MetaFilter posts tagged with Antidepressants

Psychotropic medication efficacy and publication bias

OmieWise — Tue, 03 Apr 2012 05:47:55 -0800

Antipsychotics: "The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently."
Antidepressants: "We found a bias toward the publication of positive results. Not only were positive results more likely to be published, but studies that were not positive, in our opinion, were often published in a way that conveyed a positive outcome. [...] Using both approaches, we found that the efficacy of this drug class is less than would be gleaned from an examination of the published literature alone. According to the published literature, the results of nearly all of the trials of antidepressants were positive. In contrast, FDA analysis of the trial data showed that roughly half of the trials had positive results." Previously Previous news about antipsychotic efficacy from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study.

Falling STAR*D?

Keter — Sat, 14 Jan 2012 12:16:06 -0800

Falling STAR*D?: It is common practice for psychiatrists to switch depressive patients between different antidepressants if their current drug does not evince a symptomatic response. Despite clinical wisdom supporting this, little empirical, controlled evidence exists to direct “switching” protocols (e.g. if a patient with Z characteristics is on drug X, is it usually better to switch to drug A, B, or C? Will switching help at all?) in the psychopharmacological treatment of depression. The NIMH-funded STAR*D (Sequenced Alternatives to Relieve Depression) study aimed to address these questions of treatment direction in a very large (n>4000), “real-world” sample using a multi-phase treatment plan with different drugs (and cognitive therapy) at every step to maximize chances of eventual remission. Overall, the NIMH reported that about 67% of patients eventually achieved remission, with few differences in effectiveness between different types of treatment at each step. However, researchers and commentators have raised concerns regarding inconsistent reporting of outcomes, after-the-fact changes in study design and analysis, and other issues that may have inflated, partially invalidated, or misrepresented widely reported treatment outcomes. These inequities may also have implications for the secondary moderator analyses (i.e. does trait A predict switching to X or Y is better?) that were a major reason for the study. Criticisms of STAR*D include (but are not limited to): * Switching primary outcome at the study's conclusion from the widely used (for better or for worse) Hamilton Rating Scale for Depression to the Quick Inventory of Depressive Symptomatology, ostensibly due to high patient dropout preventing acquisition of HRSD assessments (though robust statistical methods for imputing/estimating missing data in this sort of study exist). While the HRSD was performed by blinded assessors independent of the immediate treatment situation, the QIDS-SR was actually taken as part of the treatment-guiding process, leading to conjecture that there was more demand on patients to respond positively to the QIDS-SR versus the HRSD. (There is some odd confusion over whether the QIDS-SR was administered in-person as the study protocol would indicate, or over a computerized telephone check-up system.) Notably, the QIDS-SR reported higher rates of remission than the HRSD. However, some articles on individual steps of treatment did report on HRSD outcomes. * A large number of patients (607) entered treatment at milder levels of depression than the minimum set by study protocols (i.e. with HRSD scores less than 14, with remission defined as HRSD less than 7), but were treated and included in the summary findings of the study. Previous research has suggested that milder depression may respond somewhat similarly to placebo or antidepressant treatment. * Lack of placebo control leading to diminished ability to conclude to what degree apparent remission at each step is spontaneous or treatment-driven (i.e. if you remit at step 2, is it because of the new drug or because depression can spontaneously remit, especially for more moderate depressions). * Considering success-trending dropouts in many cases as treatment successes despite front-end guidelines to the contrary for some types of dropout, to the result of raising treatment success rates. (Though Pigott and critics often take the reverse interpretation 100%, equating dropout always with lack of clinical efficacy, which may be overly biased in the other direction.) Dropouts in the study over the course of follow-up, though always expected, were astonishingly frequent in STAR*D (perhaps as high as around 90%). * Confusion over different STAR*D papers publishing different rates of suicidality for the Celexa step of the study (each using slightly different sampling from the STAR*D cohort), some an order of magnitude higher than others. The higher rates were reported in a paper examining a particular gene variant’s ability to predict suicidality on the drug, which was associated with a patent for screening this gene variant. * Lack of publication on several pre-established secondary outcome measures (e.g. general assessment of functioning, work productivity) several years after the study finished leading to suspicions regarding treatment failure. At least one STAR*D investigator may agree with some of these criticisms, Dr. Maurizio Fava (see remarks at end). Dr. Fava, while not at all dismissive of the helpful role of psychopharmacology in psychiatry (rather the contrary), has in the past raised concerns regarding lack of research on the efficacy and side-effects of long-term antidepressant use [paywalled, summarized partially here]. Medical journalist and psychotropic drug critic Robert Whitaker (previously) has also blogged his criticisms regarding STAR*D, largely based on the findings of Dr. Pigott’s group above. A large number of papers have been published examining data from the STAR*D study (bibliography incompletely updated), many exploring the differential contribution of genetic profiles to antidepressant response, to varying degrees of success. And it would be incorrect to say STAR*D got everything wrong: for example, one unique and praised feature of the STAR*D trial over other clinical trials, as noted by Neuroskeptic, is the inclusion of patients who have co-morbidities and depressive features that may exclude them from more traditional clinical trials. These more complexly symptomatic patients may be representative of depression within real-world populations compared to patients found in antidepressant trials. Analyses of the STAR*D data suggest that “clinical trial” patients (who composed a minority of the STAR*D cohort) responded significantly better to treatment than other patients. The investigators of STAR*D themselves conjectured from this result that standard clinical trials may overestimate the effects of antidepressants.

