clopenthixol-decanoate 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

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Flupenthixol; Fluphenazine; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Movement Disorders; Psychiatric Status Rating Scales; Risperidone; Schizophrenia

Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clopenthixol; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sex Factors

Whole blood and plasma concentrations of active neuroleptic drugs were measured in eight schizophrenic outpatients who had received cis(Z)-clopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil by intramuscular injection. Whole blood and plasma concentrations were very similar, though there was a slight tendency for blood concentrations to be higher than plasma concentrations. Maximum concentrations appeared at 1 week after administration of cis(Z)-clopenthixol decanoate, whereas the highest concentrations after fluphenazine decanoate were seen at the end of the 3-week dosage interval. Some between-individual variation and a limited within-individual variation was seen.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Fluphenazine; Humans; Injections, Intramuscular; Kinetics; Male; Middle Aged; Radioimmunoassay; Schizophrenia; Thioxanthenes

Forty-five patients were entered into a 24-week double-blind trial of clopenthixol decanoate and fluphenazine decanoate. The 24-week double-blind period was preceded by a 12-week open period. Of the 45 patients entered, 6 failed to attend the second interview and 1 left the country before the final assessment. Doses administered were in the range 100 mg 4-weekly to 400 mg 2-weekly for clopenthixol decanoate and 12.5 mg 4-weekly to 37.5 mg 3-weekly for fluphenazine decanoate. Both depot neuroleptics appeared to have an equivalent duration of action, with 200 mg clopenthixol decanoate approximately equivalent to 25 mg fluphenazine decanoate. Patients' mental state was assessed on the Brief Psychiatric Rating Scale, Clinical Global Impression, Krawiecka, Goldberg and Vaughan Rating Scale, and unwanted effects were recorded on a checklist. No differences were detected between the two drugs with regard to therapeutic activity or side-effects. It is concluded that clopenthixol decanoate is as effective and as well-tolerated a depot neuroleptic as fluphenazine decanoate.

Topics: Antipsychotic Agents; Chronic Disease; Clinical Trials as Topic; Clopenthixol; Delayed-Action Preparations; Double-Blind Method; Fluphenazine; Humans; Psychiatric Status Rating Scales; Schizophrenia; Thioxanthenes

Schizophrenia is a serious long-term mental disorder which usually presents in adolescence or early adulthood. However, poor adherence to oral antipsychotics can lead to relapse and rehospitalisation. We report an adolescent male with schizophrenia who was referred to the South London & Maudsley National Health Service Foundation Trust, London, UK, in 2015 due to worsening psychotic symptoms. Following poor compliance with oral medications, a four-week regimen of paliperidone palmitate long-acting injections was initiated, with an initial positive response. However, 10 days after the second dose, the patient developed severe acute-onset delirium with fluctuating levels of consciousness. Paliperidone palmitate was discontinued and the patient instead underwent a course of zuclopenthixol decanoate long-acting injections with a favourable outcome.

Topics: Activities of Daily Living; Adolescent; Antipsychotic Agents; Clopenthixol; Delirium; Drug Substitution; Humans; Male; Medication Adherence; Paliperidone Palmitate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Drug Therapy, Combination; Female; Humans; Risperidone; Schizophrenia; Treatment Outcome

Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature.. A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (to approximately 3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with haloperidol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success.. A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Schizophrenia

Poor response to antipsychotics is still an important problem in the treatment of many schizophrenia patients. N-acetylcysteine (NAC) is a compound that exerts anti-oxidant and scavenging actions against reactive oxygen species. This paper reports a case of poorly responsive schizophrenia patient who improved considerably with add-on NAC 600 mg/day. The NAC might work through activating cysteine-glutamate antiporters or reducing in nitric oxide (NO) metabolites, free radicals and cytokines or through both of these mechanisms.

Topics: Acetylcysteine; Adult; Antipsychotic Agents; Benzodiazepines; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Free Radical Scavengers; Humans; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Neuroleptic malignant syndrome (NMS) is a rare clinical condition and potentially life-threatening complication of antipsychotic medications. We report a patient with an atypical presentation of NMS. A 60-year-old man with schizophrenia was admitted to our hospital with disturbed consciousness, fever and marked extrapyramidal rigidity both in the upper and lower extremities. He had been given i.m. zuclopenthixol 200 mg/month but had not taken the last dose. Laboratory investigations showed that creatinine phosphokinase 428 IU/l (normal up to 130), lactate dehydrogenase 772 IU/l (normal up to 450), blood glucose 256 mg/dl (65-110). Urine analyses revealed ketonuria. White blood cell (WBC) count was 6100 cells/mm(3). Therefore, the patient was diagnosed as having NMS and antipsychotic medications were stopped. Adequate hydration was provided and bromocryptine 5 mg was started three times a day. Despite treatment, the patient died due to acute myocardial infarction after 3 days of hospitalization.

