timiperone and Schizophrenia

Remitted schizophrenic outpatients were prophylactically treated to prevent relapse with three different doses of timiperone or sulpiride for a year in a double-blind controlled study employing a randomized design. Each drug's ability to prevent relapse was by counting the number of subjects with different outcomes (remission, relapse, adverse reactions) during the trial and/or the number of symptom-free days for each patient before any sign of relapse or adverse reactions appeared. Patients were randomly assigned to the following drugs, which were orally administered once every night: placebo; timiperone 1 mg, 3 mg, 6 mg; sulpiride 100 mg, 300 mg, 600 mg. Data from previous studies involving haloperidol and propericiazine were utilized as a retrospective placebo group to compare the characteristics of the four drugs for maintenance treatment of remitted schizophrenic outpatients. Both timiperone and sulpiride increased the number of patients in remission and decreased the number of patients who relapsed, compared with the placebo group. With timiperone, there was an especially marked increase in the number of patients who showed signs of adverse reactions compared with sulpiride. Sulpiride was the only drug that increased the number of dose-dependent symptom-free days. However, both of these drugs significantly increased the number of symptom-free days compared with placebo. By comparing the dose-response curves of four drugs tested in the same fashion, haloperidol and sulpiride were superior to propericiazine and timiperone because they displayed a wider dose range for the maintenance treatment of remitted schizophrenic outpatients.

Topics: Adult; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Random Allocation; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Sulpiride

The efficacy and safety of timiperone, a new butyrophenone derivative, in schizophrenia as compared with haloperidol were assessed in a multi-clinic double-blind controlled study in a total of 206 patients. The patients were given timiperone (1.0 mg/tablet) or haloperidol (1.5 mg/tablet) in a daily dose of 1--3 tablets for the first day, then up to a maximum of 12 tablets depending on symptoms for 12 weeks. Timiperone was found to be significantly superior to haloperidol in the final global improvement rating and in the general usefulness rating. In the over-all safety rating there were no statistically significant differences between the two drug treatments. With regard to analysis by stratification timiperone was superior to haloperidol in improving abnormal experiences such as hallucination and delusion as well as deficiency of initiative and blunted affect. From these results it is considered that timiperone could be superior to haloperidol in the treatment of schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Schizophrenia

The clinical efficacy and safety of timiperone, a new butyrophenone derivative, on chronic schizophrenia was compared with clocapramine by the double-blind method using a total of eighty-eight patients, consisting of forty-four patients in each group. In the final global improvement rating, the global improvement rating in each week and the general usefulness rating, there were no statistically significant differences between the two groups. However, in the global improvement rating in each symptom, timiperone was significantly superior to clocapramine in delusion and showed a superior tendency to clocapramine in contact. Timiperone showed a higher improvement rate than clocapramine in hallucination and disturbance of self-consciousness. In the over-all safety rating, there were no significant differences between the two groups, but in accompanying symptoms and side-effects, timiperone showed significantly less tendency than clocapramine in dyskinesia, insomnia, constipation and nausea. From these results, including the analysis by stratification, it was considered that timiperone was a superior or equivalent neuroleptic in comparison with clocapramine against the negative symptoms as well as the positive ones of chronic schizophrenia, and was equally safe or safer than clocapramine.

Topics: Adolescent; Adult; Antipsychotic Agents; Butyrophenones; Clinical Trials as Topic; Dibenzazepines; Double-Blind Method; Humans; Middle Aged; Schizophrenia; Tranquilizing Agents

The efficacy of timiperone in schizophrenia as compared with perphenazine was assessed in a double-blind fashion in 205 patients throughout a 12-week treatment period. More than half of the subjects were chronic schizophrenics. Global improvement in the timiperone treatment group was superior to that in the perphenazine group in view of a lower rate of aggravation. With regard to overall safety and general usefulness rating, there were no significant differences between the two drug treatments. However, timiperone showed less frequency of excitability, irritability, anxiety and anorexia than perphenazine on occasions during the 12 week treatment period. From these results it may be concluded that the efficacy of timiperone could be superior or equivalent to that of perphenazine which has been confirmed to be of use as an antipsychotic.

Topics: Adolescent; Adult; Antipsychotic Agents; Butyrophenones; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Middle Aged; Perphenazine; Schizophrenia; Schizophrenic Psychology

Plasma levels of timiperone (TIM) and reduced timiperone (RTIM) were determined in 10 schizophrenic patients who were treated with TIM. Activities of ketone reductase in red blood cells (RBC) were assayed using TIM and haloperidol (HAL) as substrates. Plasma levels of TIM and RTIM ranged from 3.2 ng/mL to 9.5 ng/mL and from 1.7 ng/mL to 7.6 ng/mL, respectively, and approximately four-fold inter-individual variations in RTIM/TIM (0.37-1.43, 0.67 +/- 0.25) were observed. There were significant and positive correlations between plasma levels of TIM or RTIM with the daily doses of TIM (mg/kg body weight); TIM (ng/mL)= 19.5 x daily dose of TIM (mg/kg) + 1.3, r = 0.79, n = 18, P < 0.01; RTIM (ng/mL) = 13.1 x daily dose of TIM (mg/kg) + 0.7, r = 0.73, n = 18, P < 0.001). Given 0.3 mg/kg of TIM, a plasma level of TIM as 7.15 ng/mL was predicted, which is approximately 60% that of HAL. The activity of TIM reductase in RBC was determined as approximately 70% of HAL reductase in RBC, although the correlation between the activities of TIM reductase and HAL reductase in RBC was high (r = 0.98, n = 10, P < 0.001).

Topics: Adolescent; Adult; Antipsychotic Agents; Butyrophenones; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Oxidation-Reduction; Schizophrenia; Structure-Activity Relationship