Tag Archives: antidepressants

SSRIs:  Minimal Effectiveness and High Risk

Last month (February 2017), the journal BMC Psychiatry published a study by James Christian  Jakobsen et al.  The study is titled Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis.

The research was a meta-analysis – i.e. it combined the findings from several earlier studies.  Here are the authors’ conclusions:

“SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.”

The authors point out that there have been previous meta-analyses assessing “the effects of SSRIs in adults with major depressive disorder”, the general conclusions of which have been that SSRI’s have a statistically significant effect on depression.  But Jakobsen et al point out that the previous studies had a number of limitations, including one or more of the following:

  • failure to use predefined Cochrane methodology in the selection of studies;
  • only including subgroups of depressed individuals;
  • failure to search all relevant databases;
  • failure to systematically assess harmful effects;
  • failure to systematically assess risk of bias in the source studies.

The authors’ objective was:

“…to conduct a comprehensive systematic review assessing the beneficial and harmful effects of SSRIs versus placebo, ‘active’ placebo, or no intervention in adult participants with major depressive disorder using our eight-step procedure for assessing evidence in systematic reviews.”

The authors’ protocol, detailing the methodology to be used, was published in advance, and can be seen here.  “The methodology was not changed after the analysis of the review results began.”

. . . . . . . . . . . . . . . .

Here are some quotes from the article, interspersed with my comments/observations.

“Independent investigators searched for eligible trials published before January 2016 in The Cochrane Library’s CENTRAL, PubMed, EMBASE, PsychLIT, PsycINFO, clinicaltrials.gov., and Science Citation Index Expanded…Trials were included irrespective of language, publication status, publication year, and publication type. To identify unpublished trials, we searched clinical trial registers of Europe and USA, websites of pharmaceutical companies, websites of U.S. Food and Drug Administration (FDA) and European Medicines Agency, and we requested the  U.S. Food and Drug Administration (FDA) to provide all publicly releasable information about relevant clinical trials of SSRIs that were submitted for marketing approval.

Participants had to be 18 years or older and have a primary diagnosis of major depressive disorder based on standardised criteria, such as DSM III, DSM III-R, DSM IV, DSM V, or ICD 10.”

Obviously this was a very comprehensive search for source studies.

“Primary outcomes

  • Depressive symptoms measured on the 17-item or 21-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), or the Beck’s Depression Inventory (BDI).
  • Remission (Hamilton <8 points; BDI <10 points; MADRS <10 points).
  • Adverse events during the intervention period which were classified as serious and non-serious adverse events. Serious adverse events were defined as medical events that were life threatening, resulted in death, disability, or significant loss of function, or caused hospital admission or prolonged hospitalization. The remaining events were classified as non-serious adverse events.

Secondary outcomes

  • Suicides, suicide attempts, and suicide ideation during the intervention period.
  • Quality of life (scale used by the trialists).

The time point of primary interest was end of treatment (defined by trialist). We also planned to report results assessed at maximum follow-up.”

. . . . . . . . . . . . . . . .

“Using our strict inclusion and exclusion criteria, a total of 195 publications/unpublished trials were identified and included. Due to multiple publications of single trials and lack of useful data, only 131 randomised clinical trials enrolling a total of 27,422 participants were included in our analyses.”

. . . . . . . . . . . . . . . .

“Estimating a meaningful threshold for clinical significance is difficult and an assessment of clinical significance should ideally not only include a threshold on an assessment scale.  Major depressive disorder affects daily functioning, increases the risk of suicidal behaviour, and decreases quality of life. Some adverse events might therefore be acceptable if SSRIs have clinically significant beneficial effects. We therefore both predefined a threshold for clinical significance and assessed the balance between beneficial and harmful effects.

As threshold for clinical significance, we chose a drug-placebo difference of 3 points on the 17-item HDRS (ranging from 0 to 52 points) or an effect size of 0.50 standardised mean difference. This has been recommended by the National Institute for Clinical Excellence (NICE) in England and has been chosen in other reviews. Nevertheless, these recommendations are not universally accepted and have been questioned. Others have suggested the following ‘rules of thumb’ regarding the standardised mean difference: 0.2 a small effect, 0.5 a moderate effect, and 0.8 a large effect. One study has shown that a SSRI-placebo mean difference of up to three points on the HDRS corresponds to ‘no clinical change’ [186]. Another valid study has shown that a SSRI-placebo difference of 3 points is undetectable by clinicians, and that a mean difference of 7 HDRS points, or a standardized mean effect size of 0.875, is required to correspond to a rating of ‘minimal improvement’[187]”

In studies of this kind, it is necessary to distinguish clinical significance from statistical significance.  This is well illustrated with a simple analogy.  Imagine a coin that has a 1% bias in favor of heads.  What this means essentially is that if one conducts a very large number of trials, each of 200 tosses, the average result per trial will be 101 heads and 99 tails: a discrepancy of 2 per 200, or 1%.  In ordinary practice, however, this coin could be considered fair for use in sporting events and other simple decision-making situations.  The 1% discrepancy is statistically significant (as opposed to a random fluctuation) but not practically significant.

Similarly, in clinical trails involving a large number of participants, a treatment effect might be statistically significant (i.e., probably not a random fluctuation), but may nevertheless be so small that it has no clinical significance.

For the purposes of the present meta-analysis, Jakobsen et al chose a 3-point difference on the 17-item Hamilton Depression Rating Scale as the threshold for clinical significance.  Their discussion of this in the above quote is self-explanatory.  Reference 187 in the above quote is to a 2015 paper by Joanna Moncrieff and Irving Kirsch.  The paper is a discussion of a 2013 study by Leucht et al, What does the HAMD mean?, which is reference 186 in the above quote.

The Leucht et al study was a meta-analysis embracing 7131 participants.  The methodology used was to compare the improvement scores that people obtained on the HDRS questionnaire with their improvement scores on the Clinical Global Impression scale (CGI-I).  The CGI is a rating scale based on a face-to-face interview and is used frequently by psychiatrists and other mental health workers in clinical and research settings to assess client improvement or deterioration.  Leucht et al found:

“The results were consistent for all assessment points examined.  A CGI-I score of 4 (‘no change’) corresponds with a slight reduction on the HAMD-17 of up to 3 points.” [Note:  the HAM-D and the HDRS are the same questionnaire.]

What this means essentially is that trained psychiatrists and other clinicians, conducting face-to-face assessments, could not detect an improvement of 3 points on the HDRS.  People who achieved an improvement of 3 points on the HDRS questionnaire were rated as “no change” on the face-to-face CGI-I.

Incidentally, five of the six authors of Leucht et al report close links to pharma.

“HF, MK and AS work full-time for Merck & Co, parent company of Organon, which provided the data for this study.  AS is also a shareholder with Merck & Co.  SL has received honoraria for consulting/advisory boards from Alkermes, Bristol-Myers Squibb, Eli Lilly, Janssen, Johnson & Johnson, Lundbeck, Medavante, Roche, lecture honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Essex Pharma, Janssen, Johnson & Johnson, Lundbeck Institute, Pfizer, Sanofi-Aventis, and Eli Lilly has provided medication for a trial with SL as the primary investigator.  PL has received honoraria for educational talks on medical ethics from AstraZeneca and Eli Lilly.”

So it seems unlikely that they would be biased towards downplaying the efficacy of antidepressant drugs.

Also incidentally, here’s an interesting quote from a general discussion of this matter in the Moncrieff and Kirsch paper:

“The small differences detected between antidepressants and placebo may represent drug-induced mental alterations (such as sedation or emotional blunting) or amplified placebo effects rather than specific ‘antidepressant’ effects.”

. . . . . . . . . . . . . . . .

Primary Outcomes

“…meta-analysis of the results of all 92 trials [that used the HDRS] showed that SSRIs versus placebo significantly reduced the HDRS score (mean difference −2.25 points…).”

In other words, there was a statistically significant reduction in average depressive “symptoms” as measured by the HDRS, but the reduction was only 2.25 points, which as discussed above, is of no clinical significance, i.e., would be rated as “no change” on the CGI-I scale.

Risk of Bias

“All trials were at high risk of bias per several bias risk domains and especially the risk of incomplete outcome data, selective outcome reporting, and insufficient blinding bias may bias our review results. Our GRADE assessments show that due to the high risks of bias the quality of the evidence must be regarded as very low. The high risks of bias question the validity of our meta-analysis results as high risk of bias trials tend to overestimate benefits and underestimate harms.  The ‘true’ effect of SSRIs might not even be statistically significant.”

In other words, the small, but statistically significant results found in the meta-analysis may simply reflect various biases that were present in the source studies, and which would inevitably bias the results of the meta-analysis.

GRADE is a protocol developed by Cochrane Training for assessing the quality of a body of evidence.  Grading of Recommendations, Assessment, Development and Evaluation.

Incomplete outcome reporting is a particularly important source of bias in these kinds of trials.  Consider a drug vs. placebo trial in which the authors have gathered ten different pieces of outcome data on each participant.  Let’s say that four of these outcome measures favor the drug and six favor the placebo.  It is very tempting for the researchers, particularly those who have a vested interest in the drug, to report the four drug-favorable measures and omit the other six.

I leave it to the reader to decide whether psychiatric research might be prone to this kind of selective reporting.

Subgroup Analyses

In trials involving people with relatively higher levels of depression (HDRS score higher than 23 points), the improvement with SSRI’s was higher than in the trials involving lower levels of depression (less than or equal to 23 points).  The mean difference was 2.69 points for the SSRI group vs. 1.29 points for the placebo group, neither of which cross the threshold for clinical significance (3 points).

Other tests for sub-group differences showed no significant differences.  These tests were:

  • comparison of different SSRI’s
  • older vs. younger participants
  • trials with washout period vs. those without
  • trials with drug/alcohol dependent participants vs. those without
  • short “treatment” period (less than 8 weeks) vs. other trials
  • dose of SSRI, below median vs. equal to or above median

Long-term Follow-up

Only six of the 131 trials reported long-term follow-up results.  The meta-analysis of all six trials showed a mean difference of 1.30 HDRS points in favor of the SSRI participants.  This is a marginally significant result statistically.  The probability that it could have been a chance fluctuation is 7%.  Additionally it is considerably below the threshold for clinical significance.

The fact that the mean difference in long-term follow-up is lower than the short-term results suggests that whatever tenuous benefits came from the SSRIs were short-lived.  It is also interesting that only 6 of 131 trials pursued any kind of long-term follow-up.

Remission and No Response

Thirty-four of the 131 trials assessed participants for remission, and 70 trials assessed for no response.  Remission was usually defined as achieving a score below 8 on the HDRS.  Response was usually defined as a 50% reduction of HDRS score.  On each of these measures, the SSRI group had a better outcome.