Topics: Antipsychotic Agents; Clopenthixol; Creatine Kinase; Delayed-Action Preparations; Diagnosis, Differential; Fatal Outcome; Fever of Unknown Origin; Humans; Hyperglycemia; Injections, Intramuscular; Male; Middle Aged; Myocardial Infarction; Neuroleptic Malignant Syndrome; Schizophrenia; Shock, Cardiogenic

To report a case of recurrent heat-related illnesses associated with the use of benzhexol, chlorpromazine, and zuclopenthixol decanoate.. During the summer of 2004, a 48-year-old man with a history of diabetes mellitus and schizophrenia was twice admitted to the hospital because of heat-related illnesses. On both occasions, he had been working under the sun in an open car park. His medications included benzhexol 2 mg twice daily, chlorpromazine 650 mg at bedtime, and zuclopenthixol decanoate intramuscular injection 600 mg every 4 weeks. In the first admission, the clinical diagnosis was heat stroke. He was discharged home on day 14, with precautionary advice against heat stroke. In the second admission, the clinical diagnosis was heat exhaustion. He was discharged home on day 4 and reminded of the precautions against heat stroke. An objective causality assessment revealed that the adverse event was possibly drug related in the first admission and probably drug related in the second admission.. Several drugs can impair thermoregulation during exercise or under conditions of environmental heat stress. Anticholinergic drugs or drugs with anticholinergic effects can inhibit sweating and reduce heat elimination. Neuroleptics (antipsychotics), such as phenothiazines, have combined anticholinergic and central thermoregulatory effects. The set point of the temperature regulation center can be elevated by the antidopaminergic effect of antipsychotics, such as phenothiazines and thioxanthenes.. Certain drugs may induce or worsen heat-related illnesses. During a heat wave, special attention should be given to those most at risk, and the importance of preventive measures should be emphasized.

Topics: Antipsychotic Agents; Body Temperature Regulation; Chlorpromazine; Clopenthixol; Diabetes Complications; Heat Exhaustion; Heat Stroke; Humans; Male; Middle Aged; Muscarinic Antagonists; Recurrence; Schizophrenia; Trihexyphenidyl

Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established.. To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate.. Fifty-two clinically stable schizophrenic outpatients on monotherapy with zuclopenthixol-decanoate (100-400 mg/4 weeks) were genotyped for the CYP2D6 variants CYP2D6*3 and CYP2D6*4. Steady-state plasma levels of zuclopenthixol were analysed using high-performance liquid chromatography. Assessments of EPS, TD and psychopathology were performed twice with an 8-week interval using the extrapyramidal symptoms rating scale, the abnormal involuntary movement scale and the brief psychiatric rating scale.. Thirty-five patients were homozygous extensive metabolisers (EMs), 13 were heterozygous EMs and 4 were poor metabolisers (PMs). While there were no significant genotype-related differences in the doses of zuclopenthixol decanoate, PMs as well as heterozygous EMs had significantly higher steady-state plasma levels of zuclopenthixol than homozygous EMs (median 9.5 nmol/l; 8.2 nmol/l and 5.9 nmol/l, respectively, P<0.05). The median dose-corrected plasma concentrations were 0.029, 0.038 and 0.048 nmol.l(-1).mg(-1) in homozygous EMs, heterozygous EMs and PMs, respectively, with statistically significant differences between homozygous EMs and heterozygous EMs ( P=0.014) and homozygous EMs and PMs ( P=0.03). Patients with neurological side effects were significantly older than patients without ( P=0.02 in case of parkinsonism and P=0.04 in case of TD). Mutant CYP2D6*3 and *4 alleles tended to occur more frequently in patients with neurological side effects. An odds ratio (OR) of 2.3 (95% confidence interval 0.7-6.9) for development of parkinsonism and an OR of 1.7 (95% confidence interval 0.5-4.9) for TD was calculated in an individual with at least one mutated allele. However, the ORs were not statistically significant.. The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with zuclopenthixol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclopenthixol. The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies. Age was a significant risk factor for neurological side effects.

