Pimozide versus chlorpromazine in chronic schizophrenia: a 52 week double-blind study of maintenance therapy. Comparison of pimozide and chlorpromazine in acute schizophrenia. Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study. Clinical trial of pimozide. Token economy, pimozide and chronic schizophrenia. Pimozide versus Haloperidol in acute schizophrenia. A double blind controlled study. Pimozide in chronic schizophrenic outpatients. A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia. A double-blind comparison of pimozide and chlorpromazine in the maintenance care of chronic schizophrenic outpatients. Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia. Are there schizophrenics for whom drugs may be unnecessary or contraindicated? Clozapine versus chlorpromazine for the treatment of schizophrenia: preliminary results from a double-blind study. Penfluridol: a long acting oral antipsychotic drug. Pimozide (R6238) in chronic schizophrenia: double blind trial. The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia. The risks and benefits of clozapine versus chlorpromazine. The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol. Activity in chronic schizophrenic patients: comparison of pimozide with fluphenazine in a double blind trial. One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol. Study of penfluridol and chlorpromazine in the treatment of chronic schizophrenia. Intermittent pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia. Prophylactic effects of neuroleptics in symptom-free schizophrenics: roles of dopaminergic and noradrenergic blockers. Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine. Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison. A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, I. A comparative double blind trial of pimozide and fluphenazine in chronic schizophrenia. Efficacy of lithium in schizophrenia. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, II. Lithium and chlorpromazine in psychotic inpatients.
This study compared the effectiveness and safety of pimozide and chlorpromazine in the maintenance therapy of chronic schizophrenic outpatients. Forty-three patients were assigned in double-blind fashion to one of the drugs for the 52 week study. Both medication groups showed a general pattern of improvement over the course of the study, but there was no significant difference between the two groups. The results demonstrated the effectiveness and safety of pimozide in once daily administration. Previous research results showing the special utility of pimozide for the improvement of emotional withdrawal and social competence in schizophrenia were not replicated. A four week double-blind study comparing pimozide and chlorpromazine was designed to test the hypothesis that pimozide, a powerful dopamine receptor blocker, is more effective in the treatment of acute schizophrenia than chlorpromazine. Twenty patients, 13 males and 7 females ranging in age from 21 to 53 years (mean age 33 years) admitted to ST. Mary's Hospital with acute schizophrenia were placed on the study. They were treated on an individual titrated dosage of either chlorpromazine 300 mg to 2100 mg, or pimozide 10 to 70 mg. The results revealed that on the Brief Psychiatric Rating Scale, the chlorpromazine group significantly improved after one week, whereas the pimozide group showed no statistical improvement until the third week. By the end of the study no significant differences were apparent between the two groups. In the Clinical Global Impression Scale, a significant difference between the two groups was found at week 4 showing a greater improvement in the chlorpromazine group. In terms of adverse reactions, the chlorpromazine group had significantly fewer extrapyramidal symptoms than the pimozide group (Simpson and Angus Scale) and in addition 15 adverse reactions were noted for the pimozide group as compared with 8 for the chlorpromazine group. This study shows that chlorpromazine has an earlier onset of action than pimozide in the acute schizophrenic patient despite the fact that it has a weaker effect on the dopamine receptor than has pimozide. In view of this finding, the dopamine theory of schizophrenia should be critically re-examined. In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients. Pimozide and Chlorpromazine were compared in chronic schizophrenics for their therapeutic effectiveness and tolerance, for four-weeks in both cases and for twelve months for pimozide. The minimum and maximum doses were 1 mg to 4 mg single dose for pimozide and 100 to 200 mg thrice daily for chlorpromazine. No significant global differences between the range of therapeutic activity of the two regimens were observed. Slightly more improvement was observed in mood and motor activity with pimozide. Drowsiness and dizziness, and extrapyramidal effects were more prominent with clorpromazine. Other side effects were infrequent. A prolonged improvement in 8 pimozide patients was maintained with mainly weight gain. The advantages of pimozide in chronic unsocialized schizophrenics appear to rest on its single oral daily dose regime, minimal undersirable effects, its specific enhancement of social integration and absence of undersirable effect on mental and physical performance. Response to a token economy was assessed in male chronic schizophrenic in-patients who were given, in a double-blind cross-over trial, pimozide (up to 20 mg daily) or chlorpromazine )up to 1,000 mg daily), each for three months. After six months there was little change in the patients' mental state, but general ward behaviour and token-rewarded "target" behaviours improved significantly. There were no statistically significant between-drug differences, but the trend was that general ward behaviour, but not token-rewarded behaviour, improved more on pimozide. The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory. Thirty acutely hospitalized schizophrenic patients were treated under double blind condition with either haloperidol (40-60 mg/day) or pimozide (40-60 mg/day) for 30 days. Ten patients in the pimozide and eleven in the haloperidol group showed a very good or good clinical response. There were no definite differences of treatment results as assessed by the Global Clinical Impression. Both groups showed a statistically significant decrease of the global scores of the Brief Psychiatric Rating Scale (p less than 0.01). There was a significant decrease of affective bluntedness