Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Haloperidol in schizophrenic children: early findings from a study in progress. Parenteral haloperidol for rapid control of severe, disruptive symptoms of acute schizophrenia. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Haloperidol: a controlled trial in chronic schizophrenia. Risperidone in the treatment of schizophrenia. Prophylactic effect of neuroleptics in symptom-free schizophrenics. Experimental examination of trazodone. Efficacy and safety of tiospirone vs. haloperidol and thioridazine in a double-blind, placebo-controlled trial. Prophylactic effect of neuroleptics in symptom-free schizophrenics: a comparative dose-response study of haloperidol and propericiazine. Loxapine succinate: a double-blind comparison with haloperidol and placebo in acute schizophrenics. Plasma alpha-one acid glycoprotein and haloperidol concentrations in schizophrenic patients. Risperidone: clinical safety and efficacy in schizophrenia. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial.
Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day. This report presents preliminary findings in an ongoing double-blind, placebo-controlled study of the safety and efficacy of haloperidol in hospitalized schizophrenic children. The subjects are diagnosed schizophrenic by DSM-III-R criteria and admitted to the Bellevue Hospital Children's Inpatient Psychiatric Unit. The study is 10 weeks in duration and employs a crossover design. After a 2-week placebo baseline period, the subjects enter double-blind treatment for 8 weeks, by random assignment receiving either haloperidol for 4 weeks followed by placebo for 4 weeks, or alternatively, placebo for 4 weeks followed by haloperidol for 4 weeks. Dosage, regulated individually, ranges from 0.5 to 10.0 mg/day. To date, of an anticipated 20 subjects, 12 have completed the study. These children, 9 boys and 3 girls, were ages 5.5 to 11.75 years upon study entry. Haloperidol was superior to placebo for reduction of target symptoms with optimal haloperidol dose of 0.5 to 3.5 mg/day (0.02-0.12 mg/kg/day). Intramuscular haloperidol, at three dose levels, (5 mg, 2 mg, and 1 mg) chlorpromazine (25 mg), and placebo were compared for efficacy, rapidity of therapeutic onset, and safety in 50 acute psychotic patients requiring rapid control. The drugs were administered parenterally under double-blind conditions at half-hour intervals until successful control of moderate to very severe symptomatology was achieved or a maximum of four injections had been given. Global evaluation, BPRS, and target symptom ratings were performed. The overall results indicated that the 5 mg and 2 mg haloperidol doses were significantly superior to the 1 mg haloperidol and 25 mg chlorpromazine doses and to placebo. Transfer of patients to oral haloperidol was satisfactorily accomplished. Side effects for all medications were minimal and included slight to moderate EPS and drowsiness. The use of antiparkinson drugs completely controlled the extrapyramidal symptoms. Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo.
                A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval.
                Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval.
                Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder. In a double-blind study, 135 inpatients with a diagnosis of chronic schizophrenia were randomly assigned to 8 weeks of treatment with one of six parallel treatments: risperidone (a new central 5-hydroxytryptamine2 and dopamine D2 antagonist), 2, 6, 10, 16 mg/day; haloperidol, 20 mg/day; or placebo, after a single-blind placebo washout period. Doses were increased in fixed increments up to a fixed maintenance dose reached after 1 week. On the Clinical Global Impression-Severity of Illness and Improvement, all active medications were superior to placebo except for risperidone (2 mg) on the Clinical Global Impression-Improvement. On the total Positive and Negative Syndrome Scale (PANSS) score and positive subscale, superiority to placebo was observed for all treatment groups except for haloperidol and risperidone (2 mg), which tended to be superior to placebo on total PANSS and the positive subscale, respectively. On the PANSS negative subscale, only risperidone (6 mg/day) was significantly better than placebo. Risperidone (6 mg) was superior to haloperidol on the total PANSS, General Psychopathology, and Brief Psychiatric Rating Scale subscales. Although there was a linear increase in parkinsonism with increasing risperidone dosage, there were no statistically significant differences between risperidone (2, 6, and 16 mg/day) and placebo. At doses of 6 to 16 mg, risperidone displayed a marked antidyskinetic effect compared with placebo. This effect was more pronounced in patients with severe dyskinesia. By contrast, haloperidol produced significantly more parkinsonism than placebo and risperidone (2, 6 and 16 mg), with no effect on tardive dyskinesia. These data suggest that risperidone, at the optimal therapeutic dose of 6 mg/day, produced significant improvement in both positive and negative symptoms without an increase in drug-induced parkinsonian symptoms and with a significant beneficial effect on tardive dyskinesia. nan The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose.
