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Antidepressant Withdrawal Syndromes: Evidence Supporting the Cholinergic Overdrive Hypothesis

The authors present case examples of the various antidepressant withdrawal syndromes. Substantial evidence supports the contention that these syndromes result from cholinergic overdrive; thus, they may have a common pathophysiological basis. Even paradoxical reactions on antidepressant withdrawal, such as mania, are consistent with the cholinergic overdrive hypothesis. If the cholinergic overdrive hypothesis is accepted, antidepressant withdrawal phenomena lend support to the cholinergic-adrenergic hypothesis of affective illness. The cholinergic overdrive hypothesis is both of considerable heuristic value and is further testable by the study of the tonic and phasic aspects of sleep and neuroendocrine parameters in the withdrawal state.