The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol. Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study. A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, II. Pimozide (R6238) in chronic schizophrenia: double blind trial. A double-blind comparison of pimozide vs. trifluoperazine in schizophrenic outpatients. A three-year double-blind investigation of pimozide versus fluphenazine in chronic schizophrenia. Comparison of pimozide and chlorpromazine in acute schizophrenia. A double-blind comparison of once-a-day pimozide, trifluoperazine, and placebo in the maintenance care of chronic schizophrenic outpatients. The observer interaction variable in evaluation of socialising properties of pimozide (Orap). A double-blind comparison of pimozide with carpipramine in schizophrenic patients. Use of the Social Behaviour Assessment Schedule (SBAS) in a trial of maintenance antipsychotic therapy in schizophrenic outpatients: pimozide versus fluphenazine. Weekly pimozide versus fluphenazine decanoate in schizophrenic out-and day-patients. [Pimozide and piportil in the treatment of chronic schizophrenia (preliminary communication)]. Pimozide versus Haloperidol in acute schizophrenia. A double blind controlled study. A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia. Prophylactic effects of neuroleptics in symptom-free schizophrenics: roles of dopaminergic and noradrenergic blockers. Activity in chronic schizophrenic patients: comparison of pimozide with fluphenazine in a double blind trial. Token economy, pimozide and chronic schizophrenia. Pimozide in chronic schizophrenic patients. A controlled trial of pimozide and trifluoperazine in chronic schizophrenic syndromes. Pimozide in chronic schizophrenic outpatients. Pimozide versus chlorpromazine in chronic schizophrenia: a 52 week double-blind study of maintenance therapy. Pimozide (orap, R 6238) in residual schizophrenia. A clinical evaluation with long-term double-blind follow-up. The Scottish first episode schizophrenia study. VII. Two-year follow-up. Scottish Schizophrenia Research Group. Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia. A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, I. Intermittent pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia. A double-blind comparison of pimozide and chlorpromazine in the maintenance care of chronic schizophrenic outpatients. A comparative double blind trial of pimozide and fluphenazine in chronic schizophrenia. Clinical trial of pimozide.
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. 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. nan nan nan nan 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. nan Eighteen chronic, institutionalised patients were randomly assigned to two groups for the purpose of a double blind trial of pimozide (Orap). The results of the study indicated an increase in socialisation, as measured by the Venables scale, for both groups, and no significant difference in this variable between placebo and active preparation groups. It is suggested that greater observer interaction may be responsible for the observed increase in socialisation previously attributed to pimozide. nan nan nan nan 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. 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. 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. 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. 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. nan nan 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. 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. nan Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms. 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. nan 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. nan nan 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.
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.