PRELIMINARY CONTROLLED TRIAL OF NIMODIPINE IN ULTRA-RAPID CYCLING AFFECTIVE DYSREGULATION

We report the initial results of the first controlled double-blind tri al of nomodipine, a calcium channel antagonist, in the acute and proph ylactic treatment of patients with treatment-refractory affective dysr egulation. 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 (patien ts 9, 10, and 11). Five of the nine patients who completed the drug tr ial responded. One of three patients suffering from ultra-ultra-rapid (ultradian) cycling bipolar II disorder (patient 6) showed an essentia lly complete response; the other two ultradian patients (patients 4 an d 9) showed evidence of a partial response on manic and depressive osc illations, one of which was confirmed in a B-A-B-A design. Only one of five less rapidly, but continuously cycling patients showed an excell ent response (patient 10), and this was confirmed in a B-A-B-A design. The one patient who had recurrent brief depression (patient ii) showe d a complete resolution of severe depressive recurrences, with respons e re-confirmed in an extended prophylactic trial with a B-A-B-A design . In the eight patients who completed self-ratings, nimodipine was ass ociated with a significant reduction in the magnitude of mood fluctuat ions compared with the baseline placebo condition. Further clinical st udy of nimodipine, a calcium channel blocker with a unique profile of behavioral and anticonvulsant properties, appears warranted in patient s with treatment-refractory affective illness characterized by recurre nt brief depression and ultradian cycling.