CLOZAPINE IN TREATMENT OF RESISTANT SCHIZOPHRENIA improvement in 40-60% of patients over a period of 1.5 to 6 months (Lindstrom,1988; Meltzer et a!.1989; Mattes, 1989; Brier et al.,1993). These studies also reported that the benefits occurred in the early phase of treatment and stabilised in the initial 3-6 months after which, no further benefit was seen. It also remains to be seen whether the patients in our study would have shown further improvement or reached a plateau as the study was terminated at this point. Clozapine became unpopular due to its dangerous side effect of agranulocytosis, which is reversible in early stages with a maximum risk being in the first 18 weeks of treatment (Anderman,1977; Andrew & Rennie,1990). Fortunately, none of our patients developed this potentially dangerous side effect. Lieberman et al.(1988) cited a 2% cumulative incidence after 52 weeks of clozapine treatment for agranulocytosis. However, benign leucocytosis can occur in the initial stages, which was also seen in our study (Kaplan et al.,1996). Sedation, sialorrhoea, dizziness and hypotension were the most commonly seen side effects in our patients, a fact which was also reported in previous studies (Fitton & Heel,1990; Brier et al.,1994). 42% of our patients complained of weight gain, keeping in with the study by Umbricht et al. (1994). Most of these low dose side effects are associated with clozapine titration and tend to lessen and disappear when dosage reaches 300-400 mg/day. However, we did not notice much diminution in the frequency of the observed side effects during our study period. The data on the dose range of clozapine revealed a lower mean dose of 241 mg/day, in the Indian population as per our study which was similar to the trial conducted in Europe where the mean dose was 283 mg/day. However, studies in the US revealed higher mean dose of 444 mg/day though the response rate was strikingly similar (Fleischhacker,1994). This finding is significant because if patients can be maintained on a lower dose then the toxic side- effects can be avoided. In conclusion, this trial was conducted to study the efficacy of clozapine in treatment resistant schizophrenics does propagate the benefits of the drug. It also reveals that there are no dangerous side effects of the drug except for sedation and sialorrhoea which may decrease with clozapine titration. The required mean dose in our study was much less than in the western counter parts. Though the study sample was small and screened over 3 months, a larger sample with an adequate time span would be more fruitful in yielding the shortcomings of the present study. REFERENCES American Psychiatric Association (1994) Diagnosis and Statistical Manual of Mental Disorder, Edn.4, Washington DC: A.P.A. Anderman,B. & Griffith,R.W.(1977) Clozapine induced agranulocytosis - a situation report upto August. European Journal of Psychiatry, 11, 199-201. Andrew, F. & Rennie, C.H. (1990) Clozapine. Drugs, 40,5, 722-747. Brier, A., Buchmann, R.W., Irish, D. & Carpenter, W.T. Jr.(1993) Clozapine treatment of outpatients with the schizophrenia, outcome and long term response patterns. Hospital Community Psychiatry, 44, 1145-1149. Brier,A., Buchmann,R.W. & Kirkpatric, B. (1994) Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. American Journal of Psychiatry, 151,20-26. Conley.R., Gounaris.C. & Tamminga.C. (1994) Clozapine response varies in deficit versus non-deficit schizophrenic subjects. Biological Psychiatry, 35, 746-747. Fitton.A. & Heel,R.C.(1990) Clozapine. A review of its pharmacological properties and therapeutic use in schizophrenia. Drug, 40,5, 722-747. Fleischhacker,W.W., Munamer.M. & 339