When clozapine is not enough: Augment with lamotrigine?

Stabilizing glutamate transmission may benefit some patients with treatment-resistant schizophrenia.

John A. Gray, MD, PhD
Resident, department of psychiatry, postdoctoral fellow, department of cellular and molecular pharmacology, University of California, San Francisco

Samuel C. Risch, MD
Professor, department of psychiatry, University of California, San Francisco

Current antipsychotics are reasonably effective in treating positive symptoms, but they do less to improve the negative and cognitive symptoms that contribute to patients’ long-term poor functional capacity and quality of life. So what do psychiatrists do in clinical practice to mitigate antipsychotics’ limitations? We augment.

Schizophrenia patients routinely are treated with polypharmacy—often with antidepressants or anticonvulsants—in attempts to improve negative symptoms, aggression, and impulsivity. Most adjuncts, however—including divalproex, antidepressants, and lithium—have shown very small, inconsistent, or no effects. The only agent with a recent meta-analysis supporting its use as augmentation in treatment-resistant schizophrenia is lamotrigine, an anticonvulsant approved for use in epilepsy.

This article examines the evidence supporting off-label use of lamotrigine as an augmenting agent in schizophrenia and explains the rationale, based on lamotrigine’s probable mechanism of action as a stabilizer of glutamate neurotransmission.

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