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For Those Still Convinced Antidepressants Have Non-Placebo Value

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Even though meta-analyses of antidepressant studies have repeatedly shown that antidepressants’ effects are barely distinguishable from placebo, many opponents of suicide rights still point to meds as a proper course of action for those who wish to die. Those unlucky enough to be hospitalized after a suicide attempt (like me) are still administered antidepressants in hospital – by force, if necessary.

Anyone who still thinks antidepressants have non-placebo value should listen to this 20-minute interview with Dr. Irving Kirsch, the lead investigator on the major meta-analyses of antidepressant drugs.

Major points:

  1. The serotonin hypothesis is “dead in the water.” Studies have repeatedly failed to demonstrate that serotonin deficiency is responsible for depression.
  2. The effects of antidepressants are indistinguishable from placebo, especially when data is included from studies that have not been published because they did not get a positive result. (Dr. Kirsch and others obtained these unpublished studies using the Freedom of Information Act.) Both the publication bias in general, and specific monetary incentives, are implicated.
  3. Antidepressants’ “effects” are independent of the drug mechanism. Antidepressants that work on inhibiting serotonin reuptake have the same effect as antidepressants that work on other neurotransmitters or even other chemicals; that is, their effect is indistinguishable from placebo.
  4. Antidepressant “effects” are independent of dosage.
  5. SSRIs (selective serotonin reuptake inhibitors) show the same level of response as SSREs (selective serotonin reuptake enhancers) – that is, drugs with the opposite mechanism show the same result!
  6. Contrary to my previous suppositions, the antidepressants’ effects are dismal regardless of the severity of depression. Severely depressed patients (who make up most of the study groups!) are not significantly more likely to respond to antidepressants than less severely depressed individuals.

As Dr. Kirsch puts it, “that’s what I call a placebo.”

The next time you see someone recommend drugs as a course of therapy for depression, please point them here, or to the podcast.

Meanwhile, the only drug that consistently cures depression in laboratory studies is only available on the black market.


(In the interests of full disclosure, I take one of these yummy placebos every day – citalopram. Similarly, millions of people feel better every day by using quack therapies such as chiropractic, homeopathy, and prayer. The folks making money off those therapies feel even better.)

Written by Sister Y

March 7, 2011 at 6:12 pm

What the DSM-II Got Right

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The DSM-II, or Diagnostic and Statistical Manual of Mental Disorders, Second Revision, was the diagnostic guide specifying the criteria for psychiatric disorders between 1968 and 1980.

In general, the DSM-II is very suspect. Until 1974, the DSM-II famously listed homosexuality as a mental disorder – specifically, it was listed under Personality Disorders and Certain Other Non-Psychotic Mental Disorders, Sexual Deviations, as DSM-II 302.0, Homosexuality. (Certain wacky Christian fringe groups and many Catholics still think the removal of homosexuality from the DSM was a real shame.) The DSM-II uses quaint terms like “neurosis” and includes controversial diagnoses like “Psychosis with childbirth,” “Involutional melancholia,” and “Depersonalization syndrome.”

More recent revisions of the DSM (DSM-III, DSM-IV, and DSM-IV-TR) are generally considered to contain diagnoses that map more scientifically onto observable real-world phenomena.

Partially due to a realization of ignorance of the etiology of many diseases, revisions beginning with the DSM-III tended to erase etiology from the names and diagnostic criteria of many conditions (except conditions where the etiology is obviously central, such as 292.1, “Psychosis with other syphilis of central nervous system” (psychosis caused by syphilis).

Unfortunately, the refusal to link mental diseases with etiology resulted in a step backwards in the diagnosis and treatment of depression, according to Professor Gordon Parker (“Is depression overdiagnosed? Yes,” British Medical Journal 2007:328).

“Fifty years ago [under DSM-II criteria],” says Professor Parker, “clinical depression was either endogenous (melancholic) or reactive (neurotic). Endogenous depression was a categorical biological condition with a low lifetime prevalence (1-2%). By contrast, reactive depression was exogenous – induced by stressful events affecting a vulnerable personality.” In other words, the DSM-II recognized a type of biologically-determined depression, with a population frequency similar to other major, debilitating psychiatric disorders such as schizophrenia. (In fact, for various reasons including the severity and similar lifetime prevalence as schizophrenia, my reading of this is that endogenous “melancholic” depression, if studied in more detail, would be found to be specifically genetically linked, just like schizophrenia.) Another type of depression, much less severe and much more common, resulted from people “becoming depressed” secondary to negative life events.

Then, in 1980, the DSM-III revisions changed all that. They created a new taxonomy of depression, and rather than exogenous and endogenous, began to classify depression as “major” or “minor,” with no reference to etiology. Only the diagnostic modifier “melancholic features,” which I’ve previously discussed in my essay “Depression, Cognition, and Value,” was left of the endogenous depression distinction.