Jakobsen et al, however, point out that the results on remission and response need to be interpreted cautiously for the following reasons:

“1) the assessments of remission and response were primarily based on single HDRS scores and it is questionable whether single HDRS scores are indications of full remission or adequate response to the intervention; 2) information is lost when continuous data are transformed to dichotomous data and the analysis results can be greatly influenced by the distribution of data and the choice of an arbitrary cut-point; 3) even though a larger proportion of participants cross the arbitrary cut-point in the SSRI group compared with the control group (often HDRS below 8 for remission and 50% HDRS reduction for response), the effect measured on HDRS might still be limited to a few HDRS points (e.g., 3 HDRS points) or less; 4) by only focusing on how many patients cross a certain line for benefit, investigators ignore how many patients are deteriorating at the same time. If results, e.g., show relatively large beneficial effects of SSRIs when remission and response are assessed but very small averaged effects (as our results show) – then it must be because similar proportions of the participants are harmed (increase on the HDRS compared to placebo) by SSRIs. Otherwise the averaged effect would not show small or no difference in effect. The clinical significance of our results on ‘no remission’ and ‘no response’ should therefore be questioned.”

Serious Adverse Events

Forty-four trials reported data on serious adverse events.  The meta-analysis odds ratio for the SSRI vs. the placebo group was 1.37.  What this means is that “31 per 1000 SSRI participants will experience a serious adverse event compared to 22 per 1000” in the placebo group:  an excess of about eleven serious adverse events per 1000 SSRI users.  And it should be stressed that in this study, serious adverse events were defined as “…medical events that were life threatening, resulted in death, disability, or significant loss of function, or caused hospital admission or prolonged hospitalisation.”

It should also be remembered that the great majority of the trials collected no long-term data.  The eleven-per-thousand excess serious adverse events occurred during the relatively brief period of “treatment” duration, and it is reasonable to suspect that such events would be more frequent with long-term use.

It is also noteworthy that only 44 of the 131 trials reported data on serious adverse events.

Non-Serious Adverse Events

“Meta-analyses showed that the participants randomized to SSRIs versus placebo had a significantly increased risk of several [non-serious] adverse events.”

These included:  abnormal ejaculation, tremor, anorexia, nausea, somnolence, sweating, asthenia, diarrhea, constipation, insomnia, dizziness, dry mouth, libido decreased, sexual dysfunction, appetite decreased, fatigue, vomiting or upset stomach, flu syndrome, drowsiness, blurred/abnormal vision or dry eyes, nervousness, headache, dyspepsia, weight loss, central or peripheral nervous system problems, lightheadedness/faint feeling, agitation, impotence, taste perversion, etc..

Suicides, Suicide Attempts, and Suicide Ideation

“There were almost no data on suicidal behaviour, quality of life, and long-term effects.”

The limited amount of information on these matters showed no significant differences between participants randomized to SSRI’s vs. placebo on number of suicides, number of suicide attempts, or suicidal ideation.  This is particularly noteworthy in that the prescription of antidepressants is routinely defended on the grounds that they provide protection against suicide.

Readers may find this no-difference­ result puzzling, given the accumulation of anecdotal information linking SSRI use to suicides and even murder-suicides.  But it has to be borne in mind that, compared to the enormous numbers of people taking SSRIs, suicide is still a very rare event and is unlikely to occur in sufficient numbers in short studies of this kind to provide useful comparative information.

General Points

“All trials used placebo as control intervention and due to the large number of adverse events, some patients might have figured out if they received an ‘active’ intervention or not, which might question the blinding of the trials.”

“Multiple previous reviews and meta-analyses have, as mentioned in our Background, assessed the effects of SSRIs and have generally concluded that SSRIs have significant effects on depressive symptoms. However, the estimated results (and not the conclusions the review authors made) of these reviews and meta-analyses actually are in agreement with our present results and show that SSRIs do not seem to benefit patients more than a few HDRS points. This increases the validity of our present results. Furthermore, we assessed in detail the risks of serious adverse events and of non-serious adverse events and found that both were significantly increased by SSRIs.”

“Our HDRS mean differences were averaged effects. Hence, it cannot be concluded that SSRIs do not have clinically significant effects on all depressed participants. E.g., certain severely depressed patients compared with lightly depressed patients… might benefit from SSRIs even though there is no evidence backing this hypothesis. However, any clinical research result will have this ‘limitation’. Specific patients might benefit from any given intervention even though valid research results have shown that this intervention ‘on average’ is ineffective or even harmful.”

In addition, it needs to be recognized that there is no way to identify in advance which individuals will be harmed by these drugs.  So, in prescribing these drugs, psychiatrists are effectively playing Russian Roulette with one essential difference:  they’re pointing the gun at someone else’s head.

“SSRIs versus placebo seem to have statistically significant effects on depressive symptoms, but the clinical significance of these effects seems questionable and all trials were at high risk of bias. Furthermore, SSRIs versus placebo significantly increase the risk of both serious and non-serious adverse events. Our results show that the harmful effects of SSRIs versus placebo for major depressive disorder seem to outweigh any potentially small beneficial effects.”

“Per our results, we now believe that there is valid evidence for a public concern regarding the effects of SSRIs. We agree with Andrews et al. that antidepressants seem to do more harm than good. We have clearly shown that SSRIs significantly increase the risks of both serious and several non-serious adverse events. The observed harmful effects seem to outweigh the potential small beneficial clinical effects of SSRIs, if they exist. Our results confirm the findings from other studies questioning the effects of SSRIs, but are in contrast to the results of other reviews concluding that SSRIs are effective interventions for depression. However, our present analyses represent the most comprehensive systematic review on the topic and we hope it may guide clinical practice.” [Hyperlink added]

. . . . . . . . . . . . . . . .

 DISCUSSION

 If psychiatry were a bona fide medical field, a meta-analysis of this quality yielding these results would send Richter 9 shock waves through the profession.  The prescription of SSRIs for depression is probably the single most frequent activity performed by psychiatrists in their day-to-day work.  The unambiguous revelation that this activity is doing more harm than good should be generating enormous concern for psychiatry’s leadership and for the rank and file.

But the publication of this study on February 8 generated no discernible concern within the profession.  This is because psychiatry has very little interest in the scientific assessment of its “treatments”.  Psychiatry is drug-pushing, pure and simple.  The primary criteria of success are customer retention, and volume of product sold.  As long as the “patients” keep coming back for more, psychiatrists can convince themselves that they are doing good.

The fact that the “patients” have been duped by unsubstantiated assertions of chemical imbalances, and are, in many cases, addicted to the pills, are inconvenient truths that can readily be eclipsed by self-deception and in-group mutual reassurance.

. . . . . . . . . . . . . . . .

AN INTERESTING “REBUTTAL”

On February 21, 2017, Emil Karlsson, who describes himself as “a debunker of pseudoscience and steamroller of miscellaneous nonsense”, critiqued the Jakobsen et al paper on the grounds that the HDRS 3-point cut-off for clinical significance is arbitrary and excessively high.  But in fact, as we saw earlier, the threshold is based on the empirical findings that a “minimal improvement” on the Clinical Global Impression scale corresponds to an improvement of about 7 on the HDRS, and a CGI rating of “no change” corresponds to a 3-point HDRS shift.  So the threshold of 3 points, far from being too high, is actually excessively generous.  Nevertheless, the average HDRS improvement in the trials reviewed by Jakobsen et al was only 2.25 points, and the improvement in those trials that contained long-term follow-up was only 1.30 points.

FUNDING

“The work was supported by The Copenhagen Trial Unit, Centre for Clinical Intervention Research, in Denmark.”

 

 

 

Allen Frances:  Still Blaming Everyone But Himself

On May 7, Allen Frances, MD, posted an article on the HuffPost site.  The piece was titled Antidepressants Work, But Only For Really Depressed People.

Superficially, the article presents itself as a call to limit the prescribing of the so-called antidepressant drugs to severe cases; but the piece can, I suggest, be more accurately characterized as Dr. Frances’s latest attempt to distance himself, and psychiatry in general, from the pill-peddling frenzy that has characterized the profession for the past thirty or forty years

Here are some quotes, interspersed with my comments and observations.

DSM-III’S “BIGGEST MISTAKE”

“The biggest mistake in DSM III was introducing the very broad and heterogeneous category ‘Major Depressive Disorder’. This combined under one rubric what had previously been two separate and quite different presentations: 1) severe, melancholic, delusional, or incapacitating depressions, and 2) reactive to stress, mild, and often transient depressions. The result is that many people get the label Major Depressive Disorder, even though their presentation isn’t really ‘Major’, isn’t really ‘Depressive’, isn’t really ‘Disorder’. Mild sadness in reaction to stress and disappointment is lumped together with the most severe suffering known to man.”

At issue here is the old psychiatric distinction between endogenous depression and exogenous depression.  The later was conceptualized as a reaction to some external fact or circumstance, whereas the former was considered to have arisen from within the person – i.e. without any external loss or hurt.  The distinction was always problematic, in that it’s impossible to know, with certainty, that a person’s depression is not a response to some external loss, hurt, or circumstance, but the distinction was considered important within the psychiatric community generally.

In any event, the terms “exogenous” and “endogenous” went out of vogue, though the underlying concepts remained in place in DSM-III.  And, contrary to Dr. Frances’s assertion in the above quote, they remained in place as separate entities.  These were: “major depressive disorder”, and “adjustment disorder with depressed mood”.

In DSM-III, adjustment disorder is defined as “A reaction to an identifiable psychosocial stressor…”.  DSM-III made no provision for specifying severity of adjustment disorder (e.g. mild, moderate, severe), but in the text it states clearly that people may have “a more severe form of the disorder” or “only a mild form of the disorder”.  Major depressive disorder in DSM-III could be formally and explicitly coded as mild, moderate, and severe.

Now it’s no part of my agenda to defend any edition of the DSM, a document which in my view has all the scientific rigor and practical usefulness of a witch-hunter’s manual.  Rather, my purpose here is to point out that Dr. Frances’s assertion in the above quote is simply false.

Essentially what Dr. Frances is saying, or at least forcefully implying, is that since this great “error” in DSM-III, psychiatrists, misfortunate lambs that they are, have simply had no way to reflect in their “diagnostic assessments” that the individual’s depression “isn’t really ‘Major’, isn’t really ‘Depression’, isn’t really ‘Disorder’.”

And because of this truly arduous imposition, psychiatrists are constrained to lump “mild sadness in reaction to stress and disappointment” with “the most severe suffering known to man”.

