A double-blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia. The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia. Multicenter study comparing thioridazine with diazepam and placebo in elderly, nonpsychotic patients with emotional and behavioral disorders. Remoxipride versus thioridazine in elderly psychotic patients. The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia. Comparison of SCH-12679 and thioridazine in aggressive mental retardates. [Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness]. The risks and benefits of clozapine versus chlorpromazine. Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.
Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests. A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects. Thioridazine was compared with placebo or diazepam or both in 610 elderly, nonpsychotic inpatients in geriatric wards of state hospitals or nursing homes. All patients manifested disruptive and difficult-to-manage behavior that interfered with adjustment to their environment and with proper care and treatment of their medical and emotional problems. Target symptoms such as agitation, anxiety, tension, apprehension, depressed mood, and sleep disturbances showed consistently marked improvement throughout the four-week study, as measured by the modified Hamilton Anxiety Scale, the modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and global ratings. Significantly greater improvement on all measures was achieved with thioridazine than with placebo. In addition, greater improvement in the majority of symptoms assessed by the Hamilton Anxiety Scale and NOSIE were seen in patients who received thioridazine than in those given diazepam. A total of 18 hospitalized elderly psychotic patients in need of antipsychotic treatment took part in a double-blind exploratory study concerning the safety, tolerability and efficacy of remoxipride and thioridazine. Their median age was 78 years (range 66-90 years). Over the study period of 6 weeks, 9 patients received remoxipride and 9 thioridazine. Both drugs were given in a dosage range of 50-200 mg/day. The median total score on the Brief Psychiatric Rating Scale at the start of active treatment was 18 in the remoxipride group and 24 in the thioridazine group. The scores were reduced to 6 and 7, respectively, at the last rating. The Clinical Global Impression at last rating showed 4 of the 9 remoxipride patients to be very much improved compared to 1 of the 9 thioridazine patients. Apart from three reports of severe drowsiness in the thioridazine group, the incidence of treatment-emergent adverse effects was low in both groups. No clinically significant aberrations were seen in laboratory tests or cardiovascular data. In conclusion, remoxipride seemed to be well tolerated in this group of patients and its antipsychotic efficacy in the doses used is promising. There has been an absence of controlled studies focusing specifically on neuroleptic treatment in the elderly schizophrenic population. Therefore, we conducted a 12-week double-blind comparison study to assess the efficacy and tolerability of clozapine and chlorpromazine in a group of elderly inpatients with chronic schizophrenia.
                Forty-two elderly DSM-IV schizophrenic veterans were randomly assigned to clozapine or chlorpromazine and assessed for efficacy at baseline and at termination with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions scale (CGI). Side effects were also monitored. Medications were titrated, on the basis of clinical response and side effects, to a maximum dose of 300 mg/day of clozapine or 600 mg/day of chlorpromazine.
                The results suggest that both the chlorpromazine and clozapine groups improved their PANSS scores at termination compared with baseline, but the difference between the 2 groups was not statistically significant. The mean CGI scores reflecting severity of illness also demonstrated improvement in both groups over time. Both groups had similar incidences of side effects. One patient in each group had a life-threatening side effect. More patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients noted sedation.
                We concluded that both clozapine and chlorpromazine are effective treatments for psychosis and behavioral disturbances in geriatric schizophrenia. Both agents had similar incidences of side effects. With careful monitoring and titration of dosage, both clozapine and chlorpromazine were fairly well tolerated in this population. 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. The dibenzothiepine zotepine is a new potential "atypical" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment. Clozapine is an atypical antipsychotic drug with reduced risk of unwanted neurological effects in comparison with other drugs. In this multicenter study, 151 hospitalized schizophrenic patients were randomly assigned to treatment under double-blind conditions to assess the antipsychotic efficacy and safety of clozapine versus chlorpromazine. All patients exhibited tardive dyskinesia or other extrapyramidal side effects associated with at least two prior neuroleptics. Eleven patients were dropped from treatment due to extrapyramidal symptoms while being treated with chlorpromazine; only one clozapine patient's treatment was terminated for this reason. Clozapine patients exhibited clinical improvement superior to that of chlorpromazine patients as assessed by the Brief Psychiatric Rating and Clinical Global Impression scales. These results suggest that clozapine is well tolerated and may be therapeutically superior to chlorpromazine in treating psychotic behavior. Agranulocytosis potential can be minimized by frequent white blood cell counts and removing nonresponding patients from treatment prior to the peak risk period (months 2 through 6). To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.
                Prospective, randomized, double-blind clinical trial.
                25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.
                Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.
                These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.
Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified.