A Double-Blind Randomized Trial of Mood Stabilizer Augmentation Using Lamotrigine and Valproate for Patients With Schizophrenia Who Are Stabilized and Partially Responsive

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To compare the efficacy of mood stabilizer augmentation of an antipsychotic for patients with schizophrenia who are both stabilized and partially responsive.


Adult patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia or schizoaffective disorder were enrolled in a 12-week, double-blind randomized trial. Patients were stabilized on an antipsychotic, and dose remained constant. Patients were randomly assigned to 1 of 3 adjunctive treatments: (1) with lamotrigine, (2) with divalproex sodium, or (3) with placebo. Efficacy assessments included the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, a Demoralization Scale, and the Clinical Global Impression severity and improvement scores. The Lehman quality of life improvement scale was used to assess quality of life and social functioning. Ratings were done at each study visit, including the last visit when they had been tapered off the adjunctive treatment.


There were no differences in global outcomes, symptoms, quality of life, or demoralization among the 3 groups. Short-term adverse effects were minimal.


Augmenting antipsychotics with the mood stabilizers of lamotrigine or divalproex sodium for most partially responsive patients with chronic schizophrenia did not seem to be a useful treatment strategy for improving the residual symptoms. The small sample size limits firm conclusions.

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