It may well be that psychiatrists have been avoiding the use of “reaction to stress”, “mild” and “transient” qualifiers in their “diagnostic assessments”.  But this is emphatically not because such qualifiers were rendered impossible by DSM-III.  A much more likely explanation is that the use of these qualifiers militates against the notion, avidly promulgated by psychiatry for the past forty years, that depression, of whatever severity, is a chronic illness, (just like diabetes); a chemical imbalance in the brain, for which the “patient” must take so-called antidepressant drugs for an extended period, and possibly the rest of his/her life.  For all of this time, it has been an integral part of psychiatry’s informal, but avidly asserted, message that although depression might have been triggered by an external event, it is essentially an illness residing within the person’s neurochemistry.

But, even if we put all that aside; even if we acknowledge that Robert Spitzer and his DSM-III co-authors made a dreadful error, a critical question remains:  why did Dr. Frances himself and his DSM-IV co-authors, so uncritically follow suit?  And why has Dr. Frances not acknowledged his own perpetuation of this so-called error in the present paper?  It’s easy, and perhaps a little craven, to point fingers at the recently deceased Dr. Spitzer, when in fact, Dr. Frances himself followed precisely the same path.

And in fact, Dr. Spitzer was open enough to admit that he and his DSM-III co-workers had made a much more fundamental error.  Here’s a quote from an interview he gave to British film maker Adam Curtis.  The interview was screened by the BBC in 2007, and the 50 second excerpt can be viewed here, starting at minute 34:10.

Robert Spitzer, MD:

“What happened is that we made estimates of prevalence of mental disorders totally descriptively without considering that many of these conditions might be normal reactions which are not really disorders.  That’s the problem.  Because we were not looking at the context in which those conditions developed.”

Adam Curtis:

“So you have effectively medicalized much of ordinary human sadness, fear, ordinary experiences, you’ve medicalized them.”

Spitzer:

“Uh, I think we have, to some extent.  How serious a problem it is is not known.  I don’t know if it’s twenty percent, thirty percent, I don’t know.  But that’s a considerable amount if it is twenty or thirty percent.”

. . . . . . . . . . . . . . . .

Back to the Huffington Post piece.

“Drug companies jumped on the opportunity to peddle a pill for every problem and misleadingly described all depressions as a chemical imbalance requiring a chemical solution. Treatment studies that previously showed clear superiority of medicine over placebo for severe depression showed little or no superiority with patients whose depression was mild or questionable. And biological marker studies that showed promise in tagging severe depression came up empty with the watered down Major Depressive Disorder.”

There it is again.  Those mean old opportunistic drug companies!  How could one ever trust them?

But again, a major distortion of reality.  Drug companies can’t sell these products without FDA approval, and a physician’s prescription.  It was psychiatrists who created and promulgated the questionable research that elicited FDA approval and legitimized the wholesale use of these products.  Admittedly, these psychiatrists were handsomely paid by pharma, but they were not constrained.  Dr. Frances is surely familiar with this process.  In 1995, he and his two colleagues Drs. John Docherty and David Kahn, reportedly accepted $515,000 from Johnson & Johnson to write “Schizophrenia Practice Guidelines”, which blatantly promoted Risperdal (risperidone), a drug manufactured by Johnson & Johnson.  For a full and compelling account of this sordid tale, see Paula Caplan’s very thorough exposé here.

The notion that psychiatric research would clearly support the use of the drugs and would identify biological markers for depression, if only the “mild or questionable” depressions were excluded, is fanciful.  Depression has been extensively researched for decades, by psychiatrists, highly motivated by pharma largesse to find significant positive results.  These studies routinely report that “diagnoses” were confirmed by scrupulously careful evaluations using psychiatric interviews and validated screening tools.  So why would there by “questionable” cases in the studied samples?  In fact, in his Introduction to DSM-IV (1984), Dr. Frances explicitly acknowledged DSM-III’s contribution in this area.

“The third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) represented a major advance in the diagnosis of mental disorders and greatly facilitated empirical research.  The development of DSM-IV has benefited from the substantial increase in the research on diagnosis that was generated in part by DSM-III and DSM-III-R.” (p. xviii) [Boldface added]

An identical passage was included on page xxvi in DSM-IV-TR six years later (2000)

And furthermore, individuals whose depression is mild can be eliminated readily and legitimately from a study by limiting the scope to moderate and severe cases.

PSYCHIATRY DID PROMOTE THE CHEMICAL IMBALANCE THEORY

And what are we to make of Dr. Frances’s assertion that the drug companies “…misleadingly described all depressions as a chemical imbalance requiring a chemical solution”? In fact, it was psychiatry who promoted the chemical imbalance hoax.  Pharma certainly tagged along, with their blatantly false commercials, but psychiatry could have stopped this fraudulent inanity in its tracks at any time, by issuing a clear and definitive press release disavowing the hoax, and by filing a formal complaint of false advertising with the Federal Trade Commission.

But psychiatry took no such action.  Psychiatry blatantly, and without compunction, foisted this falsehood on their “patients”, on the public, and on other practitioners – knowing it to be false – for the purpose of promoting their own guild interests, and selling more drugs.  It is simply beyond comprehension that Dr. Frances continues to try to slough off the responsibility for this hoax, this gross violation of the public trust, onto his erstwhile pharma benefactors.

If Dr. Frances has any residual doubts as to psychiatry’s role in the dissemination of this falsehood, he might usefully take a look at Terry Lynch’s book Depression Delusion or my post Psychiatry DID Promote the Chemical Imbalance Theory

Or … he might want to revisit something he himself wrote in 1998.  Here’s a quote from Am I Okay? by Allen Frances, MD, and Michael B First, MD:

“Depression is really no different than hypertension.  Medicines that treat high blood pressure are taken to reestablish the body’s ability to maintain a normal blood pressure.  Antidepressants work in the same way—restoring brain neurochemistry to its original natural state.  In contrast to drugs like heroin and cocaine, which make virtually everyone feel euphoric, an antidepressant does nothing for a person without depression except produce unpleasant side effects.  There is no street market for antidepressants and they are not addictive.  Finally, in the same way that it would be ludicrous to think that someone can simply will their elevated blood pressure down to normal, true grit is not by itself sufficient to cure clinical depression.” (p 49-50)  [Emphasis added]

Incidentally, Dr. Frances’s promotion of the now defunct chemical imbalance theory of depression in the above quote is particularly interesting in the light of the statement made by the very eminent psychiatrist Ronald Pies, MD in his April 2014 article Nuances, Narratives, and the Chemical Imbalance Debate:

“To the extent the ‘chemical imbalance’ notion took hold in our popular culture, it was due mainly to distorted or oversimplified versions of the catecholamine hypothesis. These were often depicted in drug company ads; pop psychology magazines; and, in recent years, on misinformed Websites and blogs. In short, the ‘chemical imbalance theory’ was never a real theory, nor was it widely propounded by responsible practitioners in the field of psychiatry.”

Dr. Pies, meet Dr. Frances.

With regards to Dr. Frances’s assertion that there is no street market for antidepressants, here is a letter in the February 2007 issue of the American Journal of Psychiatry.  The letter is from Greg Tarasoff, MD, a psychiatrist, and Kathryn Osti, and is titled Black-Market Value of Antipsychotics, Antidepressants, and Hypnotics in Las Vegas, Nevada. The letter reports that, at that time, antidepressants were selling on the street for $3-$5 per dose.

Also, here’s a 2013 article from globalnews.ca, Toronto, which describes an active street market in Wellbutrin.  The article was written by Jennifer Tryon and Nick Logan, and it reports that Wellbutrin is referred to as “the poor man’s cocaine”.

I realize, of course, that Am I Okay was written before these articles, but here are two studies that predate the book:

Abuse of Amitriptyline by Cohen, Hanbury, and Stimmel: JAMA, Sept 1978:

“A survey of 346 persons enrolled in a methadone maintenance program showed that 86 (25%) had admitted taking amitriptyline with the purpose of achieving euphoria.”

And Identification of misused drugs in the clinical laboratory. I. Tricyclics, by Vasiliades, J; Clinical Biochemistry, February 1980:

“A systematic approach evaluating the abuse of tricyclic drugs in the hospital emergency room from the laboratory point of view is presented…Increasing misuse of tricyclic antidepressants requires that the clinical laboratory have a systematic approach to identify and confirm the presence of these drugs in emergency room patients.” [Emphasis added]

. . . . . . . . . . . . . . . .

FRANCES PROMOTED THE DRUGS

Back to Am I Okay?  Here’s a quote in which Drs. Frances and First promoted the drugs as “very effective” in the treatment of “major depressive disorder”:

“For those suffering from Major Depressive Disorder, antidepressant medications are very effective—the overall odds that an antidepressant treatment will work eventually are probably at least 90 percent.  But you have to be patient and forbearing along the way.  It usually takes at least several weeks for the medication to begin working, and a couple of months before it has reached its maximum effect.  It might also take time and effort to find the most effective medication for you and to determine its proper dose.  Some people must endure several trials of different antidepressants until they find the one that is a winner for them.  To give you some perspective, two thirds of depressed patients will have a good response to the first medicine that is tried. For those who do not respond initially, the odds of a second antidepressant working are about fifty-fifty—this gets us to about 80 percent total response rate.  If you have still not yet responded after two tries, a third or fourth or even a fifth try may be necessary to find the medicine or combination of medicines that will eventually work.  The good news is that there are close to thirty available antidepressants on the market and new ones are being developed all the time.  Hopefully sooner, but almost certainly eventually, one of these or some combination will work for you.

The use of antidepressant medication has risen dramatically over the past several years, but many people who might benefit have misconceptions that make them reluctant to give one a try.  One common concern is that the changes resulting from antidepressant use are artificial and, by implication, somehow illegitimate.  Others worry that they will become physically dependent on antidepressants in the same way that a heroin addict cannot function without his daily fix.  Yet others feel that having to rely on antidepressant medications to maintain one’s mood (and productivity) represents a weakness in moral fiber—that you should be able to get rid of the depression by sheer will power alone.” (p 49)

There are several noteworthy points in this quote.

Firstly, Dr. Frances does not limit his assertions to cases of “severe, melancholic, delusional, or incapacitating depressions“, even though such options were available within the psychiatric “diagnostic” system.  The phrase “…those suffering from Major Depressive Disorder” clearly embraces mild, moderate, and severe unless otherwise delineated.  In fairness to Dr. Frances, he does acknowledge elsewhere in the text that the drugs are not always necessary, but his assertions in this regard are generally less compelling, e.g., “antidepressant medications are probably overused.” (p 50) [Emphasis added]

Secondly, the tone of the quote with regards to taking the drugs is upbeat and optimistic.  The drugs “…are very effective”; “the odds of successful treatment…are probably at least 90 percent”; “…there are close to thirty available antidepressants on the market…”; “…one of these or some combination will work for you.”

Thirdly, the authors acknowledge that antidepressant use has risen “dramatically”, but then go on to encourage further use.

