Clinical dilemma of mood stabilizer augmentation in treatment‐resistant schizophrenia with residual phase: A case report of valproate‐associated hypoglycemia and cytopenia, and subsequent lithium response

Background: Mood stabilizer augmentation is frequently used in treatment-resistant schizophrenia despite limited guideline recommendations. Evidence for its efficacy and safety in the residual phase, however, remains insufficient. Case Presentation: A 49-year-old Japanese woman with treatment-resistant residual schizophrenia exhibited persistent agitation and aggression despite antipsychotic therapy. Valproate augmentation (800 mg/day) improved irritability and psychomotor agitation but was complicated by hypoglycemia, suggestive of relative carnitine deficiency, and subsequent pancytopenia. Both adverse events resolved after discontinuation. Behavioral symptoms markedly worsened following withdrawal. Clozapine and electroconvulsive therapy were declined. Lithium augmentation (600 mg/day; serum level 0.8 mEq/L) was initiated, resulting in improvement of dangerous behaviors and agitation. The Brief Psychiatric Rating Scale total score improved from 80 to 64, particularly in the hostility and excitement items. No readmission to the psychiatric ward occurred during a 3-month follow-up. Conclusion: This case highlights the clinical dilemma of mood stabilizer augmentation in residual-phase schizophrenia. While valproate demonstrated behavioral efficacy, serious adverse events necessitated its discontinuation. Lithium may represent a potential alternative for managing aggression and agitation, but further research is warranted.