Shortly after Prozac became the best-selling drug in the world in the early 1990s, I proposed that there was little or no evidence for efficacy, but considerable evidence that the drug would worsen depression and cause severe behavioral abnormalities. I attributed much of the problem to "compensatory changes" in neurotransmitters as the brain resists the drug effect. Since then, in a series of books and articles , I've documented antidepressant-induced clinical worsening and some of its underlying physical causes. Now the idea has gained ground in the broader research community and has recently been named "tardive dysphoria."

A recent scientific study by El-Mallakh and his colleagues reviewed the antidepressant literature and concluded that any initial improvements are often followed by treatment resistance and worsening depression. They compare this problem to tardive dyskinesia, caused by antipsychotic drugs, and call it tardive dysphoria, "an active process in which a depressive picture is caused by continued administration of the antidepressant." Based on rat studies, they hypothesize that "dendrite arborization" -- an increased branching growth of nerve cells -- caused by chronic antidepressant exposure, may be the cause.



In a meta-analysis of 46 studies, Andrews et al. (2011) found the relapse rate for antidepressant-treated patients (44.6 percent) was much higher than for placebo-treated patients (24.7 percent). Andrews also found that the more potent antidepressants caused an increased risk of relapse on drug discontinuation. A 2010 Minnesota evaluation of patient care in the state found that only 4.5 percent of more than 20,000 patients were in remission at 12 months, indicating that they had become chronically afflicted with depression during and probably as a result of their treatment.