Recent clinical studies have reported beneficial effects of risperidone and olanzapine in autism and other pervasive developmental disorders, 1, 2 but clozapine has received little attention. 3 We describe the effects of clozapine in an adult with autistic disorder accompanied by disruptive behaviour. EB, a 32-year-old man, was diagnosed with autism at the age of 2. Deficit of development of spoken language and profound mental retardation (IQ= 20) were observed, and managing temper tantrums, impulsive behaviour and self-and others-directed aggressiveness became impossible by the age of 18. The patient was admitted to hospital frequently for selfinflicted injuries and was repeatedly admitted to various institutions for harming his parents and destroying household items. Pharmacological mono-or multitherapy was unsatisfactory due to poor clinical efficacy and the emergence of extrapyramidal side effects, including severe dystonia. Drugs used for several months during the course of treatment included haloperidol (up to 50 mg/day), thioridazine (up to 600 mg/day) and clotiapine (40 mg/day), and diazepam (up to 15 mg/day) for several years.

At the time of initial observation, when he was 27, Clinical Global Impression (CGI) rating was 7 and clinician-rated Visual Analog Scale (VAS) scores were 95 for aggressiveness, 15 and 10 for social and eye contact, respectively, 82 for irritability and 12 for talkativeness. 2 Treatment with clozapine was initiated after routine ECG, EEG and blood tests, and was progressively increased, reaching the maintenance dose of 300 mg/day (100 mg at 8 am, 12 noon and 4 pm) within 6 weeks. Treatment continued throughout the 5-year period (age 27 to 32), during which time regular blood testing was done. Clinical improvement was evident after 2 months of therapy. After 5 years of therapy, the patient showed marked improvement of aggressiveness and social interaction, and VAS scores were 15 for aggressiveness, 40 and 55 for social and eye contact, respectively, 35 for irritability and 45 for talkativeness. His CGI score was 4. Extrapyramidal side effects, white blood cell count changes, significant sedation or delayed reaction time were not observed. Self-and others-directed aggressiveness and temper tantrums are no longer observed. The patient’s social skills, in terms of group interaction, meeting with unfamiliar people and simple monosyllabic dialog, have dramatically improved. Ritualistic behaviour is also moderately reduced (Yale–Brown obsessive–compulsive scale score was 11 compared with 17 before therapy).