Mental Health Blogs

This is one of the oddest studies I’ve seen in a while. It was published in the American Journal of Psychiatry earlier this month and it’s literally an example of trying to pull the wool over the public’s eyes concerning the efficacy of atypical antipsychotics used to augment an anti-depressant in the treatment of major depression. The study authors are J. Craig Nelson of UCSF and George Papakostas of Harvard/Mass General. Their stated purpose was:

“The authors sought to determine by meta-analysis the efficacy and tolerability of adjunctive atypical antipsychotic agents in major depressive disorder.trial, depression scale used, response and remission rates, and discontinuation rates for any reason or for adverse events.”

They then focused on published studies or studies presented as posters at various conferences for the use of Zyprexa, Risperdal, Seroquel and Abilify as augmentation treatments. Oddly, only Abilify is approved for such use by the FDA. Seroquel’s maker, AstraZeneca, is still awaiting FDA approval of its drug as an augmentation–and has been waiting for almost six months since an FDA panel recommended–quite gingerly–that the agency approve the drug. That’s an unusually long wait and tells you that something odd is afoot.

Anyway, the researchers didn’t report in their paper the efficacy of the four drugs. Instead, they pulled an odd trick and reported the odds ratio of all the studies of the four drugs as depression augmenters to placebo. In other words, they were telling readers the chance that this class of drugs beat placebo–not the efficacy of the drugs (except in a slippery manner I’ll come to). That strikes me as a consumer and science dork as an utterly useless measure with little real world clinical significance, especially since several of the 16 studies were of only four weeks duration–some of the shortest depression treatment studies I’ve ever heard of.

They reported the odds of beating placebo as:

“Adjunctive atypical antipsychotics were significantly more effective than placebo (response: odds ratio=1.69, 95% CI=1.46–1.95, z=7.00, N=16, p<0.00001; remission: odds ratio=2.00, 95% CI=1.69–
2.37, z=8.03, N=16, p<0.00001). Mean odds ratios did not differ among the atypical agents and were not affected by trial duration or method of establishing treatment resistance. Discontinuation rates for adverse events were higher for atypical agents than for placebo (odds ratio=3.91, 95% CI=2.68–5.72, z=7.05, N=15, p<0.00001)."

Translation: atypicals as augmenters are 69 percent more likely to produce a response than is placebo and 100 percent more likely to produce remission than is placebo. Sounds awesome, right?

Now, here’s why you should be very suspicious of the apparent epic victory over placebo:

“The odds ratio for remission was 2.00, with a number needed to treat of nine.”

The NNT as it’s known means the number of people who would have to try a treatment before one person would realize a treatment benefit. An NNT of nine people translates to an overall efficacy for atypical augmenters of about 11 percent. Staggeringly low. And hardly the victory researchers seemed to be claiming.

So why would such august researchers report an odds ratio that favored the drugs instead of reporting their individual and pooled lack of efficacy? I have no idea, but here are there conflicts of interest declarations from the paper:

“Dr. Nelson has received grant support from or served as a speaker on advisory boards, or as a consultant for Abbott Laboratories, Acadia Pharmaceuticals, AstraZeneca [maker of Seroquel], Biovail, Bristol-Myers Squibb [maker of Abilify], Corcept, Cyberonics, Eli Lilly [maker of Zyprexa], Forest Pharmaceuticals, GlaxoSmithKline, Health Resources and Services Administration, Janssen Pharmaceutica [maker of Risperdal], Medtronics, Merck, NIMH, Novartis Pharmaceuticals, Organon, Orexigen, Otsuka [creator of Abilify], Pfizer U.S. Pharmaceuticals Group, Sepracor, Shire, and Sierra Neuropharmaceuticals. Dr. Papakostas has received grant support from or served as a speaker, on advisory boards, or as a consultant for Bristol-Myers Squibb [maker of Abilify], Eli Lilly [maker of Zyprexa], Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, NIMH, Otsuka [creator of Abilify], PAMLAB LLC, Pfizer U.S. Pharmaceuticals Group, Pierre Fabre Laboratories, Precision Human Biolaboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth.

“No external funding was received for the study design, trial search,
data analysis, interpretation of the data, writing of the paper, or the
decision to submit for publication.”

When you’ve had recent research and consultant funding from the companies making the drugs is it any wonder that study resulted are measured in such a fashion that they sound totally wonderful when they are not? I’m just asking.

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Related posts:

1. Suspicious Antipsychotics For Depression Study Comes Into Question
2. Yet Another Study Links Processed Food To Depression
3. Placebo Outperforms Seroquel In Teen Bipolar Depression Study
4. JAMA Study Slaughters Antipsychotics For Kids, Teens Paradigm
5. Study, BBC Claim Anti-Depressants Work Instantly, 6 Reasons To Be Skeptical