Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. The Eltoprazine Aggression Research Group. Pipamperone (Dipiperon, R3345) in troublesome mental retardates: a double-blind placebo controlled cross-over study with long-term follow-up. A controlled trial of prothipendyl (tolnate) in mentally subnormal patients. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. The effect of milenperone on the aggressive behavior of oligophrenic patients. A double-blind placebo-controlled study. Penfluridol (R 16341). A long-acting oral neuroleptic, as maintenance therapy for schizophrenic and mentally retarded patients. A placebo-controlled double-blind trial. Pipothiazine palmitate in the management of aggressive mentally handicapped patients. Comparison of SCH-12679 and thioridazine in aggressive mental retardates.
The efficacy of eltoprazine, a mixed 5-HT1 agonist, in treating aggressive behaviour in mentally handicapped patients was evaluated in a double-blind, placebo- and baseline-controlled study. In the total sample of 160 patients who entered the 8 week double-blind treatment phase, efficacy was not demonstrated. Also in a 28 week double-blind follow-up study, efficacy could not be demonstrated. Post-hoc exploratory analyses suggested eltoprazine was significantly better than placebo in reducing aggression scores of a subgroup of severely aggressive patients. There was no evident relationship between the plasma level of eltoprazine and therapeutic effect or safety and tolerance. The overall safety and tolerance of chronic eltoprazine treatment was good. In the discussion, several issues and pitfalls of aggression research are dealt with. A 6-week double-blind cross-over study comparing pipamperone with placebo was conducted in 20 female mental retardates with behavioural disorders. The ages of the patients ranged between 22 and 42 years. After a 2-week washout period, patients were randomly allocated to either pipamperone or placebo treatment. The initial dosage of pipamperone was 40 mg b.i.d., which was gradually increased to 80 mg b.i.d. within 5 days. Patients were assessed using a ten-item rating scale before and after each week of treatment. For six of the ten items, patients showed a better response during the pipamperone than during the placebo period. When pre-trial scores were compared with those at the end of the trial, seven items had significantly improved with pipamperone. The nursing staff considered the patients more alert and amenable during pipamperone treatment. nan Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism.
                Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone.
                For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures.
                Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults. The antiaggressive action and the side effects of a new neuroleptic, milenperone, were evaluated in 21 oligophrenic patients by means of a double-blind randomized pilot study in comparison with placebo. Only 3 patients appeared to be psychotic, 2 from the milenperone group and 1 from the placebo group. In this study, milenperone was added to the existing psychotropic medication as an adjuvant. The test substance was administered in a dose of 2 X 10 mg daily for 6 weeks. The results were evaluated by means of the Paranoid Belligerence Scale and the improvement of the target symptoms were visualized on the Visual Analogue Line. Although, in the last 3 weeks of the study, the aggressiveness scores had decreased more in the milenperone group than in the placebo group, the difference between both studied groups was not significant. This lack of clear result may probably be ascribed to the high standard deviations, together with the small number of patients per group. The severity and frequency of the side effects remained almost unchanged during the investigation and were independent of the substance administered: milenperone or placebo. nan The efficacy of intramuscular pipothiazine palmitate (PP) in the management of aggressive mentally handicapped patients was examined in a double-blind, placebo-controlled, cross-over study, in which 30 patients received each treatment for 13 weeks. A target symptom scale of aggressiveness (TSA) and a clinical global impression scale of efficacy were rated at monthly intervals, and an extra-pyramidal side-effects scale weekly. The patients showed marked improvement during treatment with PP, which was assessed as superior to placebo. Individual and total TSA scores were also reduced compared to placebo. SCH-12679, a benzazepine derivative, was compared to thioridazine and to placebo on the aggressive behaviour of mentally retarded patients. After a three-week chlorpromazine (100 mg t.i.d.) standardizaton period, no significant differences between the three treatment groups were observed in their abnormal behaviour. During the comparative phase, patients treated with SCH-12679 became less hyperative and less agitated while those treated with thioridazine became more violent, more choleric and more provocative. The clinical investigator and the nursing staff found significant differences between the active drugs. As compared to the placebo, SCH-12679 improved the behaviour of the patients while thioridazine aggravated their condition. No important adverse reaction was found and the drugs did not interact with the sex of the patients and the presence of epilepsy. The results suggest that, in mental retardation, physical restraint of hyperactivity might induce aggressivity and that one should be cautious in using neuroleptics in nonpsychotic patients.
There are limited data on this important issue and more research is urgently needed.