Indian Journal of Psychiatry, 1999, 41 (4), 336-340 AN OPEN STUDY OF CLOZAPINE IN THE TREATMENT OF RESISTANT SCHIZOPHRENIA NEENA DESAI, VANl JAIN, SUPRIYA GHALSASI MADHUSUDAN DALVI & SEJAL KELKAR ABSTRACT This open study was undertaken to assess the efficacy ofclozapine in resistant schizophrenics, its side effects and safety profile and the mean dose required. Sample consisted of 28 patients who had been previously treated with neuroleptics and ECTs. A special proforma was prepared for recording the psychopathology and side effect profile. The complete blood count, differential count and BPRS scores were recorded weekly for a period of 3 months. Within 1 month of treatment on a dose range of 100-200 mg/day a 25%-50% decline in the BPRS score was noticed, the mean dose required was 241 mg/day. Sedation and sialorrhoea constituted the commonest side effects in 90% patients. No case of agranulocytosis was reported. The implications of the study are discussed. Key words : Clozapine, treatment resistant schizophrenia The introduction of typical neuroleptic agents in 1950 was a dramatic advance to treat patients with schizophrenia. Despite this a deterioration in the level of functioning and associated side-effects of neuroleptics still continue to be a problem in many schizophrenics. A relapse rate of 15-20% also occurs every year (Kane et al.,1988). Clozapine has been recommended in patients who are resistant to or intolerant of typical neuroleptics. According to Kane (1992) and Meltzer (1992), failure to respond to atleast two and/or three typical neuroleptics given for atleast 6 weeks each, should be considered as treatment resistant schizophrenia. The most exciting current development is the re-emergence of clozapine as a highly effective atypical antipsychotic drug for the treatment of resistant schizophrenics. Clozapine is a dibenzodiazepine with pharmacological and therapeutic profile that distinguishes it from classical antipsychotics like phenothiazines, butyrophenones, diphenyl butylpiperidines and thioxanthines. In contrast to these later groups, clozapine by virtue of its chemical structure exerts a weak antagonism at central dopami.ie D2 receptors and more pronounced inhibition of dopamine D, mediated activation of adenylate cyclase and potent blockade of central serotonergic, adrenergic and cholinergic receptors (Kaplan & Saddock,1996). More over, clozapine is only marginally effective in several animal behavioural models (e.g. induction of catalepsy and suppression of dopamine induced stereotypy). Early enthusiasm about the drug was marred by recognition in 1970, that it caused agranulocytosis. Only recently a sufficiently compelling data has been gathered that clozapine can be used safely if special surveillance is undertaken to monitor its potentially severe toxic effects (Anderman & Griffith, 1997). In our search for better treatment options for resistant schizophrenia, clozapine has definitely provided a ray of hope. The present study was undertaken to study the (1) efficacy 336