To the Editor: Information about the efficacy of atypical antipsychotics in community care settings is limited. Through the Greater Vancouver Mental Health Service Society (1), we conducted an open-label trial of olanzapine with consecutive patients started on the drug during a six-month period in 1996-1997.
Severity of illness was rated on the 7-point Clinical Global Impression of illness severity scale (CGI) (2); the ratings range from 1, indicating that a patient is free of illness, to 7, indicating an extreme degree of illness. Ratings of functioning were made using the 100-point Social and Occupational Functioning Scale (SOFAS) (3); ratings on this scale range from 20, indicating that the patient is unable to function independently, to 90, indicating that the patient is functioning well in all areas. Side effects of olanzapine were noted.
Ratings were taken at baseline and at four, eight, and 12 weeks after entry into the study. Reasons for discontinuation and changes in dyskinetic movements were noted in narratives. Flexible dosing was used. The study proceeded with the approval of the university's ethics review board.
Forty-two patients, 20 males and 22 females, with a mean±SD age of 41±14.3 years (range, 16 to 24) participated in the study. Their mean duration of illness was 14.8±9.9 years (range, 1 to 40). Thirty-two had a DSM-IV diagnosis of schizophrenia, four of schizoaffective disorder, and six of nonschizophrenic psychosis.
Subjects were offered olanzapine if they had suboptimal response or intolerance to their baseline treatment with typical antipsychotics (N=13), depot antipsychotics (N=6), risperidone (N=17), or clozapine (N=5) or had not previously been prescribed an antipsychotic drug (N=1).
The mean±SD baseline score on the CGI was 4.4±1.1 (range, 2 to 6); on the SOFAS it was 50±13 (range, 30 to 70). Paired t tests were used to determine whether there were significant differences between scores at the various follow-up points. Responders were categorized as those who improved at least one point on the CGI and at least one category on the SOFAS.
At 12 weeks the mean CGI score was 3.4±1.6 (range, 1 to 6), a significant improvement from baseline (t=4.3, df=35, p=.001). The SOFAS mean score was 59.4±15.7 (range, 35 to 90), also a significant improvement (t=-3.9, df=35, p=.005).
Eleven subjects (26 percent) responded to olanzapine by four weeks, 14 (33 percent) by eight weeks, and 15 (37 percent) by 12 weeks. Seven subjects (17 percent) improved dramatically; one subject had previously received a typical antipsychotic, one a depot antipsychotic, three risperidone, and two clozapine.
The mean±SD dose of olanzapine at 12 weeks was 12.8±6.54 mg per day (range, 2.5 to 35 mg). Side effects were noted in 16 of the 42 subjects (38 percent). Four experienced akathisia, four sedation, and two weight gain; one each reported blurred vision, constipation, worsening of congestive heart failure, difficulty concentrating, and arm pain. One subject had both insomnia and a rash.
At baseline, clinically significant tardive dyskinesia was observed in four subjects. By 12 weeks, one subject had improved, and tardive dyskinesia had disappeared in the other three. Improvement in dyskinesia may represent resolution of extrapyramidal side effects or, as is the case with other atypical antipsychotics (4), may reflect an intrinsic antidyskinetic activity.
Six subjects (14 percent) dropped out of the trial, two because of worsening psychosis, two because of no improvement, one because of difficulty concentrating, and one because of lack of insight.
The study was limited in that neither clinicians nor patients were blind to the drug being prescribed, and no direct comparison was made to another treatment. However, in this cohort of community mental health patients, olanzapine appears to hold promise as an effective and well-tolerated antipsychotic.
The authors are with the department of psychiatry at the University of British Columbia Faculty of Medicine in Vancouver. Drs. Sladen-Dew and Altman are also associated with the Greater Vancouver Mental Health Services Society.