Eleven studies that addressed the question of reuptake-blocker antidepressant prophylaxis are examined. In all the studies, there was a higher incidence of depression recurrence in the antidepressant-discontinued group than in the antidepressant-maintained group. Although the findings from these studies are consistent with the explanation of the efficacy of antidepressant prophylaxis, an alternative explanation is that the findings demonstrate antidepressant drug withdrawal. Factors consistent with the antidepressant withdrawal explanation are discussed. A research design allowing for a definitive test of prophylaxis is proffered.