and anergia in the pimozide but not in the haloperidol group. Extrapyramidal side effects were more pronounced in patients on pimozide who therefore needed more anticholinergic drugs. There was no consistent correlation between drug serum levels and global scores or single factors of the BPRS in either treatment group. It is concluded that pimozide in dose ranges from 40-60 mg has powerful antipsychotic properties indistinguishable from those of haloperidol but exerts stronger extrapyramidal side effects. In a double blind placebo controlled clinical evaluation of maintenance therapy in chronic schizophrenic female outpatients, thiordazine in single daily doses not exceeding 375 mg./day for 6 months was shown to be effective maintenance treatment compared with PL, thereby establishing the sensitivity of the experiment. Pimozide was also shown to be effective in a single oral dose not exceeding 16 mg./day and comparable overall to the standard drug. The experimental design was based on the anticipated retrogression of PL treated subjects during the 6-month study period, which was reflected in 5 of 9 (56%) "treatment failures" in the PL group compared to 2 of 14 (14%) and 2 of 12 (17%) in the THI and PIM groups, respectively. In addition, in some instances improvement over baseline evaluations was noted in both drug groups, particularly on global impression. Though some items of the BPRS exhibited Drug: PL differences, the scale in general was felt to be rather insensitive for this kind of study. Social adjustment ratings on a special scale completed by the patients and families alike, were also found to be insensitive to treatment differences. Side effects most often seen with THI were sedation, EKG and liver function abnormalities. Headache and restlessness occurred most often with PIM. Extrapyramidal symptoms and insomnia were seen most often with PIM and PL equally. Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed. nan In a double blind trial, 28 male chronic schizophrenic in-patients received either pimozide, given once weekly, or fluphenazine decanoate, given mostly once fortnightly. There was no difference in relapse rates over nine months. However, three-quarters of the patients on pimozide who completed the trial developed at least mild tardive dyskinesia. All patients on pimozide lost weight, the average loss being 5.4 kg (12 lbs). Plasma pimozide levels suggested satisfactory drug compliance. Plasma prolactin levels confirmed that in the pimozide group there was fluctuating dopamine receptor antagonism, while in the fluphenazine group average plasma prolactin levels throughout most of the interval between injections were at the upper limit of normal. This study reports that there are schizophrenics who do relatively well long term without the routine or continuous use of antipsychotic medication. Specially selected young males undergoing an acute schizophrenic episode were followed, after hospitalization, for up to three years. While hospitalized they were assigned randomly to either placebo or chlorpromazine treatment. Many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations and better overall function in the community than patients who were given chlorpromazine while in the hospital. Factors related to post-hospital outcome were good premorbid history and short-lived paranoid characteristics. Considerations which may have an effect on the successful management of acute schizophrenic patients not on medication are mentioned. The findings underline the need for further study of how to utilize antipsychotic medication more selectively in the treatment of schizophrenia. Fifteen schizophrenic inpatients were treated in a double-blind comparison study of clozapine versus chlorpromazine. Clozapine appeared to be at least as effective as chlorpromazine without producing any extrapyramidal reactions. Although bone marrow toxicity associated with clozapine has led to the drug's withdrawal from clinical use, data from studies of clozapine demonstrate that a drug can be effective antipsychotic without producing neurologic reactions. Penfluridol is a diphenylbutylpiperdine derivative with a half-life of sixty-six (66) hours. The present study was designed to determine its efficacy for the maintenance of schizophrenia. In a 52 week double-blind study, once weekly doses of penfluridol were compared with once daily doses of chlorpromazine in 56 schizophrenic patients receiving maintenance treatment on an outpatient basis. Both drugs were similar in their clinical effectiveness; no major side effects occurred with either drug. nan 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. 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). Pimozide and haloperidol were found to be equally effective in the treatment of acute schizophrenia in a double-blind clinical trial involving 22 patients. Drug plasma levels measured by radioimmunoassay (RIA) did not correlate with clinical response following either drug. Nor was there any correlation between clinical response and the dopamine receptor blocking activity of either drug as measured by radio receptor assay (RRA). Following pimozide plasma prolactin (PRL) levels correlated with clinical change, although the time courses of response of PRL and clinical response were dissimilar. There was no correlation between PRL and clinical response to haloperidol. RRA and RIA values correlated highly following pimozide but not haloperidol. Our findings lead us to conclude that the RRA technique reflects the plasma level of a drug rather than its central dopamine blocking activity. We also consider that the clinical response to antipsychotic drugs in schizophrenia may be less directly linked to dopamine receptor blockade than has previously been supposed. A double-blind crossover trial was carried out comparing pimozide with fluphenazine. The effects of the drugs on the activity of 20 chronic inert male schizophrenic patients were measured using nursing observations, psychiatric rating, and an operant conditioning method. When activity was assessed in these different ways, no significant difference was found between the two drugs on any of the measures. It is concluded that pimozide does not effectively increase the activity in such patients. It is considered that the free operant conditioning method used was shown to be a useful measure for comparing therapy in chronic schizophrenic patients. Amisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage.
                Sixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed.
                There were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication.
                In chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction. This study presents data on the use of penfluridol, a once-a-week orally administered, antipsychotic agent, in the treatment of chronic schizophrenic patients. Fifty-nine patients participated in the initial dose titration segment during which doses of penfluridol were adjusted weekly until the patients' condition became stabilized. The starting dose did not exceed 60 mg per week, and the maximum weekly dose did not exceed 140 mg. Forty-one of these patients continued on to participate in a double-blind comparison of penfluridol with chlorpromazine. Maximum doses did not exceed 140 mg per dose per week for penfluridol and 7350 mg per week for chlorpromazine in the double-blind segment. Patients were abruptly switched from their previous neuroleptic medication to penfluridol without loss of control. Side effects, mainly extrapyramidal in nature, were readily alleviated with benztropine mesylate. Penfluridol, administered orally once a week, appeared to be well tolerated; it was comparable to daily chlorpromazine in treating and maintaining schizophrenic patients. In a double-blind trial, 34 male chronic schizophrenic day-patients or in-patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide, given on four days each week. Over nine months relapse rates were similar for both groups, and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia. Plasma pimozide levels suggested satisfactory drug compliance. Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine. A clinical trial was undertaken to determine the role of dopaminergic and noradrenergic blockers in the maintenance treatment of remitted schizophrenics. One hundred and six remitted schizophrenic outpatients were treated with one of nine treatments, viz., thioridazine 25 mg or 75 mg, pimozide 2 mg or 6 mg, and their respective combinations, for 1 year in a double-blind controlled study employing a randomized design. The data from a previous study were utilized as a retrospective placebo group. Pimozide prolonged the number of symptom-free days in a dose-dependent manner and did so more markedly than thioridazine. Combined administration of pimozide and thioridazine prolonged the number of symptom-free days to a greater extent than their single administration. However, an inverted U-shaped dose-response curve was obtained with the combined administration of these agents. These data suggest that both the dopaminergic and noradrenergic blocking action of neuroleptics are important in preventing relapse in remitted schizophrenics. The purported advantages of second-generation or "atypical" antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia. This flexible-dose study examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia. In all, 160 inpatients with first-episode schizophrenia or schizophreniform disorder were randomized to CPZ or CLZ and followed them for 52 weeks or until dropout. The primary efficacy measure was time to first remission and proportion of time remaining in remission. The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects. Of these first-episode patients, 80% achieved remission within 1 year (79% CPZ, 81% CLZ). The Kaplan-Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ (chi(2)(1)=5.56, p=0.02). Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group. At 12 weeks, CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any. These symptom differences remained significant when controlling for EPS differences. By 52 weeks many of the symptom differences between groups were no longer significantly different. Generally, CLZ produced fewer side effects than CPZ, particularly extrapyramidal side effects. There was no significant difference between treatments in weight change or glucose metabolism. For each prior year of untreated psychosis, there was a 15% decrease in the odds of achieving remission (OR=0.85; CI 0.75-0.95). A high proportion of first-episode patients remitted within 1 year. We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission. However, first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ. While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks, the two treatment groups seemed to converge by 1 year. Longer duration of untreated psychosis was associated with lower odds of achieving remission. Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed. nan nan 60 Schizophrenic patients were given LiCo(3)/Chlorpromazine for 4 weeks, in a double blind cross over study with two placebo crossovers of 1 week before and two weeks after active treatment. Several core schizophrenic features showed significant reduction in severity with lithium. However, CPZ treatment was superior in terms of improvement, as compared to the other group on MBPRS and CGIS. Target symptoms may be one situation, where lithium could be tried and these results are discussed. The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics. DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 +/- 14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the double-blind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included "negative" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients. nan A sample of recently hospitalized psychotic patients was assigned to treatment with lithium or chlorpromazine in a double-blind drug trial. Several diagnostic systems were used to characterize the patients. No relationship was found, regardless of criterion system used, between diagnosis and differences in drug effectiveness; specifically, the presence of "schizophrenic" symptoms did not predict a poor response to lithium. Among patients with physical overactivity, those treated with lithium terminated earlier and had poorer outcome than those treated with chlorpromazine. In patients who were not overactive, the two drugs were equally effective, and chronically psychotic patients had poorer outcomes regardless of drug. Lithium may be an effective treatment for acutely psychotic patients who are not overactive. The use of a lithium trial as a diagnostic tool may be unwarranted.
Although there are shortcomings in the data, there is enough overall consistency over different outcomes and time scales to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. There are no data to support or refute its use for those with delusional disorder.