Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena

1. The authors review the literature describing acute symptomatology produced by the gradual or abrupt withdrawal of heterocyclic antidepressants, monoamine oxidase inhibitors (MAOI) and neuroleptics. 2. Withdrawal of heterocyclic antidepressants and antipsychotic agents causes similar symptomatology. Symptoms produced by the discontinuation of these drugs include nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. 3. Psychotic relapse is often presaged by anxiety, agitation, restlessness, and insomnia. Prodromal symptoms are distinguished from the effects of neuroleptic withdrawal by a temporal relationship of the latter to reductions in the dosage or discontinuation of antipsychotic agents. 4. Withdrawal of MAOIs can result in severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium, and paranoid psychosis. 5. MAOI withdrawal phenomena resemble the symptoms produced by the discontinuation of chronically administered psychostimulants. 6. The capacity of MAOIs to exert amphetamine-like effects presynaptically and the propensity of somatic treatments for depression to subsensitize presynaptic receptors regulating the release of catecholamines provide a basis for the development of psychotic symptoms upon the withdrawal of MAOI. Evidence for this hypothesis is reviewed.