Potential sensitising effects of antidepressant drugs on depression

The possibility that antidepressant drugs, while effectively treating depression in the short term, may worsen its course through a sensitisation process has been proposed. Although this hypothesis has not been extensively tested, a number of clinical findings point toward this possibility: the very unfavourable long term outcome of major depression when treated by pharmacological means; paradoxical (depression-inducing) effects of antidepressant drugs in some patients with mood and anxiety disturbances; antidepressant-induced switching and cycle acceleration in bipolar disorder; the occurrence of tolerance to the effects of antidepressants during long term treatment; the onset of resistance upon rechallenge with the same antidepressant drug in some patients; and withdrawal syndromes following discontinuation of mood-elevating drugs. The occurrence of a process of sensitisation in susceptible individuals may be explained on the basis of the oppositional model of tolerance. Continued drug treatment may recruit processes that oppose the initial acute effects of a drug. When drug treatment ends, these processes may operate unopposed, at least for some time. This hypothesis is, however, substantially untested and its scientific exploration is likely to encounter considerable methodological and ideological difficulties. It needs to be verified by epidemiological studies, controlled clinical trials, follow-up studies and psychobiological investigations. The clinical implications of the sensitisation hypothesis in depression are considerable. The treatment of depression with antidepressant drugs would not be questioned, but its modalities and applications may undergo important changes. A number of current practices would need to be re-examined such as the (inappropriate) use of antidepressant drugs in minor mood disturbances, the treatment of anxiety disorders with antidepressants, the use of suboptimal dosages of antidepressant drugs, the application of antidepressants as prophylactic agents, and modalities of discontinuation. A cost-benefit appraisal of psychotherapeutic versus pharmacological treatment would also need to be, considered. Even though the hypothesis of sensitising effects of antidepressant drugs, at present, has no empirical support, it is important enough to deserve extensive studies and debate.