CLOZAPINE IN TREATMENT OF RESISTANT SCHIZOPHRENIA of clozapine (2) side effects and safety profile of clozapine and (3) mean effective dose required for the Indian setting. MATERIAL AND METHOD In an open and non-comparative study, the sample consisted of randomly selected 28 patients who were attending the outpatients department of psychiatry, of a general municipal hospital. All the patients satisfied the DSM-IV criteria for schizophrenia (APA.1994). They were either chronic or acutely relapsed schizophrenics or those who were prone for the extra pyramidal side effects of potent neuroleptics. These patients were previously treated for a minimum of eight weeks with at least two neuroleptics viz, chlorpromazine (1000 mg/day or more), haloperidol or trifluoperazine in dose equivalents of 1000 mg/day of chlorpromazine and a course of 6-10 ECTs. None of the patients were on long term depot preparations. As they were found to be treatment resistant, they weretaken up for the study. Patients having comorbidity of affective disorders, substance use disorders or organic dysfunction were excluded from the study. After taking informed consent, the history was recorded as per the specially prepared proforma. Baseline investigations viz. complete haemogram, chest X-ray, SGOT, SGPT, ECG, serum creatinine and urine analysis were done before starting clozapine. The psychopathology, side-effect profile with the blood cell counts (TLC & DLC) and the dose of clozapine were recorded weekly. Brief Psychiatric Rating Scale (BPRS, Overall & Gorham,1962) was used to rate the psychopathology weekly. All the patients in this study were followed over a minimum period of three months to evaluate their improvement. Before the initiation of clozapine therapy a wash out period of 7 days was given to those patients who were on oral neuroleptics. Patients who were on a drug holiday or had relapsed after stopping neuroleptics were started on clozapine after doing the baseline investigations. The initial dose of clozapine was 25 mg/day which was increased to 100 mg/day by the end of two weeks. Then the doses were titrated accordingly with increments being made by 25-50 mg every week. The gradual titration was done to see the therapeutic response to the minimum dose of clozapine and/or »he presence of side effects with the maximum dose range being 425-525 mg/ day by the end of three months. The side effects were recorded weekly and the scores were calculated at the end of 3 months as the total percentage of patients exhibiting them. A watch was kept for a decrease in the leucocyte count below 3000/cu mm or in the granulocyte count below 1500/cu mm which would necessitate discontinuation of clozapine. The total BPRS scores were compared at the end of 1 and 3 months respectively from the baseline score with the help of the paired t-test and the percentage improvement in the BPRS score at the end of three months was noted. RESULTS The population under study consisted of 28 patients, with age ranging from 15 to 60 years and a mean age of 32.64±13.73 years. There were 13 males (46.43) and 15 females (53.57%). Most of the patients were from low or lower middle socio-economic class with poor educational background. TABLE 1 BPRS TOTAL SCORES Baseline After 1 month After 3 months MEAN 29.75 19.70 14.71 S.D. 9.49 8.10* 7.08 ** * Paired T value =4.34; d.f.=27; (p<0.005) ** Paired 'f value = 8.89 ; d.f.=27; (p<0.005) The BPRS scores when compared from baseline (29.75±9.49) showed improvement both at the e> d of one month (19.7±8.1) and three months J4.71±7.08), which was statistically significant. When the percentage improvement in the BPRS scores at the end of 3 months was assessed, it was found that of 28 patients, 14 337