                This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States. Patients were randomly assigned to 8 weeks' treatment with placebo, one of four doses of risperidone (2, 6, 10, or 16 mg), or 20 mg of haloperidol daily.
                Clinical improvement (20% reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% of the patients receiving 2 mg of risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg; and by 30% receiving haloperidol and 22% receiving placebo. Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol. Positive symptom scores were significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of haloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 16 mg of risperidone. The incidence of extra-pyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo. The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 16 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo.
                Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia. Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the "first assigned drugs" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics. To establish the differential indication of trazodone and to find the predictors of its efficacy, we conducted a study in which 45 patients with major depressive disorder and 75 patients with acute schizophrenia were randomly assigned under double-blind conditions to either 400 mg trazodone daily, 150 mg amitriptyline daily, 20 mg haloperidol daily, or placebo daily. At the beginning of the investigations, numerous variables (basic data, MMPI, AMDP, HAM-A, HAM-D) were documented and evaluated on days 3, 7, 14, and 21. In our study, trazodone proved to be as effective an antidepressant drug as amitriptyline. In group comparison, no antipsychotic action of trazodone in schizophrenic patients could be proved. Yet the trazodone treatment was clearly of less risk than the amitriptyline treatment. Under trazodone, provocation of schizophrenic symptoms, which occurred numerously under amitriptyline, was found only in one patient out of 17 schizophrenics. Related to anamnesis and characteristics of the schizophrenic patient, a predictor-variable concerning the antipsychotic effect was not found. It can be assured, however, that patients with depressive symptoms (regarding the entity classification) respond to trazodone. After only 7 days of trazodone treatment, a relatively reliable decision can be established as to whether a therapeutical success can be expected if treatment is continued. nan Remitted schizophrenic outpatients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a randomized design. The drug's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared. Patients were randomly assigned to the following drugs orally administered once per day at night: placebo; haloperidol 1 mg, 3 mg, and 6 mg; propericiazine 10 mg, 30 mg, and 60 mg. Serum prolactin levels in each patient were estimated by radioimmunoassay. All patients treated with placebo relapsed within 1 year and the relapse rate with placebo was significantly higher than with any dose of the two neuroleptics. Haloperidol increased the number of symptom-free days in a dose-dependent manner. Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg, the number decreased. It appears that propericiazine shows an inverted U-shaped dose-response curve. Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days. The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider "therapeutic window" in maintenance treatment and antidopaminergic properties of neuroleptics, wherein it is important to prevent relapse even in remitted schizophrenics. nan Thirty six schizophrenic patients were randomly assigned to placebo or haloperidol treatment for 6 weeks. Blood samples to measure plasma alpha-one acid glycoprotein (AAG), haloperidol and reduced haloperidol concentrations were obtained at baseline and weeks 2, 4, and 6. Blood samples were obtained 10-12 h after the evening dose and prior to the morning dose. Haloperidol and reduced haloperidol was assayed by HPLC with electrochemical detection. Plasma AAG levels were assayed by radial immunodiffusion. Patients were clinically assessed by the Brief Psychiatric Rating Scale (BPRS) and Abnormal Involuntary Movement Scale at baseline and weeks 2, 4, and 6. BPRS scores did not significantly decrease during placebo treatment, although a slight drop in plasma AAG levels was found. Haloperidol produced a significant decrease in BPRS scores and plasma AAG levels. Mean plasma haloperidol levels were 12.9 +/- 14.7 ng/ml at week 6. Significant correlations between decreasing BPRS scores and plasma AAG levels were not found with only a strong trend at week 2 (r = 0.445, p = 0.073). The role of AAG and psychotropic drug disposition in psychiatric patients requires further evaluation. Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol. Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.