Fourthly, there are clear efforts on the part of the authors to undermine people’s resistance to drug-taking. The authors dismiss concerns that the effects of the drugs are “artificial” and that the drugs might be addictive.  Bearing in mind that the book was written for general audiences (A Layman’s Guide to the Psychiatrist’s Bible), the assertion that antidepressants restore “…neurochemistry to its original natural state”, with its almost Edenic connotations, is nothing short of outrageous.

And incidentally, here’s another quote from the same chapter:

“ECT is a terrifically effective treatment  that is also relatively safe considering the great benefits that can often be gained.  ECT is especially useful for psychotic mood disorders, people who need a really fast response, medication nonresponders, and for those who cannot tolerate antidepressant medication.  Electroconvulsive therapy has a higher response rate (80 to 90 percent versus the 65 to 70 percent achieved by medication combinations) and also works more rapidly.  However, it has the disadvantage of providing fewer clues as to what type of medication is likely to work to prevent recurrences in the maintenance phase.  Due to misguided fears, ECT has been most typically considered a treatment of last resort when nothing else works.  It probably deserves to be used earlier and more often.” (p 51-52)

Note that the success rate of antidepressants which on page 49 was given as “at least 90 percent”, is now, two pages later, given as “65 to 70 percent”.

Note also that Dr. Frances is advocating an expansion of the use of high voltage electric shocks to the brain as a “treatment” for depression, and makes no mention of the permanent memory damage that this “treatment” entails.

. . . . . . . . . . . . . . . .

Back to the HuffPost article:

“Critics of medication jumped on this to argue misleadingly that depression is a myth and/or that medication treatment for depression doesn’t work.”

I don’t know of anyone on this side of the debate who argues that “depression is a myth”.  I myself argue – as do a great many others – that depression is not an illness.  But depression is real, and I don’t believe that I’ve ever heard anyone suggest otherwise.  My own position is that depression is the natural human reaction to loss or to ongoing hardship/drudgery, and that severe depression is the normal reaction to a major loss or to ongoing hardship/drudgery that is particularly arduous.  It is not something that needs to be “treated”; rather, it can be alleviated, either by supporting individuals through their loss, or actively helping them identify and extricate themselves from the depressing circumstances.  What the pills do, in some cases, is provide an altered mental state, which some people find preferable to the depression.  But the pills produce no lasting benefits, and usually do a great deal more harm than good.  The issue here is not whether people should or shouldn’t take these pills.  That’s each person’s individual choice.  The issue is psychiatry pushing these dangerous serotonin-disruptive chemicals on people, under the pretense that they have an illness, for which the pills are an effective and safe treatment.

. . . . . . . . . . . . . . . .

At this point in the article, Dr. Frances introduces Mark Kramer, MD, PhD.  Dr. Kramer restates and elaborates on some of the points made by Dr. Frances, who in turn closes the article with some concluding remarks, including:

“The next point seems too obvious to be stated, but nonetheless desperately needs stating. Only people who are clearly clinically depressed and clearly need antidepressants should be included in research studies and should be taking antidepressants in everyday clinical practice. Depression has been too carelessly diagnosed- encouraged by the loose DSM definition, by Pharma’s desire to push product; by rushed doctors; and by people’s hope for a quick fix for life’s problems.”

It should be noted that the term “clinically depressed”, despite its widespread usage, has no formal meaning in psychiatry.  In practice, it is used to mean having a “diagnosis” of major depressive disorder or dysthymia, but because of the medical connotations of the word “clinical”, it is also used to convey and promote the notion that depression is an illness.  So Dr. Frances is telling us that only people who clearly meet the criteria for major depressive disorder or dysthymia, and who clearly need antidepressants, should be taking antidepressants.  But this is nothing more than an empty platitude.  What’s the alternative?  Take antidepressants even though you don’t really need them?  Who is suggesting that? And anyway, wasn’t the whole point of the DSM to provide rigorous definitions of the various “mental disorders”?  Hasn’t this been the standard psychiatry patter since DSM-III?  In fact, here’s the opening paragraph from the Introduction to Dr. Frances’s own DSM-IV:

“This is the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, or DSM-IV.  The utility and credibility of DSM-IV require that it focus on its clinical, research, and educational purposes and be supported by an extensive empirical foundation.  Our highest priority has been to provide a helpful guide to clinical practice.  We hoped to make DSM-IV practical and useful for clinicians by striving for brevity of criteria sets, clarity of language, and explicit statements of the constructs embodied in the diagnostic criteria.  An additional goal was to facilitate research and improve communication among clinicians and researchers.  We were also mindful of the use of DSM-IV for improving the collection of clinical information and as an education tool for teaching psychopathology.” (p xv)

and later, concerning DSM-III:

“DSM-III introduced a number of important methodological innovations, including explicit diagnostic criteria, a multiaxial system, and a descriptive approach that attempted to be neutral with respect to theories of etiology.” (p xvii-xviii)

So if the problem is “loose DSM definitions”, Dr. Frances needs to direct at least some of the responsibility for the present state of affairs in his own direction; firstly for drafting a document that slavishly followed the errors he now ascribes to DSM-III, and secondly for  falsely hyping DSM-IV in that edition’s Introduction.

In should also be noted, that the “diagnostic” definitions in all editions of the DSM are notoriously vague and “loose”.  But in addition, Dr. Frances’s own DSM-IV added an entire layer of looseness:

“The specific diagnostic criteria included in DSM-IV are meant to serve as guidelines to be informed by clinical judgment and are not meant to be used in a cookbook fashion.  For example, the exercise of clinical judgment may justify giving a certain diagnosis to an individual even though the clinical presentation falls just short of meeting the full criteria for the diagnosis as long as the symptoms that are present are persistent and severe.” (p xxiii) [Emphasis added]

How short is “just short”?  What duration would be considered persistent?  In the case of “major depressive disorder”, we know that “persistent” means two weeks!

Dr. Frances tells us that depression (by which he clearly means the mythical illness) has been too carelessly diagnosed by

– pharma’s desire to push product;
– rushed doctors (note, not specifically psychiatrists); and
– people’s hope for a quick fix for life’s problems

In short:  everyone is to blame for the drug-pushing except psychiatry; that dauntless and noble pillar of compassionate rectitude, standing valiantly alone against the surging tide of venality, corruption, disease-mongering, slovenliness, and disempowerment that characterizes all the other players in this epic tragedy.

The notion that the loose definitions, the inexorable expansion of the “diagnostic” net, and the broadening of “indications” for the drugs were errors, is simply not credible.  If these were errors, then psychiatrists must surely be a most inept group of people.  Rather, these developments were, and still are, an integral part of psychiatry’s plan to expand its scope and to strengthen its hegemony.  And this plan, in the implementation of which Dr. Frances played a leading part, is still in place.  Psychiatry, with the help of their pharma allies, is actively promoting early screening for various “diagnoses”.  Active steps are being taken to have mental health services embedded in every school and in every GP’s office.  Children as young as three years old are being given major tranquilizers to “treat” temper tantrums, and vulnerable individuals in nursing homes, foster care, and group homes are being drugged at unprecedented levels.

If Dr. Frances genuinely wants to distance himself from this institutional degeneracy, he must first acknowledge the role that he himself played in its creation.

THE FUNDAMENTAL PROBLEM

Important as all these issues are, there is a fundamental, over-riding issue that is much more critical.

The assertion that the so-called antidepressants are being over-prescribed implies that there is a correct and appropriate level of prescribing towards which reformative efforts should be directed.

And this premise is false, for three reasons.  Firstly, because depression, regardless of its severity or persistence, is not an illness which needs to be treated with medication.  Secondly, because the drugs, despite the psychiatric-pharma hype, are not particularly effective in ameliorating depression.  And, thirdly, because these serotonin-disruptive drugs have a wide range of adverse effects, the seriousness of which has been routinely downplayed by pharma and by psychiatry.

The widespread and increasing use of the so-called antidepressant drugs is certainly a matter for concern, as is the assignment of depression “diagnoses” to more and more people.  But these problems stem directly and inevitably from the fact that psychiatry invented these spurious illnesses and generated the bogus research to legitimize the use of the pills as safe and effective “treatments”.  Given the inherent vagueness of the criteria and the absence of an identified and confirmable biological pathology, it was inevitable and predictable that “diagnosing” and pill-pushing would increase. To put the matter briefly, there is no way to determine who has the illness called depression and who doesn’t, because no such illness exists.  Psychiatry invented this entity, concocted an inane checklist of “symptoms” to create the appearance of medical legitimacy, peddled the pills with abandon, and reaped the profits.

Allen Frances’s bemoaning the “over-prescribing” at this late stage in the game is not only hypocritical.  It also serves to distract his readers from the real issue:  that psychiatry is, at its very core, an enormous and destructive hoax, and cannot be saved from its own self-serving excesses by these kinds of platitudinous calls to clean house.

Klonopin and prozac withdrawal

This post was submitted by a reader.

 

 

 

 

 

It’s been almost 3 months since I have ingested any antidepressants or benzos. Almost died after drinking a large amount of vodka with the daily does of pills. Went to a rehab for a month and have been clean since. This is after over 27 years of benzos and prozac. I am 60 years old and am finally coming a awake. The Withdrawals, notably the restless leg and horrible cramping have been horrid at night, but I am totally committed to staying off the evil pills! Thanks for listening!

 

A Reader

The Germanwings Crash:  Flying Under the Influence

On March 24, 2015, a twenty-seven-year-old German pilot named Andreas Lubitz flew an Airbus A 320 into a French mountainside, killing himself and the 149 other people on board.  Mr. Lubitz was co-piloting the flight, and he caused the aircraft to crash by locking the pilot out of the flight deck and setting the autopilot to descend to 100 feet.

During the descent, he was contacted by civilian and military traffic controllers, and by the crew of another aircraft, but he made no response.  He also ignored repeated and increasingly urgent requests from the captain to be readmitted to the flight deck.

In an earlier flight on the same day, Mr. Lubitz had set the autopilot to descend from 35,000 feet to 100 feet, and returned it to the original setting after three seconds.  Investigators suggested that this earlier maneuver may have been a rehearsal for the subsequent murder/suicide.

INVESTIGATION REPORT

The crash was investigated by the French Bureau d’Enquêtes et d’Analyses (BEA), who issued their final report on March 13, 2016.  Here are some of the findings from this report.

Mr. Lubitz had become depressed in August 2008 and had received psychiatric treatment, including psychiatric drugs, between November 2008 and July 2009.

Mr. Lubitz had been rated “above standard” on professionalism and skill by his instructors and examiners.

Mr. Lubitz’s private physicians refused to be interviewed by the BEA.

