Mood stabilizers in schizophrenia


We agree with Dr. Leslie Citrome that too few randomized trials have been done to conclude that mood stabilizers are effective in schizophrenia (Current Psychiatry, December 2004). We believe, however, that there is enough evidence to support augmenting antipsychotics with mood stabilizers in treatment-resistant cases.

Results from randomized, controlled trials (RCT) are the gold standard of evidence, but methodologic, logistic, and ethical drawbacks often limit RCTs of most drugs. Because mood stabilizer augmentation in schizophrenia is a relatively new strategy, we should not dismiss its use in treatment-resistant cases even if non-RCT evidence supports this use.

Although we often see schizophrenia as a single entity, we are dealing with a group of disorders with heterogeneous causes and variable presentations.1 Based on our work in forensic and challenging-behavior units in the United States and Europe, adjunctive mood stabilizers are usually targeted toward psychomotor agitation, aggression, and affective instability—often with significant benefit.

When hostility in schizophrenia is targeted, a randomized study has shown the advantages of a divalproex/antipsychotic combination over antipsychotic monotherapy.2 Unfortunately, most other evidence supporting mood stabilizer use in schizophrenia is retrospective, open-labeled, and uncontrolled.3

Clinicians should encourage funding for rigorous RCTs of mood stabilizers in schizophrenia. In the interim, clinical judgment should dictate which agents to use and when.

Babatunde Adetunji, MD
Attending psychiatrist
Kirby Forensic Psychiatric Center
New York, NY

Adedapo Williams, MD
Attending psychiatrist
John H. Stroger Jr. Hospital of Cook County
Chicago, IL

Maju Mathews, MD
Psychiatry resident
Drexel University College of Medicine
Philadelphia, PA

Thomas Osinowo, MD
Director of forensic services
Northcoast Behavioral Health Care
Toledo, OH


  1. Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry (9th ed). Philadelphia: Lippincott Williams and Wilkins, 2003:471.
  2. Citrome L. Casey DE, Daniel DG, et al. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. Psychiatr Serv 2004;55:290–4.
  3. Afaq I, Riaz J, Sedky K, et al. Divalproex as a calmative adjunct for aggressive schizophrenic patients. J Ky Med Assoc 2002;100:17–22.

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