round the world, his 2010 book “Anatomy of an Epidemic.” Whitaker’s astonishing thesis is that psychiatric meds have been a contributing factor to the apparent global rise in mental illness.

Yes, we know our meds may make us worse rather than better, but this comes up in the context of side effects or trade-offs (such as weight gain and cognitive impairments). Whitaker goes a step farther in claiming that many of our meds actually worsen the very conditions they were meant to alleviate, namely:

• Long-term antipsychotic use may bring on psychosis.
• Long-term antidepressant use may bring on depression and affective instability.
• Any kind of antidepressant use may turn those who never experienced mania in their lives into life-long bipolars.

In my initial series of blog pieces and numerous follow-ups, I took serious issue with Mr Whitaker’s fast and loose interpretation of the scientific evidence he cites in his book, not to mention his mindlessly unqualified endorsements of the antipsychiatry movement and his ill-informed cheap shots against advocacy groups that actually get off their asses and help people, such as NAMI (disclosure: I serve on the board of NAMI San Diego).

But I also concluded that Mr Whitaker had made the equivalent of a “case to answer,” a strong prosecutorial argument that demands an equally strong counter-argument from the other side. In other words, until psychiatry can present a convincing case of its own - on point, with strong scientific evidence - any fair-minded jury would have to decide in favor of Whitaker.

So, for right now, in the absence to date of any credible marshaling of the facts from psychiatry, Whitaker stands as the most authoritative voice on psychiatric treatment. A very sad state of affairs.

Yes, Daniel Carlat in two blog pieces (see my reviews: A Discussion at Last, and When Is Speculation Justified?) raised some thoughtful concerns, but he came across more like a woman (and in rare cases a man) on a first date wondering how to dress for the occasion. Andrew Nierenberg, one of psychiatry’s leading authorities on mood disorders, in a grand rounds debate, purported to “refute” and “repudiate” Whitaker, only to embarrass himself and his profession in a DSM-worthy display of disordered thinking and outrageous conduct. (See Part I and Part II to "Whitaker vs Quack Psychiatry.")

The latest criticism of Whitaker is in the form of a two-part piece (Part I and Part II) on "Behavioral Healthcare" by William Glazer MD. Dr Glazer runs his own consultancy, and has been affiliated with Yale and Harvard. Dr Glazer is a welcome voice to the conversation, but from the very beginning he sets up his counter-argument to fail.

“Rebuttal: Questioning the validity of ‘Anatomy of an Epidemic'”, reads the title to his first piece. “Whitaker's claims are ‘sensational’ but scientifically unsound,” reads the subheading.

So, to meet his own criteria in making his case, Dr Glazer would have to prove the falsity of Whitaker’s argument. Not only that, he would have to demonstrate that there is no scientific basis to Whitaker. The catch is that Whitaker is no mere flat-earther engaging in pseudo-science. His conclusions - as far-fetched as they may appear to someone considering the issue for the first time - are strongly grounded in findings published in mainstream journals, not to mention the observations of some of the leading experts in the field.

In addition, to shoot down Whitaker, Dr Glazer would have to marshal his own scientific evidence. This would involve citing studies that convincingly demonstrate the long-term efficacy and safety of numerous classes of psychiatric meds. You would think this would be a very easy mission to accomplish, but these studies simply do not exist. Here, for instance, is a key disclosure from the Depakote product labeling:

The effectiveness of valproate for long-term use in mania, i.e. for more than 3 weeks, has not been demonstrated in controlled clinical trials.

An older version of the labeling read:

The effectiveness of Depakote ER for long-term use in mania, i.e. for more than 3 weeks, has not been systematically evaluated in controlled clinical trials.

So here is the situation: We know it is common psychiatric practice to prescribe Depakote for long-term use in stable patients to prevent relapse or recurrence into mania. Yet the drug has only been successfully tested on a floridly manic group of patients for three weeks.

This is hardly an isolated example. Time and time again, in picking through the long-term data, (with the possible exception of lithium) all we come up with are the equivalent of 18-minute gaps in the tape.

