A controlled study of mental disorders associated with epilepsy.
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Biomedical subjects
Publications and source records attributed to J G Small.
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A single-blind parallel study of 20 treatment-resistant hospitalized depressed patients showed that 10-30 mg/day molindone was more effective and less toxic than 20-30 mg tranylcypromine. Molindone-treated patients responded during the first week with particular improvement in anxiety symptoms and agitation. Extrapyramidal symptoms developed in half of the patients on molindone, which were effectively managed with amantadine. Early termination from the study because of clinical worsening or side effects occurred in seven patients on tranylcypromine and in none on molindone. These results suggest that molindone in low dosage may be helpful in the management of refractory depression and may have the further advantage of producing a more rapid response to treatment with fewer disabling side effects.
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OBJECTIVE: To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. DESIGN: Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. PATIENTS: A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. INTERVENTIONS: After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. MAIN OUTCOME MEASURES: Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. RESULTS: Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. CONCLUSIONS: Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.
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