On February 24, 2015, four weeks before the murder/suicide, Mr. Lubitz received his first prescription of mirtazapine from his psychiatrist.  Mirtazapine, which is marketed in the US as Remeron, is an antidepressant with serotonergic activity.  Adverse effects include suicide risk, apathy, and aggression (RxList).  In the US, mirtazapine carries a suicide risk black box warning.

On March 16, 2015, eight days before the murder/suicide, Mr. Lubitz received further prescriptions of Escitalopram, Dominal, and Zolpidem from his psychiatrist.  Escitalopram, which is marketed in the US as Lexapro, is an SSRI antidepressant, and also carries a suicide black box warning.  Dominal (prothipendyl) is described as having a weak anti-psychotic potency (Wikipedia, translation from German), and is used to reduce restlessness and agitation.  Zolpidem (marketed as Ambien) is a sleeping pill.

In an email sent to his psychiatrist in March 2015, Mr. Lubitz stated that he had taken additional drugs:  Mirtazapine (15mg) and Lorazepam (1 mg).

Toxicological examination of the co-pilot’s human tissue found at the crash site detected the presence of citalopram and mirtazapine (both anti-depressants), and zopiclone (a sleeping pill).

EXPRESSIONS OF CONCERN

Since the publication of the BEA Final Report, concerns have been expressed by various individuals and groups, including bereaved relatives of the victims.  In general, these concerns have focused on the following issues:

  • That Lufthansa (the parent airline) should have done more to protect their customers.
  • That because of medical confidentiality, Mr. Lubitz was able to hide his depression and his use of antidepressant drugs from his employer.
  • That several of the doctors involved in Mr. Lubitz’s care refused to provide information to the BEA investigators.
  • That Mr. Lubitz had managed to keep his pilot’s license, despite his history with depression and psychiatric drugs.

But there has been relatively little attention focused on what is, at least in my view, the most glaring and pertinent aspect of the matter:

That Mr. Lubitz was flying a commercial aircraft under the influence of powerful psychiatric drugs that have long been associated with murder/suicides.

LINKS BETWEEN MURDER/SUICIDE AND SEROTONIN DISRUPTIVE DRUGS

On September 14, 1989, a few weeks after he had started taking Prozac (the first SSRI), Joseph Wesbecker, of Louisville, Kentucky, went on a rampage at his place of employment, killing eight and wounding twelve others, before taking his own life.  Eli Lilly, the makers of Prozac, settled the subsequent litigation for an undisclosed sum that was said to be “mind boggling” (Joseph Glenmullen, Prozac Backlash, 2000, p. 176).  In the interim years, there have been numerous similar incidents.

It is now 36 years since Drs. Teicher, Glod, and Cole wrote:

“Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these patients had ever experienced a similar state during treatment with any other psychotropic drug.” American Journal of Psychiatry, 1990. [Fluoxetine, marketed as Prozac, is an SSRI]

Over the next two years, similar reports appeared in the New England Journal of Medicine, Journal of the American Academy of Child and Adolescent Psychiatry (here) and (here), Journal of Family Practice, American Journal of Psychiatry (here) and (here), Archives of General Psychiatry, Human Psychopharmacology, and the Lancet.

And similar tragic incidents have occurred with more recent drugs that tamper with the brain’s serotonin systems.

Nevertheless, psychiatry, to its eternal shame, has made no attempt to study definitively the role that psychiatric drugs play in these matters.  Instead, there has been spin:  more “treatment” is needed for “mental illness”; these drugs are safe when “properly prescribed”; the benefits outweigh the risks; etc…

It was even stated, by Connecticut Assistant Attorney General, Patrick B. Kwanashie, in the wake of the Sandy Hook murders/suicide that it would not be wise to divulge the drugs found in the shooter’s post-mortem examination, for fear that it would “… cause a lot of people to stop taking their medications.”

Even the horrific events of March 24, 2015, in the French Alps have been insufficient to jar psychiatry from its sordidly self-serving, guild-defensive silence into something resembling common decency.  It took ten minutes for the Airbus to descend from 38,000 feet to its crash site on a French mountain; ten minutes of indescribable terror for 149 innocent men, women, and children.  It is time – indeed it is long past time – for psychiatry to acknowledge the role that these pills are playing in these tragedies, to conduct a definitive study of this matter, and to publicize the problem honestly and prominently.

. . . . . . . . . . . . . . . .

On February 26, 2016, David Jolly, a member of the US House from Florida’s 13th District, introduced a bill directing the Department of Veterans’ Affairs to complete a publicly available review of the deaths of all veterans who died by suicide during the preceding five years.  The review would include a list of all medications prescribed to, and found in the system of, such veterans at the time of their deaths.

On March 7, the bill was sent to the Subcommittee on Health.  It will be interesting to watch its progress or lack thereof.  It will be interesting to see if politicians have more courage to buck their pharma paymasters than psychiatrists.  They certainly couldn’t have less.

Exploiting The Placebo Effect:  Deceiving People For Their Own Good?

Readers may remember that a few weeks ago I became involved in an online debate with the very eminent and scholarly psychiatrist Ronald Pies, MD.  That exchange was initiated by a post I wrote concerning a paper on the chemical imbalance theory that Jeffrey Lacasse, PhD, and Jonathan Leo, PhD, had published in the Behavior Therapist in October 2015.  In that paper, Drs. Lacasse and Leo had drawn attention to certain aspects of Dr. Pies’ work, but they had also focused some attention on Daniel Carlat, MD, psychiatrist, and author of Unhinged: The Trouble with Psychiatry – A Doctor’s Revelations about a Profession in Crisis.

The subsequent issue of the Behavior Therapist contained replies from Dr. Pies and Dr. Carlat, together with a counter-response from Drs. Lacasse and Leo.

There was nothing new in Dr. Pies’ letter, so I won’t dwell on that here, but Dr. Carlat’s letter warrants, I think, some discussion.

As mentioned above, Dr. Carlat is the author of Unhinged (2010).  This is an interesting work:  a kind of “confessions of a reformed psychiatrist” book.  I read it when it came out, and was impressed by Dr. Carlat’s candor and courage.  I wrote a review on the work on October 30, 2010, and have quoted from it on a number of occasions in the subsequent years.  I had formed the opinion that Dr. Carlat was a psychiatrist who had recognized the hoax, and was doing what he could to expose it.

CARLAT’S INTERVIEW ON NPR

In July 2010, Dr. Carlat gave an interview on NPR concerning his book, and it was on comments that he had made in that interview that Drs. Lacasse and Leo had focused in their original article.  Drs. Lacasse and Leo provided three quotes from the interview.  Here’s the full passage from which they quoted.  (The interview was conducted by Dave Davies):

“DAVIES: How much do we know about how psychological medications actually work?

Dr. CARLAT: Well, we know both a lot and very little, and the way in which we know a lot is that through clinical trial studies, in which patients are randomly assigned to a medication versus a placebo sugar pill, we know how effective these medications are, in other words how much of an advantage medication has over a placebo.

And that varies from medication to medication. It tends to be a very minimal advantage for antidepressants when treating depression. It tends to be a higher advantage when treating schizophrenia.

But on the other hand, what we don’t know is we don’t know how the medications actually work in the brain. So whereas it’s not uncommon – and I still do this, actually, when patients ask me about these medications, I’ll often say something like, well, the way Zoloft works is it increases the levels of serotonin in your brain, in your synapses, the neurons, and presumably the reason you’re depressed or anxious is that you have some sort of a deficiency.

And I say that not because I really believe it, because I know that the evidence isn’t really there for us to understand the mechanism. I think I say that because patients want to know something, and they want to know that we as physicians have some basic understanding of what we’re doing when we’re prescribing medications.

And they certainly don’t want to hear that a psychiatrist essentially has no idea how these medications work.

DAVIES: But that’s pretty close to the truth?

Dr. CARLAT: Unfortunately, it is close to the truth. We’re in a paradoxical situation, I think, where, you know, we prescribe medications that do work, according to the trials, and yet as opposed to essentially all other branches of medicine, we don’t understand the pathophysiology of what generates mental illness, and we don’t understand exactly how our medications work.

DAVIES: And it can be reassuring if you’re prescribing a medication to tell someone, well, there’s really a biological origin of your difficulty here, and we can treat it with – by treating the biology.

Dr. CARLAT: Right, which is exactly why I still tell patients that at times. But I think, you know, one thing that has happened is that because there’s been such a vacuum in our knowledge about mechanism, the drug companies have been happy to sort of fill that vacuum with their own version of knowledge so that usually, if you see a commercial for Zoloft on TV, you’ll be hearing the line about serotonin deficiencies and chemical imbalances, even though we don’t really have the data to back it up.

It becomes a very useful marketing line for drug companies, and then it becomes a reasonable thing for us to say to patients to give them more confidence in the treatment that they’re getting from us. But it may not be true.

DAVIES: Right. Well, I certainly want to talk a lot more about what drug companies do to market their products, but, you know, help us understand the distinction between the kind of scientific knowledge we have about the brain and its reaction to psychological medications, as opposed to, you know, treatments for cardiac disorders or vascular disease.

Dr. CARLAT: Sure. And – so for example, I’ll take the example of a medication like Zoloft, which is in the class of SSRI, which is specific serotonin reuptake inhibitor.

And as the name implies, what we think these medications do is they prevent the neurons of the brain from sort of vacuuming up the excess chemicals and neurotransmitters that the neurons generate so that if the depression or anxiety disorder is due to a deficiency of a chemical, a reuptake inhibitor would act by pumping out or allowing the neuron to pump out more neurotransmitter, thereby famously balancing the chemicals.

And the problem is that we don’t have any direct evidence that depression or anxiety or any psychiatric disorder is actually due to a deficiency in serotonin because it’s very hard to actually measure serotonin from a living brain.

And any efforts that have been made to measure serotonin indirectly, such as measuring it in the spinal fluid or doing postmortem studies, have been inconclusive. They have not shown conclusively that there is either too little or too much serotonin in the fluids. So that’s where we are with psychiatry.

And then your other question was: How does that differ from some of the other medical fields? Well, for example, in cardiology we have a good understanding of how the heart pumps, what electrical signals generate activity in the heart.

And due to that understanding, we can then target specific cardiac medications to treat problems like heart failure or heart attacks, again based on a pretty well-worked-out knowledge of the pathophysiology – not perfect, but pretty well worked out.

DAVIES: Whereas – to draw an analogy to psychiatry, it might be like saying, well, if nitroglycerin eases your chest pains, then we conclude that your heart problem is a deficiency of nitroglycerin.

Dr. CARLAT: Exactly, or if we find that opiate medications treat pain in general, we might conclude that pain is a opiate or narcotic-deficiency illness, whereas in fact we know that pain is not an opiate-deficiency illness. It’s a symptom that can be caused by many, many different pathologies throughout the body.”