Are we to conclude, then, that psychiatry is “scientifically unsound?” Yes, indeed, if we are to apply Dr Glazer’s extremely reckless terminology. I trust you get the point: The truth is certainly out there, but the facts are extremely hard to come by. The best we can do is make intelligent guesses based on the very limited information available to us.

In a sense, psychiatric treatment equates to meteorological forecasting - impressive in the short-term but highly problematic over the long-haul.  

So forget about rebutting Whitaker. Psychiatry is in no position to do that. The best it can do is interpret the same data in a way that helps all of us make informed decisions. I’m still waiting.

More to come ...

Hats Off to Whitaker

Just a quick note that last week Robert Whitaker received the prestigious Investigative Reporters and Editors Award for his book, "Anatomy of an Epidemic." As regular readers of this blog are well aware, I have published at least 10 commentaries here based on his book, plus several more that used his book as a starting point for other topics. Some of my commentary was highly critical of Whitaker, but always in the context of acknowledging him as a welcome and vital voice and a breath of fresh air.

In singling out Whitaker, the IRE notes:

This eye-opening investigation of the pharmaceutical industry and its relationship with the medical system lays out troubling evidence that the very medications prescribed for mental illness may, in increasing measure, be part of the problem. Whitaker marshals evidence to suggest medications “increase the risk that a person will become disabled” permanently by disorders such as depression, bipolar illness and schizophrenia. This book provides an in-depth exploration of medical studies and science and intersperses compelling anecdotal examples. In the end, Whitaker punches holes in the conventional wisdom of treatment of mental illness with drugs.

Took the words right out of my mouth. Please-please-please, read his book. Warm congrats, Robert, from a sometimes critic but a very ardent supporter.  

Carlat's Response to Whitaker - When is Speculation Justified?

We left off with a psychiatrist, via his blog, actually engaging Robert Whitaker, author of “Anatomy of an Epidemic,” in a discussion. In the first of two blog posts, Daniel Carlat, producer of The Carlat Report and author of “Unhinged,” acknowledged that Whitaker had “his basic facts right,” but disagreed “with his interpretation of the facts.”

This was a refreshing contrast to Andrew Nierenberg’s Psychiatrists Gone Wild performance in reaction to Whitaker’s recent grand rounds at Mass General.

Whitaker’s central thesis is that the reason psychiatric disabilities are much higher today is because of widespread meds use rather than despite widespread meds use. Dr Carlat says there are more plausible explanations for the higher disabilities rate, namely people today are more likely to pick up both a diagnosis and a disability simply by passing Go.

This lack of constancy, contends Dr Carlat in his second post, applies to the diagnosis of schizophrenia, as well, which back in the old days seemed to have been used as a catch-all for all manner of unusual behavior. The pre-DSM-III (1980) studies Whitaker largely relies on, says Dr Carlat, would have included a lot of patients who did not have true schizophrenia and thus would have done just fine without a schizophrenia med.

Dr Carlat has a point, but if you were to exclude the studies Whitaker cites based solely on this criteria, then you need to exclude EVERY schizophrenia study from this era, including authoritative gene studies that showed schizophrenia is clustered in families and is inherited from generation to generation, as well as all the evidence in support of Thorazine’s efficacy.

But for the sake of argument, let’s throw out two ancient long-term WHO studies that Whitaker heavily relied on showing that schizophrenia patients in developing countries (where psychiatric meds are in short supply) had a far better course and outcome than patients in developed countries. Let’s substitute, instead, a 2004 WHO study that employed DSM-IV criteria to measure 12-month prevalence rates of various serious mental disorders (not including schizophrenia) in 14 countries. That survey found, amongst other things, that Nigeria had the lowest rate of mood disorders (0.8 percent) while the US had the highest (9.6 percent).

Not exactly on point, but definitely on pattern. Something strange is clearly going on.

There is one modern study almost entirely on point, which Whitaker employs as his trump card. This is the now famous 2007 “Harrow study” conducted by Martin Harrow of the University of Illinois, which indicated that schizophrenia patients not on meds fared way better over 15 years than those on meds. The catch is the study measured for something quite a bit different, which Whitaker fails to mention in his book.

