Antidepressant discontinuation manic states: a critical review of the literature and suggested diagnostic criteria

We critically appraised all published reports of hypomania and mania following antidepressant termination. To increase reliability and validity we devised diagnostic criteria for an antidepressant discontinuation or withdrawal 'manic state' based primarily on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition substance withdrawal criteria. A systematic literature review identified 24 reports meeting our criteria. Mean age was 39 years (range 18-74), men and women were approximately equally represented, and more cases involved people with unipolar (n = 19) than bipolar disorder (n = 4). The median duration of preceding antidepressant treatment was 12 weeks (range 4 weeks-12 years). All major antidepressant classes were involved (tricyclic antidepressants = 13; selective serotonin reuptake inhibitors 5; monoamine oxidase inhibitors = 3; selective serotonin-norepinephrine reuptake inhibitors = 2; miscellaneous = 1). More cases followed abrupt antidepressant withdrawal (n = 11) than a tapered withdrawal (n = 6). Six cases appeared to meet the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for a manic episode, with two cases requiring inpatient admission. Of the 24 cases, nine resolved spontaneously without treatment (median duration = 25.5 days), six responded to antimanic drugs, four resolved following antidepressant reinstatement, and treatment was unclear in five cases. We conclude that antidepressant discontinuation hypomania/mania is a valid syndrome. It should be added to the differential diagnosis of hypomania/mania. The clinical implications and possible mechanisms are discussed.