Oxcarbazepine as an Adjunct for Schizophrenia

To the Editor: Despite recent advances, about a quarter of all acutely ill schizophrenic patients still fail to respond to psychopharmacological treatment, even with the newer antipsychotic agents, and side effects remain frequent (1).

The adjunctive administration of anticonvulsant drugs, such as carbamazepine, divalproex, and lamotrigine, has been proposed as a useful treatment strategy for these patients but remains controversial. Under controlled conditions, carbamazepine showed adjunctive effects to antipsychotic treatment (2). The newer anticonvulsant oxcarbazepine represents a prodrug of 10-OH-carbamazepine, the active metabolite of carbamazepine, and shows even better tolerability. So far, it has been investigated only in the treatment of affective disorders.

We report an open-label case series of six male inpatients (mean age=29.8 years, SD=9.1) who had minimal or no response to antipsychotic treatment throughout 6 weeks of treatment and were not given clozapine for various reasons. Written informed consent was obtained in all cases. All patients were taking the maximum tolerated dose of the respective antipsychotic drug with sufficient plasma levels (initial treatment: one taking olanzapine, 20 mg/day; one, amisulpride, 600 mg/day; four, quetiapine 500–900 mg/day). They were monitored with use of the Brief Psychiatric Rating Scale (BPRS). Oxcarbazepine was added to antipsychotic treatment, starting with 300 mg/day and ending with a final dose of 900 to 2100 mg/day (mean=1500 mg/day, SD=465), with a transient headache as a side effect in a single case.

BPRS scores were decreased significantly from baseline (mean=58.7, SD=12.8) after 42 days of adjuvant treatment (mean=36.3, SD=9.2) (p=0.007, Student’s t test).

Despite their limitations, these data raise preliminary evidence for the adjuvant effects of oxcarbazepine in the acute treatment of schizophrenia. There is no relevant pharmacokinetic interaction between olanzapine, amisulpride, or quetiapine and oxcarbazepine (3, 4). Thus, the clinical synergism is most likely due to pharmacodynamic effects. The good tolerability of oxcarbazepine may have benefit in both treatment-resistant and acutely ill patients with slow treatment response.