Dr Carlat stated the obvious, namely that “observational” studies of this type are not likely to yield definitive conclusions. Moreover, it stands to reason that the ones who do well off their meds are likely to be a different breed of patient.

Indeed, it was precisely this issue that Dr Harrow concerned himself with. The true finding in his study was that a certain subgroup of “good prognosis” patients (such as ones with a prior work history) fared better over the long haul off meds than on meds, suggesting that "not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives."

In an earlier piece, I issued Whitaker a moving violation for reporting this study as if it were a clinical trial testing for the efficacy of antipsychotic medications.

But then comes a point where criticism becomes quibbling. Dr Nierenberg egregiously crossed that line when he went postal on Whitaker. Dr Carlat is in the safe zone, but did he miss the big picture? Basically, if someone is shouting Fire! through a cell phone, you investigate whether there is a fire. You don’t get into a discussion about whether the caller ran over his alloted cell phone minutes.

Pulling data from an earlier study to reach a different type of finding goes on all the time in academia. It’s called a “secondary analysis” and when it’s done right it vastly increases the value of the original data. Basically, Whitaker performed his own secondary analysis.

So then the question becomes one of whether Harrrow’s data justifies Whitaker’s conclusions. The answer is yes - to a point. Clearly the patients who fared best in Harrow’s study were the ones off their meds. Whitaker is on very safe ground here. But then he presses his luck by concluding that it was the antipsychotic medications that worsened the outcomes of the ones on their meds. Here, he has stepped into the quicksand of speculation, and Dr Carlat correctly takes him to task.

In his blog, Whitaker defends himself against earlier similar charges by arguing that the Harrow data applies across all the subgroups of patients in his study. But in a 64-patient study parsed into numerous subgroups, we're taking of differences measured in low single figures. (Thanks to Ruminations on Madness for this observation).

So do we dismiss Whitaker’s speculations as out-of-hand? Absolutely not. The DSM-IV - psychiatry’s diagnostic bible - is basically speculation bound between two covers. Every prescription for a psychiatric med that a doctor writes is a speculation approved by the FDA.

We must never forget the big picture: If our meds worked the way Pharma claims and psychiatry believes, we wouldn’t have mental illness to kick around anymore. Instead, we have an epidemic. So what the hell is going on? Someone has to start speculating. Dr Carlat, to his credit, seems to have acknowledged this in the conclusion to his second post:

Over the last few days, I've spent many hours thinking and writing about Anatomy of an Epidemic. Mostly, I've chipped away at its central thesis, and yet the fact that this powerful book has riveted my attention for so long means something. It's fascinating. It's enthralling. And it is the work of a highly intelligent and inquiring mind - a person who is struggling to understand the nature of psychiatric treatment.  Put it on your reading list, and join the debate.

Carlat's Response to Whitaker - A Discussion at Last

We left off with a self-proclaimed “refutation” and “repudiation” by Andrew Nierenberg of Harvard that neither refuted nor repudiated “Anatomy of an Epidemic” by Robert Whitaker. In a response to a grand rounds delivered by Whitaker at Mass Gen on Jan 13, Dr Nierenberg accused Whitaker of “misinformation, simplistic interpretations of statistics, faulty reasoning, and wrong conclusions,” but when the dust cleared the perpetrator of these crimes turned out to be Dr Nierenberg himself.

Throw in his gratuitous personal attacks on Whitaker and we have clear evidence of a psychiatrist gone wild. Of all things, Whitaker came out totally unscathed.

I’m sure we can fashion an ancient Chinese proverb from Dr Nierenberg’s oppositionally defiant behavior, but the clear lesson is that virtually all refutations are doomed to fail (even against such palpably absurd beliefs as “creation science”). Refuting the refuter, needless to say, is like shooting fish in a barrel.

So would a more reasoned approach, say one that actually acknowledged the validity of Whitaker’s arguments, have been far more effective? Funny you should ask.

Daniel Carlat produces The Carlat Report and is the author of “Unhinged,” which is highly critical of Pharma marketing dressed up as science. In late Jan, in the first of a two-part review on his blog, Carlat noted:

My overall take is that Whitaker has his basic facts right, and that he communicates them in a compelling style that I envy. But I disagree with his interpretation of the facts.

