The Antidepressants Debate

In this 2014 Lancet comment, Peter Gøtzsche responds to David Nutt et al.’s claim that Gøtzsche’s arguments against antidepressants represent a “new nadir in irrational polemic.” Gøtzsche highlights key evidence in support of his arguments “so that readers can judge for themselves what they think about the defence of these drugs by Nutt and colleagues.”

Gøtzsche first argues the effectiveness of antidepressants is minimal. Reviews by the FDA and Cochrane have shown only 10% of patients show a response to antidepressants compared to placebo. Closer analysis suggests even this small effect may be an exaggeration. The outcomes used in antidepressant studies rely on subjective assessments by patients and/or caregivers and are particularly susceptible to the placebo effect. In trials where an active placebo was used — for instance, atropine, like many antidepressants, causes dry mouth, so its use as placebo more carefully prevents patients from discovering whether they are receiving active treatment — the benefits of antidepressants were clinically insignificant. Gøtzsche argues there is no good evidence to support antidepressants’ role in suicide prevention, as both observational and randomized trial data indicate suicidal behavior is increased with antidepressants.

Importantly, these drugs — and here, Gøtzsche focuses particularly on SSRIs — carry significant side effects. In one study, 59% of patients reported sexual side effects, and in many randomized trials, patients stop taking the drug. These drugs also create chemical dependence, so removing them can cause severe, long-lasting withdrawal symptoms. Elderly patients  may experience additional side effects, including an increased number of falls; one trial found that SSRI treatment was associated with one additional death for every 28 patients treated over age 65.

In sum, Gøtzsche argues SSRIs have minimal or even nonexistent benefits (particularly in those with mild or moderate depression) and clear side effects; if they are to be used at all, they should be used temporarily, with a plan established up front to get patients off the drugs over time. He believes their widespread use results largely from “widespread crime committed by drug companies, including fraud, illegal promotion, and corruption of psychiatrists” rather than any evidential basis.