Antidepressants: An Emperor with No Clothes?

On rare occasion, I have reported startling findings that challenge current wisdom: Brain training games do NOT boost intelligence. Traumatic experiences are NOT often repressed. Seasonal affective disorder (wintertime blues) is NOT widespread.

The just-arrived lectures from the 2016 Bial Symposium on Placebo Effects, Healing and Meditation, offers another shocker: In an update on his meta-analyses, Irving Kirsch concludes that antidepressant drug effects are close to nil.

Here’s Kirsch’s gist: Many, many studies, including unpublished drug trials made available by the FDA, consistently show that

1. Antidepressants work. They produce clinically significant benefits (using a standard depression scale).
2. Placebos work, too. In two large meta-analyses, placebos produced 82 percent of the antidepressant effect. Moreover, “the difference between drug and placebo is . . . so small that clinicians cannot detect it.”
3. Side effects can “unblind” a drug. The statistically (but not clinically) detectable drug effect may be attributable to antidepressants’ detectable side effects.
4. The FDA only counts “successful trials.” Kirsch reports that despite meager evidence of antidepressant efficacy, the drugs gain approval because of a stunning FDA policy—which ignores trials that find no drug effect and reports only successful trials.
5. “All antidepressant drugs seem to be equally effective.” As one would expect from a placebo effect, the benefits of various antidepressant drugs are “exactly the same regardless of type of drug.” Various serotonin-increasing drugs relieve depression, but so does a drug that decreases serotonin! “What do you call pills, the effects of which are independent of their chemical composition?,” asks Kirsch. “I call them ‘placebos.’”

Given that antidepressants work, even if they are hardly more than active placebos, what’s a clinician to recommend? Kirsch notes three considerations:

1. Antidepressants have side effects, which can include sexual dysfunction, weight gain, insomnia, and diarrhea.
2. Antidepressant use increases the risk of relapse after recovery.
3. Cognitive behavioral therapy, acupuncture, and physical exercise also effectively treat depression.

Ergo, “When different treatments are equally effective, choice should be based on risk and harm, and of all of these treatments, antidepressant drugs are the riskiest and most harmful. If they are to be used at all, it should be as a last resort.”

But surely this is not the last word. Stay tuned for more findings and debate.