title: Clomipramine augmentation in treatment-resistant depression.
abstract: In depression that is resistant to tricyclic antidepressant (TCA) therapy, the substitution of a selective serotonin re-uptake inhibitor (SSRI), clomipramine, or a monoamine oxidase (MAO) inhibitor has been recommended. However, adding an additional antidepressant medication from a different drug class may produce even more rapid efficacy. In this regard, the combination of a MAO inhibitor or a SSRI plus a TCA has been shown to be of value in treatment-resistant depression (TRD). In this report, we examined the efficacy of clomipramine augmentation in 20 patients who failed to respond to either a MAO inhibitor or fluoxetine therapy for at least a 6-week period, and compared this to a third group given MAO inhibitor plus a conventional TCA. Two out of 9 (22%) MAO inhibitor/clomipramine patients and 4 out of 11 (36%) fluoxetine/clomipramine patients improved (Fisher's Exact test, P = ns), compared to 3 out of 7 (43%) patients taking MAO inhibitor/TCA (P = ns). However, the MAO inhibitor/clomipramine group experienced significantly more adverse events which necessitated stopping treatment (56%) when compared to the fluoxetine/clomipramine (9%) and compared to the MAO inhibitor/TCA group (0%) (chi 2 = 8.9, df = 2, P < 0.05). These adverse events included several cases of serotonin syndrome of mild to moderate severity. These observations indicate that clomipramine augmentation of a failed MAO inhibitor trial is of marginal efficacy (compared to augmentation with a conventional TCA) and should be employed with extreme caution.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Amsterdam
authors.forename: F
authors.initials: F
authors.lastname: García-España
authors.forename: M
authors.initials: M
authors.lastname: Rosenzweig
mesh_terms: D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002997:Clomipramine / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000188:drug therapy*; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D012189:Retrospective Studies; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors