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The challenges in the management of treatment-resistant rapid-cycling bipolar disorder are multifaceted and represent a significant burden to the patient. There is a need for more exploration into the potential utility of various combination therapies in the setting of severe affective states. A 52-year-old woman with a history of severe treatment-resistant rapid-cycling bipolar affective disorder (BPAD) was hospitalized for the treatment of a severe mixed episode. The introduction of lamotrigine and clozapine in combination proved remarkably effective and well tolerated in both the acute management and in subsequent maintenance. The patient has remained asymptomatic during the 5-year follow-up without any further mood disturbance. Lamotrigine and clozapine are among the less-prescribed agents for BPAD and there is as yet little research into their use in combination. It is possible that these agents have complementary modes of action on various facets of the affective pathology, resulting in superior mood stabilization in this patient. [ABSTRACT FROM PUBLISHER]