THE CRITIQUE FROM DRS. LACASSE AND LEO

Drs. Lacasse and Leo challenged some of the statements Dr. Carlat made in this interview, and pointed out:

“So Carlat is aware of the clinical trials, which essentially refute the serotonin theory, yet still tells patients that they have a serotonin imbalance.”

and

“The simple alternative would be to tell patients the truth—that the pathophysiology of depression is unknown and that we have no idea how SSRIs work.”

In the NPR interview, it is clear – or at least is seems clear to me – that Dr. Carlat admitted that he routinely deceives his clients on these issues, and in that regard, the assessment and suggestion put forward by Drs. Lacasse and Leo seem correct and appropriate.

CARLAT’S RESPONSE

But in his response in the Winter issue of the Behavior Therapist, Dr. Carlat denies any deception on his part.  Here’s a quote from his letter:

“In one section of the article, they accuse me of making deceptive statements to my patients about how antidepressants work. I deny this accusation. In talking to patients  I simplify neurobiological concepts, using a shorthand to describe, in a simplistic way, some common theories of mental illness. I do this to enhance the placebo effect—which accounts for a significant portion of the overall effectiveness of antidepressants.  Two of the most crucial components of the placebo effect are fostering positive expectations of success and reinforcing the medical ritual of pill-taking (Kaptchuk et al., 2010; Leuchter, 2014). In order to augment my patients’ response to antidepressants, I will say something like, ‘This is a very effective medication, you should take this pill every morning, and you will begin to feel better within a couple of weeks.’ If a patient asks me how the medication works, I will respond with, ‘We’re not completely sure, but it has something to do with increasing levels of neurotransmitters like serotonin or norepinephrine—basically, these pills rebalance certain chemicals in the brain.’

There is nothing deceptive about such statements. While we don’t understand exactly what serotonin’s role is, we have some educated hypotheses. A recent review of serotonin and depression identifies 14 known serotonin receptor subtypes. When antidepressants bind to these receptors, a variety of chemical processes unfold, affecting levels of dopamine, norepinephrine, acetylcholine, cortisol—and yes, serotonin. While it isn’t clear exactly how these chemical cascades alleviate depression or anxiety, it is clear that effective antidepressants exert their actions via shifts in the brain’s biochemical milieu—and that serotonin is one of the central players in the drama (Kohler et al., 2015).

The authors, unfortunately, do not seem to be interested in scientific evidence.  In their role as the serotonin thought police, they brook no uncertainty: the serotonin theory is discredited, full stop.”

COUNTER-RESPONSE FROM DRS. LACASSE AND LEO

In their response, Drs. Lacasse and Leo pointed out very clearly that in the NPR interview, Dr. Carlat had admitted that he deceived his clients:

“…we don’t believe we’re alone in thinking it’s objectionable to tell patients something you don’t believe yourself.”

Drs. Lacasse and Leo also cited a passage in Dr. Carlat’s book Unhinged where he made similar admissions.  They then concluded their response to Dr. Carlat with a  paragraph that ought to be carved in stone and displayed prominently in every psychiatric training center in the world:

“We don’t think scientific truth is so flexible, and disagree with shaping it for purposes convenient to the prescriber (e.g., to get patients to take medication, or to reassure the patient of the prescriber’s expert knowledge). Dr. Carlat also writes that he boosts the placebo effect by telling patients that SSRIs are ‘a very effective medication’ (Carlat, 2015; this issue, p. 262). Fournier et al. (2010) demonstrated a Number-Needed-to-Treat (NNT) of 11 for severely depressed patients. In other words, when prescribing to 11 severely depressed patients, a prescriber would expect 1 to have an impressive short-term response as compared to placebo. Given the existence of such data, we question the accuracy of claiming that antidepressants are ‘very effective’ (see also Weitz et al., 2015).”

And to which I would add the following observations”

1. It is clear that, at least in Dr. Carlat’s practice, the chemical imbalance hoax is still alive and well.

2.  Deceiving clients “to enhance the placebo effect” betrays an extraordinary level of condescension, and a fundamental misunderstanding of how best to help people who are experiencing problems of thinking, feeling, and/or behaving.

3.  In the absence of evidence of efficacy, “fostering positive expectations of success” is a sham, essentially similar to the kind of hype used by traveling snake-oil peddlers in the late 1800’s.

4.  “Reinforcing the medical ritual of pill-taking” is a euphemism for drug-pushing.

5.  The notion that antidepressants “rebalance certain chemicals in the brain” is a hoax. It is just as likely  – in fact, arguably more likely – that these drugs disrupt the normal chemical functions in the brain.  Cocaine is a serotonin reuptake inhibitor (SRI), but I have never heard claims that it rebalances brain chemicals.  In fact, in most contexts, such a claim would be considered ridiculous.

6.  Dr. Carlat’s characterization of Drs. Lacasse and Leo as “the serotonin thought police” is just one more example of entrenched psychiatry’s marginalization of its critics. They can’t gainsay our arguments, so they resort to personal attacks.  In addition, there is an enormous irony in a psychiatrist using the epithet “thought police” to express censure, when it is psychiatry itself that routinely incarcerates and forcibly drugs and shocks people on the grounds that their thoughts and speech don’t conform to psychiatry’s standards of normality.

The Link Between Psychiatric Drugs and Violence

One of psychiatry’s most obvious vulnerabilities is the fact that various so-called antidepressant drugs induce homicidal and suicidal feelings and actions in some people, especially late adolescents and young adults.  This fact is not in dispute, but psychiatry routinely downplays the risk, and insists that the benefits of these drugs outweigh any risks of actual violence that might exist.

There are two research studies that indicate a link between SSRI’s and violence, but both studies have limitations that make it difficult to draw firm conclusions.  The studies are:

Moore, TJ, Glenmullen, J, and Furberg, CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others.  This study, which was published in December 2010 in PLOS One, concluded:

“Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline [a quit-smoking aid], which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.” [Emphasis added]

Molero, Y, Lichtenstein, P, Zetterqvist, J, Hellner Gumpert, C, Fazel, S, Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study( 2015).  This study was published in September 2015 in PLOS One, and found:

“…there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19–1.73, p < 0.001, absolute risk = 3.0%).” [HR is Hazard Ratio]

In addition, there is also an enormous and growing body of anecdotal evidence (e.g. AntiDepAware) that these drugs are implicated in a great many acts of violence and suicide, particularly those in which individuals kill strangers and then take their own lives.

. . . . . . . . . . . . . . . .

Amazingly, psychiatry has consistently failed to conduct a comprehensive, prospective, formal research study on this matter, even though the need for such a study has been glaringly evident for almost 20 years.  It is very difficult to avoid the conclusion that psychiatry’s refusal to engage this question is motivated by a desire to suppress information, and to avoid the anti-psychiatry publicity that such a study will almost surely entail.

In this regard, it is noteworthy that in December 2012, shortly after the Sandy Hook shootings, a petition to order such a study was removed, with no explanation, from the White House petition site “We the People”, even though it was well on the way to obtaining the requisite number of signatures in the allotted timeframe.

Not only has pharma-psychiatry failed to conduct a formal study on this matter, they have also shamelessly and callously used these tragic incidents to further their own drug-pushing ends.  With each fresh incident, there are cries from  eminent psychiatrists and from various psychiatric bodies for more screenings, more “mental health treatment”, including enforced “treatment”.  These calls are heard even in cases where it is open knowledge that the perpetrator had been receiving psychiatric “treatment”, and had been taking psychiatric drugs.

Psychiatry’s self-serving exploitation of these incidents is not random or incidental, but is part of a tawdry marketing campaign outlined at a 1999 NAMI conference by DJ Jaffe, founder of Mental Illness Policy.org, and a founding member of the Treatment Advocacy Center.  Here are some quotes from his address as reported by MadNation:

“Laws change for a single reason, in reaction to highly publicized incidents of violence.”

“The media is gonna report on violence no matter what we want, and we have to… turn it to our advantage.”

And another quote from DJ Jaffe’s article “How to reduce both violence and stigma”, Newsletter of Staten Island AMI (SIAMI), December 1994:

“In addition, from a marketing perspective, it may be necessary to capitalize on the fear of violence to get the law [outpatient commitment legislation] passed.”

That psychiatry would pick up this theme and persistently seek to exculpate themselves, by stigmatizing their clients in this way, is a sad though unsurprising reflection.

. . . . . . . . . . . . . . . .

It is obvious that when this particular domino falls, it will be a major blow to psychiatry’s credibility, which is why they and their pharma allies have invested so much energy and resources into trying to keep the facts of this matter well under wraps.  And in this endeavor, their tentacles are spread far and wide.  Remember what Connecticut Assistant Attorney General, Patrick B. Kwanashie, said on August 22, 2013, during a freedom of information hearing on the Sandy Hook shooting.  In response to AbleChild’s request, he stated that releasing this information [about the psychiatric treatment of the shooter, Adam Lanza] could “… cause a lot of people to stop taking their medications.”  Why is the state of Connecticut so invested in young people continuing to take psychiatric drugs in the face of such strong indications of their implication in these horrendous incidents?  Why should the promotion of pharma-psychiatry’s deceptions become a part of a state government’s agenda?  Of course, the question is rhetorical.  Pharma distributes a great deal of largesse to politicians, and pharma always gets value for money spent.

. . . . . . . . . . . . . . . . . 

But the good news is that the petition to investigate the psychiatric drugs-violence link is back on We the People.  It went up on October 6, 2015, and has garnered 610 signatures as of today.  The goal is 100,000 signatures by November 5, 2015.  I strongly encourage all my American readers to add their signatures to this petition today.  And – if you feel comfortable doing so – please ask your friends/family/acquaintances to do the same.

Also, please consider writing to your political representatives, asking them to support this initiative.

There is an urgent need to investigate this matter thoroughly and transparently.  The one thing that venality and corruption cannot survive is the spotlight of truth.

 

Antidepressants:  Drugs, Not Medication

On April 7, John Read, PhD, a psychologist at Swinburne University of Technology in Melbourne, published a short article on Mad in America.  The title is:  Largest Survey of Antidepressants Finds High Rates of Adverse Emotional and Interpersonal Effects.  The article presents the results of a survey conducted in New Zealand and published online in February, 2014 in Psychiatry Research.  The survey involved 1,827 individuals who were taking antidepressants.  Dr. Read is widely published.  

Here are some quotes from the MIA article:

“Eight of the 20 adverse effects studied were reported by over half the participants; most frequently Sexual Difficulties (62%) and Feeling Emotionally Numb (60%).”

Note that more than half (60%) of respondents reported feeling “emotionally numb” as a result of taking antidepressants.  In a clinical trial, these people would probably be counted as treatment successes!