Now we’re getting somewhere.

Dr Carlat restates Whitaker’s thesis that the steep rise in psychiatric disabilities over recent years has coincided with a similar rise in psychiatric meds prescriptions. Yes, this is true, Dr Carlat agrees, but “correlation does not imply causation.” To say that med use has actually caused the disability, as Whitaker claims, is a stretch. There are other factors involved, Dr Carlat says, including:

There are more psychiatric disorders to diagnose - 297 in the current DSM, about the same as the DSM-III-R from 1987 (at 292), a bit more than the DSM-III of 1980 (at 265), a lot more than the DSM-II of 1968 (at 182), and a whole lot more than the DSM-I of 1952 (at 106). Dr Carlat contends that “the rise in diagnosis has been largely driven by changes in disease classification and subsequent training - not by toxic medications.”

Dr Carlat also notes that because there are more treatments available, doctors have more of an incentive to make a diagnosis. In other words, doctors are not inclined to make a diagnosis for something they cannot treat.

Then Dr Carlat mentions the obvious: That a major reason for the rise in psychiatric disabilities probably has to do with the changed status of psychiatric disabilities. Eligibility has been expanded, thresholds lowered.

To expand on Dr Carlat, a whole disability industry has grown up to facilitate a normally arduous application process. Clinicians and social workers routinely advise even good prognosis patients that they may qualify for disability. A fairly new specialty of disability lawyers is there to assist. Both political parties are more than happy to play along, as those on disability are not counted as being unemployed.

To tie this into a bow: Dr Carlat offers his views by way of “interpretation” rather than “repudiation.” Whitaker may not have shown cause and effect, but neither did he. Instead, Dr Carlat is presenting credible alternatives, supported by his own set of facts. This is the way to make a case.

Let’s forget for the time being whose arguments are more credible. One thing we can all agree on is at last we have a discussion going, something Whitaker wanted all along. Finally, a discussion, not a Nierenberg hissy fit.

More to come ... 

Whitaker vs Quack Psychiatry - Part II

In yesterday’s piece, I reviewed earlier posts here on Robert Whitaker’s 2010 “Anatomy of an Epidemic,” which presents a well-reasoned argument in support of the proposition that over the long term psychiatric meds may worsen - not improve - the course of mental illness. On January 13, Whitaker delivered a grand rounds to Mass General, using chapter six of his book, “A Paradox Revealed,” to make his case.

Chapter six features a 15-year study by Martin Harrow of the University of Illinois. The study was meant to identify good prognosis schizophrenia patients likely to benefit from from being weaned off their antipsychotics, but Whitaker interpreted the hard data to support his own conclusion that the patients not on antipsychotics in the study fared way better over the long haul than those on antipsychotics in all subgroups, even the bad prognosis patients.

According to Whitaker’s account of his ground rounds, prominent researcher Andrew Nierenberg of Harvard would then “share his perspective” (in the words of the grand rounds invitation) following Whitaker’s presentation.

Dr Nierenberg was one of the principal investigators of the NIMH-underwritten STEP-BD bipolar trials of the mid-2000’s and was also involved in its sister STAR*D depression trials. STEP-BD found that only one in three patients got well and stayed well on their meds over two years while STAR*D found that only one in four achieved a similar result over one year on their antidepressants.

I have heard Dr Nierenberg deliver very insightful talks at various American Psychiatric Association annual meetings, one in which he challenged the doctors in the audience to actually measure if their patients’ symptoms improved, noting they were likely to be in much worse shape than imagined.

I had occasion to talk with Dr Nierenberg in early 2007, at an NIMH-sponsored one-day conference on child bipolar in Maryland, just outside Washington DC. I was seated in an outside foyer, sipping coffee, reviewing my conference materials prior to the first session, when Dr Nierenberg took a seat next to me and graciously introduced himself. He had recently taken over as Director of the NIMH follow-up to STEP-BD, The Bipolar Trials Network.

I recall mentioning to Dr Nierenberg that it would be great if we could follow the STEP-BD patients over the next 20 years to see what happened, sort of equivalent to a Framingham study. Dr Nierenberg enthusiastically agreed. Alas, funding-funding ...

