In just over half of the published and unpublished studies, Kirsch and colleagues reported in 2002, the drug alleviated depression no better than a placebo. "And the extra benefit of antidepressants was even less than we saw when we analyzed only published studies," Kirsch recalls. About 82 percent of the response to antidepressants--not the 75 percent he had calculated from examining only published studies--had also been achieved by a dummy pill.On the other hand, there is also evidence that SSRIs have other interesting effects on the brain. Jonah Lehrer:
The extra effect of real drugs wasn't much to celebrate, either. It amounted to 1.8 points on the 54-point scale doctors use to gauge the severity of depression, through questions about mood, sleep habits, and the like. Sleeping better counts as six points. Being less fidgety during the assessment is worth two points. In other words, the clinical significance of the 1.8 extra points from real drugs was underwhelming. Now Kirsch was certain. "The belief that antidepressants can cure depression chemically is simply wrong," he told me in January on the eve of the publication of his book The Emperor's New Drugs: Exploding the Anti-depressant Myth.
The 2002 study ignited a furious debate, but more and more scientists were becoming convinced that Kirsch--who had won respect for research on the placebo response and who had published scores of scientific papers--was on to something. One team of researchers wondered if antidepressants were "a triumph of marketing over science." Even defenders of antidepressants agreed that the drugs have "relatively small" effects. "Many have long been unimpressed by the magnitude of the differences observed between treatments and controls," psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote--"what some of our colleagues refer to as 'the dirty little secret.' " In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.
But just because antidepressants don't work via some silly and obsolete chemical model of depression doesn't mean the drugs don't trigger important changes in the brain. In recent years, scientists have found that the little blue pills modulate the neural pathways of plasticity, up-regulating trophic factors and neurogenesis. Because they make our mind more malleable - and help counter the the toxic effects of stress - the drugs have potential implications far beyond the treatment of depression.