“Percentages for other effects included: Feeling Not Like Myself – 52%, Agitation 47%, Reduction In Positive Feelings – 42%, Caring Less About Others – 39%, Suicidality – 39%, and Feeling Aggressive – 28%.   If one had to imagine a combination of feelings most likely to increase the chances of a tragedy involving the loss of multiple lives it would be hard to do better than emotional numbing, agitation, aggression, suicidality and caring less about others.”

“It is worth mentioning that even a group of people who had accepted a biological treatment for their difficulties and had (mostly) found it helpful, did not unquestioningly swallow the ‘chemical imbalance’ theory of depression (and everything else) espoused by biological psychiatry and the drug industry.  The most strongly endorsed causes were:  Family stress (90.8% ‘agreed’ or ‘strongly agreed’), Relationship problems (89.9%), Loss of loved one (87.5%), Financial problems (86.9%), Isolation (86.3%),  and Abuse or neglect in childhood (85.4%), with Chemical imbalance (84.8%) coming in 7th, Heredity 12th, and Disorder of the brain 13th.”

“Finally, we gave participants ten possible reasons that prescription rates of antidepressants are so high (in 2013 the number of prescriptions in England – 53 million – surpassed the total population – 52.6 million). Among the more commonly endorsed  explanations were:  ‘Drug companies have successfully marketed their drugs’ (61%), ‘Drug companies have successfully promoted a medical illness view of depression’ (57%),  ‘GPs don’t have enough time to talk with patients’ (59%), and ‘Other types of treatments are not funded or are too expensive’ (56%). The least endorsed explanation for high prescribing rates was ‘Anti-depressants are the best treatment‘ (20%).”

 . . . . . . . . . . . . . . . .

The reality is that depression is not an illness, and antidepressants are not medication.  They are drugs that provide a transient feeling of well-being, or at least a feeling of numbness or “something different”.  They in no way address the root causes of depression, which are what they always have been:  the sad things that happen to us in our lives and/or a joyless, unfulfilling, treadmill-type of existence.

And it has long been my contention that in their “hearts”, both the psychiatrists and the recipients of these drugs know this.  The psychiatrists know that they are drug pushers, and the “patients” know that what they are getting is “a fix.”  And so the dance goes on.  The psychiatrists continue the pretense that they are real doctors; the “patients” settle for the fix; the APA invents the diagnoses; the psychopharma business booms; and the damage accumulates.

Psychiatry is not something good that needs some minor corrections.  Rather, it is something so fundamentally flawed and rotten as to be beyond redemption or compromise.  The blatant falsehood, that depression is an illness, has not only destroyed individuals, but eats at our personal and cultural resilience like a cancer.  It is time to put this lie to rest.  Please, if you’re not already doing so, speak out against this insult to human integrity and decency.

Antidepressant Drugs and Suicide Rates

In 2010, Acta Psychiatrica Scandinavica published a study by Göran Isacsson et al.  The paper was titled Antidepressant medication prevents suicide in depression.  Here’s the conclusion:

“The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.”

It’s a complicated article, with some tenuous logic, but note in particular the contrast between the fairly cautious wording in the conclusion, and the bold, even brazen, assertion in the title.

But, in any event, it’s all moot, because the article was retracted by the authors and by Acta Psychiatrica Scandinavica about sixteen months after publication.  The retraction had been requested by the authors because of “…unintentional errors in the analysis of the data…”

The research in question was conducted in Sweden.  Dr. Isacsson works at the Division of Psychiatry in the Karolinska Institutet, Stockholm.  He has been writing since at least 1994 on the putative efficacy of antidepressants in the prevention of suicide.

The 2012 retraction notice did not attract as much attention as the original article, but it did stimulate a measure of discussion.  Mickey Nardo wrote posts on the subject, here, here and here.  Bob Fiddaman wrote a post here, and Ivan Oransky of Retraction Watch wrote on the matter here.  Ivan reported that he had contacted Dr. Isacsson and Acta Psychiatrica Scandinavica for more information, and received the following reply from Dr. Isacsson:

“We discovered lately that there was a coding error regarding diagnoses in the database we utilized for the 2010 paper. When corrected, antidepressants were detected in depressed suicides as often as could be expected and not less than expected which was the crucial finding in the paper. This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.

The database has not been used for other studies so no other papers are affected.”

Jan Larsson, a Swedish journalist, wrote an interesting article on the matter.  Here’s an extended quote: 

“Isacsson’s findings from 2010 were widely published in Swedish newspapers, with headlines like  ‘Antidepressants prevent suicide’ (Dagens Nyheter), where it was said: ‘He [Isacsson] means that many become provoked to hear that depression is a deadly disease and that suicides can be prevented with medicines’. And, said Isacsson: ‘Therefore, it is important to show that antidepressants actually prevent suicide.’

In June 2012 I made an FOI request to Karolinska Institutet (where Isacsson is working) to get the corrected figures in this research project. I specifically wanted to get the document containing the correct percentage of antidepressants for those ‘who committed suicide and who had previously been treated at a psychiatric clinic for depression’ (the earlier mentioned group of 1077 persons).

The answer from Karolinska Institutet: This is confidential information, no data can be released.

It took a five month legal process to get access to the correct data. During this whole process Karolinska Institutet claimed that all the data in this research project were confidential.

In a final statement to the court, after having to answer specific questions, Karolinska Institutet stated that the correct figures did not exist at the time of the FOI-request – remember that they were said to be confidential at the time – but that the correct figures now had been produced.

Karolinska Institutet stated to the court: ‘that information has now been produced … The result shows that ‘the correct percentage’ is 56, meaning that of the persons who had been treated for depression in psychiatric care in the last five years before suicide, 56% had antidepressants in their blood when they committed suicide.’

So finally we got to know that the 15.2% in actual fact was 56% – an increase of 268% (from 164 persons to 603).

We had a seven pages long scientific article, with great impact in media, where doctors and the public got the message that antidepressants protect against suicide – an article built on Isacsson’s faulty finding that only 15.2% in the group had antidepressants in their blood when they committed suicide. And so the correct data, which completely defeated Isacsson’s speculations and conclusions in the original article, ‘published’ in a short statement to the court in Stockholm, where no doctor, no patient and no other researcher could find it.”

So, Dr. Isacsson et al’s original finding of 15.2% was a very large error indeed.  As I mentioned earlier, the logic underlying the study is tenuous, but Table 1 from the study will provide some insight into the authors’ thinking.

Isacsson Table 1

The controls (34,165) are people who did not commit suicide.  These are individuals who died from accidental and natural deaths.  Antidepressants were detected in 6.5% of these individuals post-mortem.

The suicides (18,922) represent all Swedish suicides from 1992 to 2003.  Antidepressants were detected in 22.4% of these people post-mortem.

Then the authors broke the numbers down further.  They note that 11,226 of the suicides had no psychiatric hospitalization in the 5 years prior to their deaths.  Of these individuals, 14.8% had antidepressants detected post-mortem.  The remaining 7,696 suicides, who had been in a psychiatric hospital in the preceding 5 years, had an antidepressant detection rate of 33.6%.

And this is where it gets complicated.  The researchers broke the hospitalized numbers down further, into:

  • Those hospitalized for depression only                              15.2%
  • Those hospitalized for other problems                               37.3%
  • Those hospitalized for depression plus other problems    33.2%

Their argument was that the first group (depression only) would be expected to have about the same, or an even higher, level of detected antidepressants as the other groups.  But, contrary to expectations, they found that they had the lowest level – about the same, in fact, as the group who had not been hospitalized in the previous five years.

So, they reason that large numbers of the hospitalized-for-depression-only group, most of whom presumably had antidepressants in their blood stream, had “been saved from committing suicide by antidepressant treatment.”

But as mentioned earlier, there was an error in the data, and the correct number was 56%.

Now all of this is well-known, but there is an aspect of the matter that has not, to my knowledge, been addressed previously.  Let’s go back to Dr. Isacsson’s letter to Retraction Watch.

“We discovered lately that there was a coding error regarding diagnoses in the database we utilized for the 2010 paper. When corrected, antidepressants were detected in depressed suicides as often as could be expected and not less than expected which was the crucial finding in the paper. This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.

The database has not been used for other studies so no other papers are affected.”

Dr. Isacsson is saying that antidepressants were detected in the depression-only suicides “as often as could be expected and not less than expected.”

Strictly speaking this is true.  56% is not less than 15%.  But the statement is also deceptive, in that 56% is a great deal more than 15%.  The difference in the study in question is 439 people.

Dr. Isacsson issued the above statement on March 19, 2012.  At that time, neither he nor Karolinska Institutet had released the 56% figure (on the patently spurious grounds of confidentiality).  It took several more months of legal process before the 56% figure was produced.  So at the time that Dr. Isacsson wrote  “…not less than expected…”, he probably did not anticipate that the true figure would ever be released.

But the plot thickens even further:

“This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.” [Emphasis added]

If a particularly low number (15%) warrants the conclusion in the article’s title (“Antidepressants medication prevents suicide in depression”), wouldn’t it be reasonable to infer that a particularly high number (56%) might warrant the opposite conclusion?  This is particularly so in that the increase from 15% to 56% can only have come at the expense of one or other of the remaining categories, which would make the discrepancy even larger.

I’m perfectly willing to accept that the original analysis was a genuine error.  But at the time of the retraction and the letter to Retraction Watch, Dr. Isacsson must have known that the true figure was 56%, and the question needs to be asked:  Why did he not release the 56% figure voluntarily at the time of discovery?  In addition, it is difficult to avoid the conclusion that his letter to Ivan Oransky was deliberately deceptive.  Mickey Nardo puts the matter well:

“It would be easy to drift into a debate about the relationship between suicide and antidepressants and miss the point here, which is that medical opinion should follow science, not the other way around. It’s clear that Göran Isacsson is of the opinion that antidepressants should be given to decrease the incidence of suicide – he has an absolute right to express that opinion. But when Isacsson offers as proof of his opinion a published study of the Swedish public records, and it turns out that his data either is wrong, not to be found, or never existed in the first place, we have to conclude that Göran Isacsson is an ideologue and has no place in the psychiatric literature.”

At the time of writing the article in question, Dr. Isacsson had financial ties to Lundbeck, Eli Lilly, and GSK.

INCIDENTALLY

Dr. Isacsson not only continues to promote the notion that wider use of antidepressant drugs will prevent suicides, but he also calls routinely for the removal of the FDA’s black box warning on this matter (e.g.  here).

In June 2010, the British Journal of Psychiatry published a debate on the topic:  The increased use of antidepressants has contributed to the worldwide reduction in suicide rates.  Arguing for the notion were Dr. Isacsson and Charles L. Rich, MD, Professor Emeritus of Psychiatry, University of South Alabama; arguing against were Jon Jureidini, MD, child psychiatrist at the Women’s and Children’s Hospital, Adelaide, and Melissa Raven, PhD, Research Fellow at Flinders University. Adelaide.