Naturally, I was looking forward to Dr Nierenberg’s response to Whitaker. On his Mad in America site, Whitaker had his own account of the response, plus downloads to Nierenberg’s slide presentation. I skimmed Whitaker’s account very briefly, then went straight to the slides.

What I saw was extremely disconcerting. From the first slide, Dr Nierenberg - or, rather his evil twin - signaled that he was not there to “share his perspective.” Rather, his presentation read, “A Refutation of The [sic] Anatomy of an Epidemic.”

Then came a Merriam Webster definition of refute, “to prove wrong” or “show to be false or erroneous.”

Stupid-stupid-stupid. Two slides in and Dr Nierenberg was already acting oppositionally defiant, with no intention of engaging in a learned and constructive dialogue. Then came a slide with a definition of repudiate. Then a pic of Sarah Palin with the caption, “repudiate.”

Was Dr Nierenberg actually comparing Whitaker to Sarah Palin? Then a Krugman quote with the word “ignorant." Was Dr Nierenberg referring to Whitaker as ignorant? Other slides portray Whitaker as being stuck in a dark ages Cartesian dualist mindset.

Ad hominem attacks of this nature are in extremely bad taste. They are also extremely unprofessional. They also feed into the stereotype of the arrogant and bullying psychiatrist who prefers lashing out to listening.

It gets worse. Further on in the slide presentation, Dr Nierenberg refers to the Harrow study as “retrospective.” Wrong - dead wrong. The study is “prospective,” which is a much higher standard than retrospective. The first sentence to the study abstract explicitly states it is a prospective study.

If Dr Nierenberg can’t even read a study abstract correctly, then, obviously, he cannot be entrusted to read the labeling to the meds he prescribes to patients. In all likelihood, Dr Nierenberg did not take the time from his very busy schedule to carefully read Whitaker’s book, much less think about it, choosing instead to hand off the assignment, together with his rebuttal, to a graduate assistant.

This type of thing goes on all the time in academia.

There are various ways of interpreting the Harrow study, and Dr Nierenberg - or his ghost writer - offers the predictable one of the patients in the study going off their meds as likely to be more well in the first place than those who stay on their meds. But this is neither a refutation nor a repudiation. Moreover, the actual data in the study most unequivocally supports Whitaker’s interpretation.

If Dr Nierenberg or any other expert is able to come up with an argument discrediting the Harrow study, we need to hear it. We really do. And it needs to be done in a thoughtful way that doesn't insult our intelligence.

(An excellent review of the Harrow study is presented by an anonymous patient blogger on Ruminations on Madness.)

Almost out of desperation, Dr Nierenberg came up with a study of a Chinese population that was not even on the point. It gets even more bizarre. Although Whitaker did not bring up antidepressants in his talk, Dr Nierenberg decided to refute and repudiate chapter eight of his book dealing with long-term antidepressant treatment. But the study Dr Nierenberg cited was not a long-term study. Yes, it tracked patients over 25 years, but the actual trial merely tested for dose efficacy over the short term.

It was as if Dr Nierenberg told his assistant, Dig up a study - any study.

What is totally weird is that the best long term trial data on antidepressants - one that shows a dismal result that supports Whitaker - comes from the very STAR*D trial that Dr Nierenberg himself was involved in.

Early in his “refutation,” Dr Nierenberg served up population statistics to rebut Whitaker’s claim of an epidemic in psychiatric disabilities, coinciding with steep rises in psychiatric prescriptions. I’m sure a crack epidemiologist could challenge Whitaker on this, and I would love to hear from one. I will compassionately spare you from Dr Nierenberg’s embarrassing presentation.

This is Dr Nierenberg’s final slide.

Really, this is sick - very sick.

Whitaker vs Quack Psychiatry - Part One

On Jan 13, 2011, journalist Robert Whitaker, author of “Anatomy of an Epidemic,” delivered a grand rounds at Mass General (which is affiliated with Harvard). Originally, Whitaker was to speak for about 40 minutes, with leading psychiatric researcher Andrew Nierenberg following with his 10-minute shared “perspective.” Then, the organizers decided to allot about 30 minutes each to the two speakers.

