title: Preliminary controlled trial of nimodipine in ultra-rapid cycling affective dysregulation.
abstract: We report the initial results of the first controlled double-blind trial of nimodipine, a calcium channel antagonist, in the acute and prophylactic treatment of patients with treatment-refractory affective dysregulation. Active drug nimodipine (A) was substituted for placebo (B) in 12 patients. Patients were studied in a B-A-B design, with 3 of the 12 patients rechallenged with active drug in a B-A-B-A design (patients 9, 10, and 11). Five of the nine patients who completed the drug trial responded. One of three patients suffering from ultra-ultra-rapid (ultradian) cycling bipolar II disorder (patient 6) showed an essentially complete response; the other two ultradian patients (patients 4 and 9) showed evidence of a partial response on manic and depressive oscillations, one of which was confirmed in a B-A-B-A design. Only one of five less rapidly, but continuously cycling patients showed an excellent response (patient 10), and this was confirmed in a B-A-B-A design. The one patient who had recurrent brief depression (patient 11) showed a complete resolution of severe depressive recurrences, with response re-confirmed in an extended prophylactic trial with a B-A-B-A design. In the eight patients who completed self-ratings, nimodipine was associated with a significant reduction in the magnitude of mood fluctuations compared with the baseline placebo condition. Further clinical study of nimodipine, a calcium channel blocker with a unique profile of behavioral and anticonvulsant properties, appears warranted in patients with treatment-refractory affective illness characterized by recurrent brief depression and ultradian cycling.
authors.affiliation: Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
authors.forename: P J
authors.initials: PJ
authors.lastname: Pazzaglia
authors.forename: R M
authors.initials: RM
authors.lastname: Post
authors.forename: T A
authors.initials: TA
authors.lastname: Ketter
authors.forename: M S
authors.initials: MS
authors.lastname: George
authors.forename: L B
authors.initials: LB
authors.lastname: Marangell
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000009:adverse effects / Q000627:therapeutic use*; D010507:Periodicity; D011569:Psychiatric Status Rating Scales; D012008:Recurrence
chemical_list: D009553:Nimodipine