The aim of the present study was to evaluate the short-term efficacy and safety of risperidone in a group of Asian patients with schizophrenia who were treated at Woodbridge Hospital in Singapore.

Before commencing on risperidone, all the patients underwent a 1-week washout period of oral medications. Patients receiving depot antipsychotics were started on risperidone at the midpoint of the week that they would have received their next injection. Antiparkinsonian medications were continued during the washout period; however, they were adjusted or stopped during the trial, depending on each patient’s symptoms.

The risperidone dose was titrated, up to a daily dose of 4 mg at day 14, and thereafter adjusted according to the patient’s clinical response.

Symptoms were rated at baseline and at 1, 2, 4, 6, and 8 weeks of risperidone treatment. Haematological and blood chemistry (urea/electrolytes, serum creatinine, and liver enzymes) tests were performed at baseline and at study end point. Other adverse reactions were evaluated by patient query and observation by the study psychiatrists.

Measured values are expressed as means w SD (standard deviation). Characteristics and clinical ratings were compared using Wilcoxon’s signed rank test.

Of the 20 patients who completed the 8-week trial, 16 were Chinese, 2 were Malays, and 2 were Indians (Table I). The schizophrenia subtypes included disorganised (7 patients), undifferentiated (5 patients), paranoid (6 patients), and residual (2 patients). The patients’ mean age was 34.8 w 8.8 years

(range, 19 to 53). The mean duration of illness was 10.6 w 7.3 years (range, 2 to 30), with a mean age of onset at 24.3 w 7.6 years (range, 11 to 45). Fourteen patients had been receiving depot medication prior to the study. The mean end point risperidone dose was 5.6 mg/day (range, 3 to 8 mg/day).

Efficacy

Reductions in scores from baseline to end point were noted in all but 1 of the 30 individual PANSS items (mannerisms and posturing: 1.0 at baseline, 1.2 at end point; not significant). Items that showed a significant reduction are shown in Table II; they include 4 of the 7 positive symptoms, 4 of the 7 negative symptoms, and 6 of the 16 symptoms of general psychopathology.

Clinical global impression scores indicated that 17 (85%) out of 20 patients improved at end point: 2 (10%) were very much improved, 10 (50%) much improved, and 5 (25%) minimally improved, and 3 (15%) were unchanged.

Severity of EPS was significantly reduced during treatment: mean total ESRS scores were 9.4 w 9.3 at baseline and 5.4 w 3.2 at end point (p l 0.05) (Table I). ESRS scores were reduced in 12 out of 20 patients, were unchanged in 3, and increased in 5.

Sixteen out of 20 patients were receiving anti-parkinsonian medication (trihexyphenidyl) before the trial, compared with 12 patients at end point. Although the mean dose of trihexyphenidyl was lower at the end of the trial (2.5 w 2.7 mg/day versus 3.8 w 2.4 mg/day at baseline), the reduction was not statistically significant.

Other adverse events reported include giddiness in three patients, headache in two, and agitation in another two patients. One female patient reported galactorrhea and another developed obsessive-compulsive symptoms. No haematological abnormalities were detected at the end of the trial.

The 85% response rate of the patients in the present study is greater than that found in the North American trial (61% at a fixed dose of 6 mg/day of risperidone)(1,2) or in the multinational study (63% at 4 mg/day and 66% at 8 mg/day of risperidone)(3). In these studies, there is good agreement that the daily risperidone dose of 4 to 8 mg is optimal. The mean dose of our responders (5.6 mg/day) fell within this range.

Although the total mean ESRS score was significantly lower at end point than at baseline, 60% (12 of 20) still required antiparkinsonian medication. Because the washout period was rather short and most of the patients were receiving depot antipsychotic treatment before the trial, residual antipsychotic effects may have contributed to increased EPS and possibly made the patients more sensitive to EPS. Another factor may be ethnic differences. Asian patients have been shown to be more sensitive to haloperidol-induced EPS(10). It has been suggested that Asians are more sensitive to the dopaminergic blockade of antipsychotics and may require low doses of risperidone(11).

The role of risperidone in treatment-refractory schizophrenia is yet to be established. The characteristics of our sample - mean age of 34 years, duration of illness more than 10 years, and 7 prior hospitalisations - suggest that many poor or partial responders to conventional antipsychotics were included in the study. This suggests that risperidone may be effective in treatment-refractory schizophrenia.

The study has a number of limitations, including the small sample size, the lack of a placebo and active drug control group, and the open design that could have inflated the response rate. The clinical status of the patients also did not permit an adequate period of washout for those who had been on depot antipsychotics. Nonetheless, the findings suggest that risperidone is effective and well tolerated in Asian patients with schizophrenia.

We would like to thank Dr Teo Seng Hock for his support, Mr Lim Tim Poh and the nursing staff for their assistance.

S A Chong, MBBS,
MMed (Psych)
Senior Registrar

H L Yap, MBBS, MMed (Psych)
Consultant

B L Low, MBBS, MMed (Psych)
Consultant

C H Choo, MBBS,
MMed (Psych)
Senior Registrar