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January 1997

Depression During Mania: Treatment Response to Lithium or Divalproex

Author Affiliations

From the Department of Psychiatry, University of Texas Medical School at Houston (Drs Swann and Dilsaver); the Department of Psychiatry, University of Texas Health Science Center at San Antonio (Dr Bowden); Abbott Laboratories Inc, North Chicago, Ill (Dr Morris); the Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio (Dr Calabrese); the Department of Psychiatry, University of Texas Southwestern Medical School at Dallas (Dr Petty); the Department of Psychiatry, University of Indiana School of Medicine, Indianapolis (Dr Small); and the Department of Psychiatry, University of Illinois at Chicago (Dr Davis).

Arch Gen Psychiatry. 1997;54(1):37-42. doi:10.1001/archpsyc.1997.01830130041008

Background:  Little information exists from controlled studies about clinical characteristics that predict treatment response in mania. The presence of depressive symptoms during manic episodes may be associated with poor response to psychopharmacological treatments. This is an investigation of the relation between depressive symptoms and treatment response in acute manic episodes.

Methods and Design:  In a parallel-group, doubleblind study, 179 patients hospitalized for acute manic episodes were randomized to receive divalproex sodium, lithium carbonate, or placebo (ratio, 2:1:2). The study was carried out at 9 academic medical centers. Patients had comprehensive evaluations of behavior and symptoms before and during 3 weeks of treatment. The primary outcome measure, change in mania factor scores derived from the Schedule for Affective Disorders and Schizophrenia: Change Version, was compared in pa- tients with and without depressive symptoms at baseline according to nurse- or physician-rated scales.

Results:  Depressive symptoms were associated with poor antimanic response to lithium and with better response to divalproex. This was not due to differences in overall severity of illness, substance abuse, gender, age, or history.

Conclusions:  These data suggest that even a modest level of pretreatment depression-related symptoms is a robust predictor of lithium nonresponse, and is associated with better response to divalproex. Although their overall efficacy in acute mania is similar, lithium and divalproex may be most effective in clinically and biologically distinct groups of patients.

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