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.
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