Does Lithium Improve Agitation After Valproate in Schizophrenia?

Case report suggests benefit in behavioral symptoms with lithium augmentation following adverse events with adjunctive therapy.

By
Andrea Surnit
April 23, 2026
2 min

MDSpire News

Objective:

To assess the effects of lithium augmentation on agitation and aggression in a single case of treatment-resistant schizophrenia after discontinuation of valproate.

Approach:

Key Findings:

Valproate improved irritability and psychomotor agitation but caused hypoglycemia and pancytopenia, which resolved after discontinuation.
Lithium augmentation led to a decrease in agitation and dangerous behaviors after reaching a serum level of 0.8 mEq/L.
BPRS total score improved from 80 to 64, with notable reductions in hostility and excitement.

Interpretation:

Improvements were primarily in behavioral symptoms rather than core psychotic features, with hallucinations and delusions persisting, suggesting potential benefits of lithium in managing agitation in this context.

Limitations:

Single-case design limits generalizability and causality establishment.
Potential confounding factors included changes in antipsychotic dosage, the inpatient environment, and the natural course of illness.

Conclusion:

This case highlights the clinical challenges of using mood stabilizers in residual-phase schizophrenia, emphasizing the need for further research on their efficacy in this specific patient population.