Treatment of resistant schizophrenia with valproate and neuroleptic drugs

Four cases of resistant Schizophrenia treated with valproate association with different neuroleptic drugs (thioridazine in three cases and loxapine in one) are presented. After a mean period of three months with this treatment, clinical improvement, consisting in a reduction of positive symptoms, as measured by the BPRS, and a normalization of hostile/disruptive behavior, was observed, and hospital discharge was possible. Reduction of symptoms was still present after a follow-up of 4 to 24 months. As valproate is a drug with gabaergic properties, a GABA involvement in the pathogenesis of schizophrenia is discussed. The association of valproate to neuroleptic drugs should be considered in the treatment of resistant Schizophrenia.