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OBJECTIVE: To examine the efficacy of a slow-release formulation of diltiazem as adjunctive therapy in patients with treatment-resistant bipolar disorder. DESIGN: Retrospective study. PATIENTS: Eight female patients with treatment-resistant bipolar disorder. INTERVENTIONS: Patients were administered diltiazem and monitored for a 6-month period before starting diltiazem and a 6-month period after starting the drug. OUTCOME MEASURES: All patients were seen at least monthly and usually every 2 weeks. The frequency and severity of both depressive and manic episodes were examined during the 6-month period after starting diltiazem, and compared with those during the 6-month period before diltiazem treatment. RESULTS: There was a statistically significant decrease in the frequency and severity of both manic and depressive episodes in these patients after they started treatment with diltiazem, compared with the period before they started treatment with diltiazem (p < 0.001). There was no evidence of side effects requiring patient withdrawal or of drug interactions. CONCLUSIONS: The results support previous suggestions that calcium-channel antagonists may be an effective adjunctive treatment in the management of bipolar disorder. Further controlled clinical studies are needed to confirm this small, open-label, retrospective study.