ZOTEPINE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC EFFICACY IN THE MANAGEMENT OF SCHIZOPHRENIA

Zotepine is an atypical antipsychotic with high affinity for serotonin 5-HT2A and 5-HT2C and dopamine D-2, D-3, D-1 and D-4.2 receptors and is a potent inhibitor of reuptake of noradrenaline (norepinephrine). T he major metabolite of zotepine, norzotepine is pharmacologically acti ve and possesses affinity for dopaminergic receptors similar to the pa rent compound. Pharmacodynamic data suggest that at low doses the drug increases dopaminergic neurotransmission, while at higher doses it ac ts as a dopaminergic receptor antagonist. In double-blind trials zotep ine 150 to 300 mg/day was as effective as typical antipsychotics such as haloperidol, chlorpromazine, perazine and thiothixene in controllin g symptoms of schizophrenia Although improvement occurred with both zo tepine and haloperidol in patients with predominantly negative schizop hrenic symptoms, only zotepine achieved significant reductions in most individual negative symptom scores versus baseline. Results from 1 st udy suggest that maintenance therapy with zotepine for up to 1 year wa s effective in preventing relapse in schizophrenic patients. In 2 tria ls in patients with treatment-resistant schizophrenia, some improvemen t occurred in most patients after the initiation of zotepine either in place of previous drugs or as add-on therapy. Zotepine is generally w ell tolerated; constipation, dry mouth, insomnia, sleepiness, asthenia and bodyweight gain are the commonly encountered adverse effects. The incidence of extrapyramidal symptoms with zotepine is low (8 to 29%) and significantly less than that seen with haloperidol and chlorpromaz ine; however there were no differences between zotepine and some other typical antipsychotics in this respect. Dosages greater than or equal to 300 mg/day are associated with an increased risk of generalised co nvulsions. Thus, zotepine is as effective as typical antipsychotic age nts in the management of acute exacerbations of schizophrenia and may be useful for the prevention of relapse. Initial trials have found the drug to be effective in the management of patients with negative schi zophrenic symptoms and those with treatment-resistant schizophrenia.