CNS Drugs 2007; 21 (5): 426-427GUEST COMMENTARIES 1172-7047/07/0005-0426/$44.95/0

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study. Paliperidone ER should have less potentialPaliperidone Extended Release for drug interactions than the parent compound ris-A Viewpoint by George Simpsonperidone, although this is not a serious problem with

Department of Psychiatry and the Behavioralrisperidone treatment. There is a dose-dependentSciences, Keck School of Medicine, Universityresponse with regard to adverse effects, in particularof Southern California, Los Angeles,serum prolactin levels and EPS. The main advantageCalifornia, USAof this extended-release formulation is that it can be

For over 50 years, antipsychotic agents havestarted at a therapeutic dosage and administeredplayed a key role in the treatment of schizophrenia.once daily.The simultaneous discovery of their ability to reduce

One interpretation of the CATIE (Clinical An-or eliminate the positive symptoms of schizophreniatipsychotic Trials of Intervention Effectiveness)and at the same time cause extrapyramidal symp-

toms (EPS) indistinguishable from classical parkin- study would be that a drug started at or above asonism was a major advance in 20th century thera- therapeutic dose, if it is well tolerated by the patient,peutics. To an extent, these agents have been sup- may be effective for the length of the study. If so,planted by atypical agents following the discovery then paliperidone ER may be more effective thanof clozapine, with its antipsychotic effect in the quetiapine, risperidone or ziprasidone, all of whichabsence of EPS. have to be titrated. In contrast, olanzapine can be

A range of atypical agents have been developed given at high dosages and is well tolerated; paliper-since that time. The first agent was risperidone, idone ER appears to be well tolerated at therapeuticwhose active metabolite is paliperidone (an hydroxy dosages. However, given that there is a dose re-metabolite). Therefore, the efficacy of paliperidone sponse for adverse effects, this would have to beshould be the same as, or very similar to, that of taken into consideration in the starting dosage ofrisperidone. This would appear to be the case. The

paliperidone ER. Clearly paliperidone ER 3 mg/daystudies conducted so far show that the special for-

appears to be effective, paliperidone ER 6 mg/daymulation of paliperidone (extended release [ER])should suffice for most people and higher dosagespermits once-daily administration of this agent, iscan be given if the response is inadequate. Head-to-more effective than placebo in studies in patientshead trials will be required to define its place in thewith acute symptoms of schizophrenia and delaystreatment of patients with schizophrenia. ▲relapse compared with placebo in one longer term