Background

Whitaker’s "Anatomy of an Epidemic," which came out early in 2010, makes a well-reasoned case for why psychiatric meds over the long term may significantly worsen - rather than improve - the course of mental illness. A “well-reasoned case” is hardly the same as an airtight argument, but nonetheless demands a very high level of respect.

The book placed heavy emphasis on two pieces of research:

The first, by Guy Chouinard of McGill University, pointed to the possibility of “supersensitivity psychosis” from abrupt discontinuation (or lowered doses) of antipsychotic meds, analogous to rebound symptoms observed in other classes of drugs.

In the second, Whitaker interpreted findings by Martin Harrow of the University of Illinois to indicate that over the long term, patients with schizophrenia who went off their meds had far better outcomes than patients who stayed on their meds.

Taking these studies together, along with other supporting evidence, Whitaker concluded that long-term administration of psychiatric meds is likely to result in structural changes to the brain that greatly worsens symptoms and sabotages any hope of recovery. This argument goes much further than the standard critiques involving meds and those who prescribe them.

My Blog Critiques

Over the course of October and into November, I ran about 10 or 11 pieces based on “Anatomy of an Epidemic,” and also a post-book observation from Whitaker that cited a very recent piece from Giovani Fava of the University of Bologna pointing to the possibility of “oppositional tolerance” to antidepressants.

The gist of my pieces was that Whitaker had basically made his case, which is not the same as saying I agreed with Whitaker. I carefully examined all the studies he cited, plus other research, and concluded there were other ways of interpreting the Choinard and Harrow and Fava findings, namely:

1. Supersensitivity psychosis is a valid hypothesis - and clearly there is a compelling need to prioritize this research - but even those working in the field acknowledge it is virtually impossible to distinguish a drug-effect rebound psychosis from an illness-effect psychosis. Choinard’s answer to supersensitivity psychosis was not to wean patients off of these meds (a conclusion easy to make from reading Whitaker) but to keep patients on their meds using smarter strategies (such as adding a mood stabilizer to the mix).
2. The purpose of the Harrow study was to identify types of patients with schizophrenia (say those with prior work histories) most likely to do well going off their meds, which is very different than the type of standard long-term clinical efficacy trial that Whitaker led us to believe in his book. The Harrow study identified these populations, and his findings point to a much smarter way of treating schizophrenia than current practice.
3. Fava’s “oppositional tolerance” thesis (which parallels Choinard’s supersensitivity psychosis) is very compelling, but there are many other reasons for explaining the very poor long-term results from antidepressants, such as doctors handing out these meds like candy to individuals who never should be on them in the first place.

My own interpretations in no way refute Whitaker’s, nor were they intended to. The evidence clearly justifies Whitaker in making the type of conclusions that researchers in academic journals are not allowed to make (except, of course, in creatively spinning data to make the test drug look good, but that is another story).

In my pieces, I did take Whitaker to task for failing to cite these studies in their proper context and without recognizing that there were other ways of looking at the evidence. I also cited him on a number of moving violations such as his over-reliance on antipsychiatry sources and his gratuitous cheap-shots of advocacy organizations (such as NAMI) who actually get off their asses and do things.

But I also added my unambiguous concurring voice to his $64,000 question, namely: Why do patients often seem to get worse on psychiatric meds rather than better?

Tying This Into a Bow (for Now)

As I said in the beginning of this piece, Whitaker makes a “well-reasoned” case. It is hardly airtight, but it is a far more compelling one than the extremely specious arguments that psychiatry advances for us having to stay on meds (particularly at high doses) the rest of our lives.

But even if one thinks that Whitaker is off-base, the only answer to a “well-reasoned” argument is another well-reasoned argument. Reason, even in opposition, sheds light and moves the discussion forward. We all benefit - patients, loved ones, researchers, clinicians.

What we do not want to see are petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues. Our well-being is way too important for any psychiatry thought-leader - one who has taken an oath to do no harm - to even consider such a thing.

Next: A psychiatry thought-leader delivers petty personal attacks, red herrings, misinformation, and self-serving “refutations” that fail to address the issues.

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 ...

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 ...