clopenthixol-acetate-ester and Schizophrenia

Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). Although it has been in common use for many years no previous systematic review of its efficacy compared to placebo in schizophrenia has been undertaken.. To evaluate the effectiveness of all formulations of zuclopenthixol when compared with a placebo in schizophrenia.. On 6 November 2013 and 20 October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. We also checked the references of all included studies and contacted authors of included studies for relevant studies and data.. We included all randomised controlled trials comparing zuclopenthixol of any form with placebo for treatment of schizophrenia or schizophrenia-like psychoses.. We extracted and cross-checked data independently. We identified only a small number of studies so we cross checked all studies. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. Where possible we converted continuous outcomes into dichotomous outcomes. When this was not possible we used mean differences (MD) for continuous variables. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.. Only two studies, with a total of 65 participants, were eligible for inclusion in the review. Overall the quality of the two studies was low, with small study populations and significant sources of bias, so we were not able to use all the data in our comparisons. . The studies were old from 1968 and 1972, and would be unlikely to pass modern peer review standard. We were only able to find short-term data and only trials randomising zuclopenthixol dihydrochloride. We also hoped to identify data for zuclopenthixol acetate versus placebo and zuclopenthixol decanoate versus placebo comparisons. We were unable to identify any studies that included data on these two fairly widely used drugs.For our primary outcome of interest, clinically significant improvement, we found one study that provided useable data. Global state measured by clinical global impression scale (CGI) improvement showed different ratings when assessed by a psychiatrist or a nurse.The psychiatrist scores failed to achieve statistical significance, however when assessed by nursing staff, the difference favouring zuclopenthixol did reach statistical significance (1 RCT n = 29, RR 2.57 95% CI 1.06 to 6.20, very low quality data). There was also evidence of increased sedation with those treated with zuclopenthixol when compared with placebo (1 RCT n = 29, RR 4.67 95% CI 1.23 to 17.68, very low quality data). 'Leaving the study early' data were equivocal. No useable data were available for outcomes such as relapse, mental state, death, quality of life, service use or economic costs.. For people with schizophrenia this review shows that zuclopenthixol dihydrochloride may help with the symptoms of schizophrenia. The review provides some trial evidence that, if taking zuclopenthixol dihydrochloride, people may experience some adverse effects and sedation compared with placebo. However this evidence is of very low quality and with some significant sources of bias. There are no data for zuclopenthixol decanoate or zuclopenthixol acetate.For clinicians, the available trial data on the absolute effectiveness of zuclopenthixol dihydrochloride do support its use but the limited nature of the data and significant sources of bias make conclusions hard to draw. Zuclopenthixol in all three forms is a commonly used antipsychotic and it is disappointing that there are so few data regarding its use.

Topics: Antipsychotic Agents; Clopenthixol; Humans; Randomized Controlled Trials as Topic; Schizophrenia

The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Double-Blind Method; Female; Haloperidol; Humans; Male; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Arousal; Clopenthixol; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Neurologic Examination; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

In this study we report the results of two experiments on visual attention conducted with patients with early-onset schizophrenia. These experiments investigated the effect of irrelevant spatial-scale information upon the processing of relevant spatial-scale information, and the ability to shift the spatial scale of attention, across consecutive trials, between different levels of the hierarchical stimulus. Twelve patients with early-onset schizophrenia and matched controls performed local-global tasks under: (1) directed attention conditions with a consistency manipulation and (2) divided-attention conditions. In the directed-attention paradigm, the early-onset patients exhibited the normal patterns of global advantage and interference, and were not unduly affected by the consistency manipulation. Under divided-attention conditions, however, the early-onset patients exhibited a local-processing deficit. The source of this local processing deficit lay in the prolonged reaction time to local targets, when these had been preceded by a global target, but not when preceded by a local target. These findings suggest an impaired ability to shift the spatial scale of attention from a global to a local spatial scale in early-onset schizophrenia.

Topics: Adolescent; Affect; Antipsychotic Agents; Attention; Benzodiazepines; Clopenthixol; Diazepam; Female; Flupenthixol; Frontal Lobe; Humans; Male; Olanzapine; Parietal Lobe; Perceptual Disorders; Pirenzepine; Reaction Time; Risperidone; Schizophrenia; Space Perception; Time Factors

We report a case of neuroleptic malignant syndrome where the catatonia clearly followed the administration of neuroleptics and where the neurovegetative disturbance was remarkably severe, including episodes of tracheal spasm, apnoea and episodes of bradycardia, and sinus arrest requiring insertion of a temporary external pacing wire. To our knowledge, such severe disturbance has not previously been reported.

Topics: Adult; Antipsychotic Agents; Cardiac Pacing, Artificial; Catatonia; Chlorpromazine; Clopenthixol; Drug Therapy, Combination; Electrocardiography; Female; Haloperidol; Heart Arrest; Humans; Neuroleptic Malignant Syndrome; Neurologic Examination; Schizophrenia

Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer trans(E)-clopenthixol were determined by high-performance liquid chromatography after intramuscular injection. All patients improved, with the BPRS being significantly reduced (p < 0.001) at 72 h after injection. Adverse effects were generally few. The mean +/- SEM serum zuclopenthixol concentrations at 24, 48, and 72 h were 19.9 +/- 2.8, 31.5 +/- 4.5, and 17.8 +/- 2.9 micrograms/L, respectively. trans(E)-Clopenthixol concentrations ranged from negligible to 39.5 micrograms/L. This study confirms that a single intramuscular injection of 50 mg is adequate for managing severely disturbed psychotic patients for the first 3 days. The serum zuclopenthixol concentrations attained in the Asian patients were higher than those reported in Caucasian psychiatric patients. In some patients, a considerable amount of zuclopenthixol had been transformed to trans(E)-clopenthixol.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; China; Clopenthixol; Female; Humans; India; Injections, Intramuscular; Malaysia; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Singapore

1. The zuclopenthixol concentrations in serum has been investigated in man and dog after injection of three different zuclopenthixol preparations. These were zuclopenthixol dihydrochloride in aqueous solution, zuclopenthixol acetate in oil and zuclopenthixol decanoate in oil. 2. The pharmacokinetic profiles of the three injectable zuclopenthixol preparations are very different. Maximum serum levels are obtained after about 1 hour for zuclopenthixol dihydrochloride, after 36 hours for zuclopenthixol acetate and after one week for zuclopenthixol decanoate. 3. The different pharmacokinetics of the three injectable zuclopenthixol preparations are reflected in their clinical properties.

Topics: Adult; Aged; Animals; Antipsychotic Agents; Clopenthixol; Dogs; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Psychotic Disorders; Reference Values; Schizophrenia; Thioxanthenes