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Lithium Plus Valproate as Maintenance Polypharmacy for Patients With Bipolar I Disorder: A Review

Published online by Cambridge University Press:  07 November 2014

David A. Solomon
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Gabor I. Keitner
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Christine E. Ryan
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Ivan W. Miller
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island

Extract

Standard pharmacotherapy for the maintenance of treatment of patients with bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of these agents, and as a result, psychiatrists often resort to polypharmacy. Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug combination that warrants further study as maintenance therapy is lithium plus valproate. Each is approved by the U.S. Food and Drug Administration for treatment of acute mania, and lithium has demonstrated efficacy for maintenance treatment as well. Some preliminary evidence suggests that the combination can be effective for patients who do not respond to monotherapy, and it seems to be no more dangerous than monotherapy. Concomitant administration of lithium plus valproate does not significantly alter lithium pharmacokinetics, and statistically significant changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to augment response, many of their effects in the central nervous system do differ, and there is no indication of pharmacodynamic interactions that oppose each other. Finally, some evidence suggests that lithium and valproate may differ with regard to clinical variables that predict response to treatment. (J Clin Psychopharmacol 1998;18:38–49)

Bipolar I disorder afflicts approximately 1% of the U.S. adult population, with a median age at onset of 19 years. In many respects, it is a disabling disease. Acute episodes of mania and depression are often protracted with 24% of patients still acutely ill after 1 year has elapsed, 16% after 2 years, and 9% after 5 years. Subsyndromal symptoms, which impose significant morbidity that falls short of meeting full criteria for a mood episode, may occur frequently. Patients with bipolar I disorder are more likely than not to be unemployed or underemployed, less likely to marry and more likely to divorce than matched control subjects, and almost every family perceives the illness as a burden. Even remitted patients manifest poor psychosocial functioning, Ultimately, nearly 19% of patients die from suicide.

Type
Academic Supplement
Copyright
Copyright © Cambridge University Press 2000

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