Antidepressant withdrawal phenomena.

The authors review the antidepressant withdrawal literature. Withdrawal of tricyclic antidepressants may precipitate the development of discrete syndromes. The most common of these are general somatic or gastrointestinal distress with or without anxiety and agitation, sleep disturbance characterized by excessive and vivid dreaming and initial and middle insomnia, movement disorder, and psychic and behavioral activation extending on a continuum to frank mania. The etiology of these syndromes is discussed. The "cholinergic overdrive hypothesis" explains most antidepressant withdrawal phenomena, including infrequent manifestations. Some antidepressant withdrawal symptomatology may be due to an interaction between cholinergic overdrive and monoaminergic systems. A treatment program useful in ameliorating the distress of patients who develop antidepressant withdrawal symptoms and who cannot continue to take antidepressants is outlined. The theoretical significance of tricyclic withdrawal phenomena and the heuristic value of current hypotheses as to their pathophysiology are discussed.