Placebos

homunculus — Tue, 25 Aug 2009 09:08:59 -0800

Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

Coming of Age on Antidepressants

homunculus — Wed, 16 Apr 2008 14:15:00 -0800

Who Are We? Coming of Age on Antidepressants. [Via Mind Hacks.] The Medicated Americans: Antidepressant Prescriptions on the Rise.

Anti-depressants, Serotonin and Depression

OmieWise — Thu, 17 Jan 2008 08:12:07 -0800

"Researchers found that failing to publish negative findings inflated the reported effectiveness of all 12 of the antidepressants studied." See also: Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. NEJM paper referenced. (Subscription required) Older: Antidepressants Versus Placebos: Meaningful Advantages Are Lacking,
but, Small Effects Are Not Trivial From a Public Health Perspective.

Seven Interview with Foster Children

chunking express — Sat, 29 Dec 2007 08:29:32 -0800

I took my video camera to a Foster Care Alumni meeting and asked seven foster kids to tell me about there experiences in Child Protective Services while wards of the state: Tristen, Andrew, Kyle, Aisha, Elnita, Ashley, Joshua. The author of the video is interested in how these children were drugged from a young age, but they each talk about their experiences in general, which usually aren't that great. I thought Tristen's video was particularly depressing.

Ricky Williams on 'Oprah'

hydatius — Wed, 21 Nov 2007 10:11:39 -0800

Talking back to Prozac. Review article in The New York Review of Books, covering some issues concerning the diagnosis and treatment of depression.

Anti-depressants increase suicide risk in young adults, FDA warns

shivohum — Tue, 12 Dec 2006 15:08:09 -0800

Anti-depressants increase suicide risk in young adults, FDA warns. "When results are analyzed by age, it becomes clear that there is an elevated risk for suicidality and suicidal behavior among adults younger than 25 years of age that approaches that seen in the pediatric population." More here and here. This follows the FDA finding that anti-depressants increased the risk of suicide in young children. The FDA now requires manufacturers of anti-depressants to include warnings, and plans to meet on Dec 13 to discuss the findings further.

Zoloft Found Safe, Effective in Children

Wicker — Tue, 26 Aug 2003 14:42:59 -0800

Zoloft Found Safe, Effective in Children The study was funded by Pfizer Inc., which makes Zoloft. Visit The International Coalition For Drug Awareness to find out what SSRI Meds can really do to your kids...

And they work how exactly?

grahamwell — Sat, 09 Aug 2003 13:12:43 -0800

Anxious? Depressed? - you need more brain cells. Just take one of these twice a day. New research shows that antidepressants may not work as we thought at all, rather they actually stimulate growth of cells in the hippocampus area of the brain. This may all be for the good - but it seems strange that we release millions of happy pills and market them as safe without knowing for sure what they do. Perhaps its the money talking.

Hmm. Why am I not surprised?

Ezrael — Tue, 06 Jun 2000 19:05:13 -0800

Hmm. Why am I not surprised? Muddling with your serotonin in such a drastic way has always struck me as an overreaction to depression. Let's be honest. In a world jam-packed with aggressive apes who deny that they are apes, a little depression is a healthy response. Taking a serotonin re-uptake inhibitor just because you feel blue is like taking 10000 micrograms of Acid because you like the Harry Potter books.

Speaking of Prozac...

SuperGoat — Wed, 22 Mar 2000 09:20:50 -0800

Speaking of Prozac... Did Prozac and Ritalin cause the Columbine disaster? Are these drugs causing kids to kill? The people of "A White Rose" seem to think so. You be the judge.