Unfortunately, the major/minor classification has never been borne out by scientific studies (though the “melancholic features” modifier is scientifically robust). As Professor Parker points out,

Meta-analyses show striking gradients favouring antidepressant drugs over placebo for melancholic depression. Yet trials in major depression show minimal differences between antidepressant drugs, evidence based psychotherapies, and placebo. . . . Extrapolating management of the more severe biological conditions to minor symptom states reflects marketing prowess rather than evidence. Depression will remain a non-specific “catch-all” diagnosis until common sense prevails. [Emphasis mine; citations omitted.]

Scientific studies do not back up diagnoses of “major” and “minor” depressive disorders as true disorders. The DSM-III criteria for major depression has “failed to demonstrate any coherent pattern of neurobiological changes or any specific pattern of treatment response outside in-patient treatment settings,” says Professor Parker. In other words, while the quaint diagnosis of “melancholic depression” under the DSM-II retains some scientific validity, the diagnosis of Major Depressive Disorder under the DSM-IV is not scientifically valid in any of the normal senses.

The implications for suicide rights are several. First, to the extent that everyone who is suicidal is assumed to be suffering from “Major Depressive Disorder,” we are being diagnosed with a disease whose scientific validity is extremely questionable. The laughable overdiagnosis of “Major Depressive Disorder,” coupled with the diagnosis’ failure to “demonstrate any coherent pattern of neurobiological changes or any specific pattern of treatment response,” must shake our confidence in the fashionable hypothesis that all suicide is secondary to a genuine mental disorder. Second, to the extent that our psychiatric establishment chooses to use these diagnostic criteria (Major Depressive Disorder), and since meta-studies generally show little significant difference between antidepressant medications, “evidence-based psychotherapies,” and placebo, if we have depression, we must be said to have an incurable disease. Both citizens in general the those in medical professions should be much more circumspect about their willingness to force people with “Major Depressive Disorder” to remain alive against their will, and especially to forcibly medicate or “treat” this “disease.”

While I think endogenous depression is a “real” disease, unlike DSM-IV Major Depressive Disorder, I do not think that all suicides have endogenous depression – not even close – nor do I think that endogenous depression is always treatable. At best, it is marginally more treatable than DSM-IV Major Depressive Disorder – that is to say, not very. The famous study that found that SSRIs work no better than a placebo found a slightly significant difference between drug and placebo for the most severely depressed people, which could be tracking endogenous depression, but this was primarily due to that group’s much lower response to placebo. From the study:

Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. . . . Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

Written by Sister Y

August 1, 2008 at 10:31 pm

Suicide Trends: Antidepressants, They Do Nothing

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Suicide trends in the United States: this is what they look like, in case you’re confused.

One question often asked, in reference to whether antidepressants are effective, is whether suicide rates have declined in response to widespread antidepressant use. Many authors have attempted to answer this question. One study attempted to demonstrate a time correlation between antidepressant use and declining suicides. Why did these authors cut off the data for the 1950s, and begin their analysis with data for the 1960s? Including the suicide rate data (very low, especially among women) for the 1950s would reduce confidence in the authors’ conclusion that antidepressant use is time-correlated with a drop in suicides. (The 1950 data occurred long before SSRIs were available, but undercut the authors’ claim that the 1960-1988 data represented the baseline condition from which suicide rates dropped.)

More importantly, given the data that antidepressant use is not associated with a drop in suicidal behavior, such as suicidal ideation and suicide attempts, even if time correlation were properly demonstrated, the effectiveness of antidepressants is not supported. It is difficult to imagine any way in which antidepressant medications could reduce suicides while having no effect on suicidal ideation, behavior, and attempts, especially given that the JAMA study found that “cry for help” insincere suicide gestures decreased slightly between the 1990-1992 and 2001-2003 studies.

Actually, there is a way that antidepressants could reduce completed suicides but not suicidal behavior or ideation: if they interfere with cognitive ability in general, rendering suicides clumsier or more poorly planned.

But the more likely explanation, given all the data, including the February study that the commonly prescribed antidepressants don’t work better than placebo, is that some factor other than antidepressant use is responsible for any drop in suicides. The obvious answer is that, to the extent that there has been a drop in suicide rates, it’s due to the drop in gun ownership over the past few decades. (Here’s a graphic.) As I have previously noted, gun ownership is highly correlated with suicide. Reduction in gun ownership, in addition to reduction in availability of other reliably lethal methods of suicide, such as lethal pesticides (frequently used for suicide by men and women in poor countries) and barbiturate sleeping pills, is much more likely to be responsible for the drop in suicides than increased antidepressant use. These factors – what might be termed coercive suicide prevention methods – would easily explain a drop in suicide not associated with a drop in suicidal ideation or behavior.

Thanks to Overcoming Bias poster Peter McCluskey for the pointer to the PLoS article.

Edit: Cognitive behavioral therapy (CBT), much hyped for depression, apparently doesn’t work either. From the study:

Stravynski and Greenberg suggested that all models of psychotherapy, including cognitive behavior therapy, may be “equally unsound scientifically but they energize the therapists and provide useful fictions to activate the patients to lead somewhat more satisfactory lives.” [Citations omitted.]

Written by Sister Y

June 12, 2008 at 11:30 pm