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Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana, and Department of Psychiatry and Human Behavior, University of Mississippi, Jackson, Mississippi;

Eileen Brown, PhD

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana;

Hagop S. Akiskal, MD

International Mood Center, Department of Psychiatry, University of California at San Diego, San Diego, California;

Joseph R. Calabrese, MD

Department of Psychiatry, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio;

Terence A. Ketter, MD

Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California;

Leslie M. Schuh, PhD

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana;

Paula T. Trzepacz, MD

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana, Department of Psychiatry and Human Behavior, University of Mississippi, Jackson, Mississippi, and Department of Psychiatry, Tufts University Medical School, Boston, Massachusetts;

John G. Watkin, DPhil

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana;

Mauricio Tohen, MD DrPH

Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana, and Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, Massachusetts, USA

Correspondence: Dr Rober Robertt Baker, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. Fax: +317 276 7100; e-mail: robertbaker{at}lilly.com

Declaration of interest R.W.B., E.B., L.M.S.,P.T.T.,J.G.W. and M.T. are employees of Eli Lilly and Company.

Background Few controlled studies examine the treatment of depressive features in mania.

Aims To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.

Method Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5–20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes. This analysis focused on a dysphoric subgroup with baseline Hamilton Rating Scale for Depression (HRSD) total scores of 20 or over contrasted with non-dysphoric patients.

Results In the dysphoric subgroup (n=85) mean HRSD total score improvement was significantly greater in olanzapine co-therapy patients than in those receiving placebo plus lithium or valproate (P<0.001). Substantial contributors to this superiority included the HRSD Maier sub-scale (P=0.013) and the suicide item (P=0.001). Total Young Mania Rating Scale improvement was also superior with olanzapine co-therapy.

Conclusions In patients with acute dysphoric mania, addition of olanzapine to ongoing lithium or valproate monotherapy significantly improved depressive symptom, mania and suicidality ratings.

This article has been cited by other articles:

				A. Streeruwitz, T. R. E. Barnes, J. Fehler, R. Ohlsen, and V. A. Curtis Pharmacological management of acute mania - does current prescribing practice reflect treatment guidelines? J Psychopharmacol, March 1, 2007; 21(2): 206 - 209. [Abstract] [PDF]

				P. Hosalli and M. Jayaram Olanzapine co-therapy in bipolar disorder The British Journal of Psychiatry, November 1, 2005; 187(5): 486 - 487. [Full Text] [PDF]

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