Effects of carbamazepine and valproate on haloperidol plasma levels and onpsychopathologic outcome in schizophrenic patients

The objective of this study was to compare the effects of carbamazepine (CB Z) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this control led clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia ( N = 24) or schizoaffective disorder (N = 3) were randomly assigned to recei ve 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ , or haloperidol with WA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma level s. Clinical state was rated by the Positive subscale of the Positive and Ne gative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monoth erapy. WA had no significant effect on either plasma levels or on psychopat hology, Our results suggest that comedication with haloperidol and CBZ is a ssociated with a high risk for treatment failure. This' might be a result o f a pharmacokinetic interaction on the hepatic level. The concomitant use o f VPA with neuroleptic therapy is not impaired by clinically significant dr ug interactions, but it is not associated with a better outcome under our c onditions.