The debate effectively discredits Dr. Isacsson’s position, and is well worth reading.

Recurring Depression

This post was submitted by a reader.I am 46 years old and have taken antidepressants (Lexapro, Paxil, now Zoloft) for 10 years.  But the reason I began taking them wasn’t due to my own need for relief from depression or anxiety.  It was actually an effort to improve my relationship with my husband at the time.  He suffered from depression and took medication, but said that I was overly critical, driven, intense, etc. and I think he was right.  But I was also young and immature, and am an engineer by profession.  I do have a critical thought process, no doubt.  We were mismatched from the start and separated not long after I started the medication, but have a 11 year old son together.  The divorce process, and going back to work full time as a single mom was difficult and stressful.  But after taking the Lexapro for over 4 years, I actaully began feeling lethargic and depressed and decided to stop taking it cold turkey.  Big mistake, I learned the hard way, and ended up on Paxil after a few months. Now I am having the same problem with the Paxil, and I really just want to get off the medication all together because I feel that it is causing the depression.  I was never depressed to begin with, but now I am!  After a couple of bad experiences with withdrawal symptoms from coming off the meds, I am really apprehensive about trying to taper off of them, but I want myself back, not this medicated, lethargic, irritable, unproductive person.  I was far from perfect, as my ex-husband made painfully clear, but I always had hope for a better future and energy to work for it.  I can’t help but feel that the meds have done more harm than good in my particular situation.  I just wonder if others have had similar experiences?  Thank you and best wishes in whatever you are searching for…

A Reader

Exploiting the Placebo Effect:  Legitimate Practice or Chicanery?

On June 13, 2014, Psychiatric Times published an article by Steve Balt, MD.  The article is titled Assessing and Enhancing the Effectiveness of Antidepressants, and is a good deal more candid as to the efficacy of antidepressants than one normally encounters from psychiatry.  Dr. Balt is a private practice psychiatrist in California.  He is the editor-in-chief of The Carlat Psychiatry Report.

The article opens with the observation that despite the large number of antidepressants on the market, and decades of clinical experience, no particular product seems to have emerged as substantially better than the rest.

“As a result, most psychiatrists choose antidepressants not on the basis of efficacy, but rather on the basis of insurance coverage, adverse-effect profiles, or particular clinical features of depression (eg, melancholic, atypical, anxious features), for which some differences in efficacy do exist.”

The author refers to a number of studies, including NIMH’s STAR*D trial, and states:

“Despite the scope and initial aims of the study, no single antidepressant strategy or combination appeared more advantageous than any other.”

And:

“Effectiveness trials, therefore, seem to confirm the conventional wisdom that no single antidepressant works better than—or worse than—any other.”

And:

“Findings indicate that there were no significant differences in effectiveness of antidepressants, although individual drugs did differ in terms of onset of action and ease of dosing.”

In studies that did detect differences between products, Dr. Balt expresses the view that they “…were slight and of questionable clinical significance.”

Then the author makes this surprisingly candid observation:

“Because a meta-analysis is only as good as the data on which it is based, these meta-analyses must be considered in light of the very real problem of selective publication. This is the tendency for favorable results to be published, while negative or neutral results are not. In an analysis of 74 antidepressant trials registered with the FDA between 1987 and 2004, Turner and colleagues found that nearly half (36, or 48.6%) were negative, and the vast majority of these were either not published or were published in a way that made the drug seem favorable. Likewise, industry-sponsored studies are more likely to favor the manufacturer’s drug, often because of nuances in experimental design. While most researchers make every effort to include unpublished results in their meta-analyses, the “file-drawer” phenomenon of unpublished negative results may bias the conclusions of analyses that exclude the inaccessible data.”

Dr. Balt summarizes all of this with what he calls:  two “stark truths about antidepressants.”

“First, there seem to be no significant differences among them; although future research may uncover patient-specific biomarkers that favor one medication over another, none has yet done so. Second, and somewhat surprisingly, antidepressant effectiveness is quite low.”

And he concludes:

“Thus, in the absence of data that can predict the best antidepressant regimen for a patient, enhancing the effectiveness of an antidepressant seems to be the best strategy.”

Dr. Balt mentions two possible strategies for enhancing the effectiveness of an antidepressant.  The first is to recognize that depression is not a single condition, but rather  “…multiple conditions, each deserving of its own unique treatment approach.”  He states that  “…much of the antidepressant response in mild to moderate depression may be due to the placebo effect”, and that anxious individuals may do better with psychotherapy.

Dr. Balt’s second suggestion for effectiveness-enhancing might be to combine antidepressants, or to supplement them, with what he calls “augmentation agents”.  But he acknowledges that while there might be some “intuitive appeal” to these strategies, there is little in the way of supporting evidence for their effectiveness.

Then:

“The more important question may be more about whom we are treating rather than what we treat with.”

Which, of course, is close to what we, on this side of the debate, have been saying all along – that effective help must be tailor-made to the personal characteristics and context of the individual, and that the facile labels which psychiatrists optimistically and misleadingly call “diagnoses” are counterproductive.

For the sake of thoroughness, Dr. Balt dismisses the relevance of genetics:

“In reality, however, the genetic contribution likely involves an impractically large number of variants, each having a very small effect, that together contribute to the very complex phenotype of antidepressant response. Indeed, 2 meta-analyses, using genome-wide analysis to identify polymorphisms to predict treatment response, found only a 1.2% contribution or no contribution at all.”

And metabolism:

“With few possible exceptions, no evidence exists that blood concentrations influence antidepressant outcomes, and there are multiple nongenetic factors that influence drug metabolism, such as diet, other medications, and adherence.”

This last assertion – that antidepressant blood concentrations have no effect on outcome – is a truly extraordinary admission from a psychiatrist, and could even be interpreted as the (psychiatric) baby going out with the bathwater.

But then, just as Dr. Balt appears to be morphing into a psychotherapist, he slips back into psychiatric mode:

“Not surprisingly, we can take advantage of patient preferences to enhance treatment outcomes.” [From the context, it is clear that he means drug treatment]

“…the quality of the therapeutic alliance between prescriber and patient is sometimes a better predictor of patient outcome than which drugs are prescribed.”

The last quote sounds positive, but watch where Dr. Balt goes with it:

“One study found that ‘effective’ prescribers obtained better outcomes with placebos than ‘less effective’ prescribers with active antidepressants.  Asking ‘which’ medication may be less important than the ‘meaning’ of medication to both clinician and patient.”

So what Dr. Balt is describing and suggesting is to use the therapeutic alliance, not to connect to the individual, and to provide real support in the resolution of personal concerns and problems.  But rather, to enhance the effectiveness of psychiatric drugs.

“The recent emphasis on personalized antidepressant prescribing seems warranted, but rather than taking a combination or pharmacogenomic approach to medication selection, clinicians should focus more on a personalized approach, establish realistic (but hopeful) expectations, and use patient preferences and beliefs to optimize outcomes.” [Emphasis added]

And:

“Even when patients’ preferences do not have any bearing on outcome, matching treatments with patients’ preferences increases their willingness to initiate and adhere to a treatment plan.” [Emphasis added]

So if a client believes that Zoloft, say, will be helpful, because it seemed to help a family member, perhaps, or even because the TV ad made the product seem attractive, the psychiatrist should prescribe Zoloft?  That feels a little bit like a con.  It’s an admission that although the drugs aren’t much good, we can sort of trick the client into enrolling, adhering, and perhaps even becoming happier.

And why is “adherence” so important, if the drugs aren’t much use to begin with, and often bring a host of additional problems?

I can appreciate Dr. Balt’s honesty concerning antidepressants, but, in my view, his recommendations entail a good measure of condescension and disrespect.  They also have the potential to encourage increased prescribing of drugs, despite his assertions of their limited efficacy.

. . . . . . . . . . . . . . . .

And incidentally, besides his recent critique of antidepressants, Dr. Balt had earlier gone on the record with some biting and revealing criticism of a psychiatric clinic where he worked from about 2009 to 2012.

In August 2014, Dr. Balt was taken to task on Twitter for being a top prescriber of Seroquel (quetiapine), a neuroleptic, in California in 2009 (1,000+ prescriptions).  In a subsequent interview with William Heisel of William Heisel’s Antidote, Dr. Balt is quoted as writing:

“More than 1,000 new prescriptions in one year is hard to fathom. Given my part-time schedule there, it would have meant six to seven new prescriptions each day, which is impossible. However, if it includes each month’s refills for patients who took the drug all year long, that does not seem at all unreasonable for that clinic. Given the volume of patients (and their specific requests for Seroquel, a medication in high demand), automatic refills were frequently given.”

And:

“That was my first full year at a clinic where quick visits, busy schedules, and knee-jerk prescribing were the order of the day. Over time, I became quite disappointed — if not angry — at what seemed to pass for ‘treatment’ and the overwhelming emphasis (on the part of patients and doctors alike) on the use of psychotropics to manage what were, most of the time, sociocultural stressors in our largely indigent, population.”

And:

“I’d estimate that 50% to 70% were for ‘schizophrenia.’  Keep in mind, however, that a schizophrenia diagnosis is freely given in these settings, e.g., for otherwise healthy people who say, ‘I talk to myself sometimes,’ or ‘I sometimes see shadows at night,’ or ‘I’m always looking behind my back when I’m outside,’ etc.  As for the rest, those prescriptions were probably given for bipolar disorder or off-label for sleep.  As I learned more about the metabolic effects of Seroquel I tried to use less of it.”

And:

“I have worked at other clinics, and my experience tells me that overprescribing is rampant in the Medicaid setting and apparently accepted as the standard of care. I have seen the same over-reliance on psychotropics, over-diagnosis and waste of resources in other parts of the state, although the volumes were not nearly as high as what I experienced in Oakland.”

So Dr. Balt is describing a psychiatric practice in which:

  • “automatic” refills for a neuroleptic were frequently given
  • “knee-jerk prescribing” was the order of the day
  • psychosocial stressors were “managed” with psychotropic drugs
  • diagnoses of schizophrenia were “freely given”
  • and overprescribing for Medicaid recipients (i.e. poor people) was “rampant”

Dr. Balt is now in private practice, and on his Psychology Today bio page he tells us that he offers “both medication management and psychotherapy” and that his “…approach to medications is a conservative one.”

And then he writes:  “… I am willing to help patients taper or discontinue medications that provide little benefit, or which cause harm.”  I have no reason to doubt Dr. Balt’s sincerity in this matter, but the fact that he felt the need to issue such a statement implies, I think, that it is not standard practice in psychiatry.  In other words:  psychiatrists routinely leave people on  “…medications that provide little benefit, or which cause harm.”  This, of course, is something that we on this side of the debate have been saying all along, but it is interesting to see these ideas coming from within psychiatry itself.