A case report demonstrated that lithium augmentation may be associated with reduced agitation and aggression in a patient with treatment-resistant schizophrenia after valproate was discontinued because of hypoglycemia and pancytopenia.

In the case report, researchers described a single-patient case of a 49-year-old female patient with treatment-resistant schizophrenia in the residual phase, with persistent psychotic symptoms and behavioral dysregulation despite receiving antipsychotic therapy. The patient received adjunctive treatment with valproate augmentation followed by lithium augmentation after clozapine and electroconvulsive therapy were declined. Clinical outcomes were assessed using symptom changes and the Brief Psychiatric Rating Scale (BPRS).

The researchers assessed the patient for agitation, aggression, overall psychiatric severity, adverse events, and short-term clinical course. Valproate at 800 mg per day was associated with improvement in irritability and psychomotor agitation, but treatment was complicated by hypoglycemia and later pancytopenia. Both adverse events resolved following discontinuation; however, valproate withdrawal led to a worsening of behavioral symptoms that improved again with rechallenge.

Following discontinuation of valproate augmentation, lithium carbonate was initiated at 400 mg per day and titrated to 600 mg per day. The researchers noted that agitation and dangerous behaviors decreased after a serum level of 0.8 mEq/L was reached. The BPRS total score improved from 80 to 64, with reductions in hostility from 6 to 2 and excitement from 6 to 4. No psychiatric readmission occurred during 3 months of follow-up, although hallucinations and delusions persisted.

The researchers stated that improvements were primarily observed in behavioral symptoms rather than core psychotic features.

The findings were limited by the single-case design and the researchers couldn't establish causality. They noted potential confounding factors, including antipsychotic dose changes, inpatient environment, and the natural course of illness.

“This case highlights the clinical dilemma of mood stabilizer augmentation in residual-phase schizophrenia,” wrote lead study author Yoshiki Kasagi, MD, of the Department of Psychiatry at the University of Occupational and Environmental Health in Japan, and colleagues.

The study authors reported no conflicts of interest and no funding.

Source: PCN Reports