Study of penfluridol and chlorpromazine in the treatment of chronic schizophrenia. Loxapine versus chlorpromazine in paranoid schizophrenia: a double-blind study. Comparison of pimozide and chlorpromazine in acute schizophrenia. Propranolol as an adjunct to the treatment of schizophrenia. The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia. Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia. Role of ect phenothiazine combination in schizophrenia. Pimozide versus chlorpromazine in chronic schizophrenia: a 52 week double-blind study of maintenance therapy. High dosage haloperidol in chronic schizophrenia.
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. Newly admitted paranoid schizophrenic patients (N = 68) were treated with either loxapine or chlorpromazine for up to 4 weeks. Mean maximum dosages were 84 mg/day of loxapine and 820 mg/day of chlorpromazine. Loxapine showed efficacy superior to that of chlorpromazine, confirming earlier retrospective findings. Adverse reactions were also less troublesome with loxapine. 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. Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more. 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. The purpose of this study was to compare the efficacy of olanzapine with that of chlorpromazine plus benztropine in patients with treatment-resistant schizophrenia.
                One hundred three previously treatment-resistant patients with schizophrenia diagnosed according to the DSM-III-R criteria were given a prospective 6-week trial of 10-40 mg/day of haloperidol. Eighty-four of them failed to respond to that trial and agreed to be randomly assigned to an 8-week fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of chlorpromazine plus 4 mg/day of benztropine mesylate.
                Fifty-nine (70%) of the 84 subjects completed the trial. The primary outcome measures were Brief Psychiatric Rating Scale total score and positive symptom score, Scale for the Assessment of Negative Symptoms global score, and Clinical Global Impression score. An analysis of variance for the subjects who completed the study showed no difference in efficacy between the two drugs. Seven percent of the olanzapine-treated patients responded according to a priori criteria; no chlorpromazine-treated patients responded. The olanzapine-treated patients had fewer motor and cardiovascular side effects than the chlorpromazine-treated patients. Extrapyramidal symptoms and akathisia were similar in the two groups, although no antiparkinsonian drugs were used in the olanzapine group.
                Olanzapine and chlorpromazine showed similar efficacy, and the total amount of improvement with either drug was modest. Olanzapine-treated patients had fewer side effects than chlorpromazine-treated patients. A prospective double blind study was conducted to evaluate the role of E.C.T. in schizophrenia. Before the start of the trial patients were kept on chlorpromazine in adequate dosage for 30 days. Those who showed fifty percent or more improvement during this period were excluded. All patients were given eight modified or simulated E.C.T.s. The patients were followed up for one month. E.C.T. did not show any added advantage over chlorpromazine either initially or during short term follow-up. 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. In a double blind chlorpromazine-controlled trial, high dosage haloperidol (100 mg daily) given for three months, appreciably improved the mental state of male chronic 'drug resistant' schizophrenic inpatients in the rehabilitation/long-stay unit of one psychiatric hospital. The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug. Serious extrapyramidal side effects were not seen at high doses. However, the majority of patients on haloperidol showed a deterioration in ward behaviour, possibly related to drowsiness, and developed raised serum alkaline phosphatase levels. These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced.
The average dose of chlorpromazine given to people with schizophrenia has declined across time, but this has come about by long - and sometimes hard - experience rather than from direction from high-grade trial-based evidence. This progression towards gentler levels of dosing has taken six decades. We hope that, for modern compounds, data from relevant high-grade evaluative studies will be much more swiftly available to guide informed practice.