Selective Serotonin Reuptake Inhibitors Withdrawal Syndromes: New Insights into Pathophysiology and Treatment

There has been increasing awareness of the withdrawal syndromes which may occur with discontinuation of the selective serotonin reuptake inhibitors (SSRI). The literature that is surveyed indicates that they are frequent, may vary from one SSRI to another, occur with either abrupt or gradual disconfirmation, and are not necessarily reversible. These phenomena may be explained on the basis of the oppositional model of tolerance. Continued drugs treatment may recruit processes that oppose the initial acute effect of a drug. When drug treatment ends, these processes may operate unopposed, at least for some time, induce withdrawal symptoms and increased vulnerability to relapse. The model may provide an explanation also for other clinical findings in depression treatment: tolerance to the effects of antidepressants during long-term therapy, onset of resistance upon rechallenge with the same antidepressant drug, paradoxical effects of antidepressants in some patients, switching and cycle acceleration in bipolar disorder, very unfavourable long-term outcome of major depression treated by pharmacological means. The implications for treatment of depression are considerable