Topics: Adult; Aged; Analysis of Variance; Chi-Square Distribution; Clopenthixol; Confidence Intervals; Cytochrome P-450 CYP2D6; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Odds Ratio; Parkinsonian Disorders; Polymorphism, Genetic; Regression Analysis; Schizophrenia

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

Seventeen outpatients were treated with depot neuroleptics, zuclopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil, with dosage intervals of 3 weeks. During the 4th, 6th, and 8th dosage interval blood samples were drawn in oxalated tubes. Plasma concentrations of the active neuroleptic drugs, zuclopenthixol and fluphenazine, were determined by high performance liquid chromatography. The concentrations indicated some interindividual as well as intraindividual variations. For zuclopenthixol the maximum concentration was most often seen at day 7 after injection, whereas the kinetics of the fluphenazine concentrations was more variable. There was an indication of more fluctuation in the 4th dosage interval than in the 8th dosage interval, possibly due to the fact that steady state has not yet been achieved at the 4th dosage interval.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Female; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes; Tranquilizing Agents

Twenty-six patients diagnosed as chronic schizophrenics were given injections of zuclopenthixol decanoate (cis(Z)-clopenthixol decanoate) 200 mg every 3 weeks for at least 6 months. Before treatment and on each day of injection the patients' mental state was assessed by Brief Psychiatric Rating Scale (BPRS), 18 items. A registration of side effects and basal laboratory data was also performed. Blood samples were drawn on each day of injection before injection and 3-7 days after injection (time of maximum concentration). Neuroleptic activity, which was considered equivalent to the concentration of zuclopenthixol, was determined in serum by radio-receptor assay (RRA). Based on amelioration scores greater than or equal to 50% on the BPRS, 15 patients were characterized as responders and 11 as non-responders. The responder group showed a statistically significant reduction in BPRS score, whereas this was not the case for the non-responders. Apart from a few patients, the serum concentrations showed a low intra-individual variation, but a relatively high inter-individual variation. The responder group had a significantly higher mean pre-injection concentration than the non-responder group, whereas no significant difference was found in day 3-7 concentrations. The fluctuation of the serum concentration expressed as the ratio between maximum (days 3-7) and minimum (pre-inj.) was found to be significantly lower for responders than for non-responders. Thus although the present study did not demonstrate a clear relationship between serum level and clinical effect, it indicates that the best antipsychotic effect is obtained with a serum concentration which fluctuates only slightly (the ratio max/min concentration not exceeding 2.1).

Topics: Adult; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Clopenthixol; Female; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.

Topics: Adult; Aged; Clopenthixol; Female; Flupenthixol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Recurrence; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Thioxanthenes

Nineteen chronic schizophrenics were included in an open trial to evaluate the depot neuroleptic, zuclopenthixol decanoate. The treatment period was 24 weeks and clinical evaluations were carried out every 4 weeks including the CGI, the BPRS (completed at Weeks 0, 4, 8, 16, and 24), the Hamilton Depression Scale (completed at Weeks 0, 12, and 24), and a side-effects check list. Patients received 200 mg zuclopenthixol decanoate intramuscularly at intervals dependent on the severity of the illness. Statistically significant reductions were found for most of the symptoms on the BPRS. The reduction was already seen after 4 weeks of treatment. A clear improvement was also recorded on the Hamilton Depression Scale. The frequency of side-effects was low and decreased during the treatment period. The side-effects recorded were mild and, according to the CGI, they did not interfere with the patients' functioning except in 1 case (Week 24). It is concluded that zuclopenthixol decanoate is an effective and well-tolerated drug in the maintenance treatment of chronic schizophrenia.

Topics: Adult; Aged; Chronic Disease; Clopenthixol; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Thioxanthenes

Topics: Adolescent; Adult; Clopenthixol; Female; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Attempting to improve long-term neuroleptic treatment of schizophrenic patients several injectable depot neuroleptics have been developed. Moreover pharmacokinetic data increasingly have been clinically applied. On this background the purpose of the present paper has been to make an updated review of the clinical and pharmacokinetic knowledge of depot neuroleptic treatment. First, general aspects of antipsychotics have been summarized, and an outline of methodological questions relevant to clinical-pharmacological trials are given. Subsequently general aspects including pros & cons of depot administration are examined. Finally the available data of the various depot preparations have been scrutinized. It is concluded that our present pharmacokinetic knowledge of the particular preparations is incomplete. Thus more information of clinical relevant aspects are needed, e.g., the existence of a therapeutic range, maximum/minimum concentration ratio, and the significance of active metabolites. Comparing the various depot neuroleptics, no significant differences are seen regarding the clinical effects. However, the decanoate esters seem clinical superior to the corresponding enanthate esters explained by the more flat concentration curve of the decanoates. Apart from that, a comparison of the pharmacokinetic data is difficult because of the heterogenecy of the available data. Haloperidol, clopenthixol and perphenazine decanoates are among the best examined preparations in pharmacokinetic respects. A controlled double-blind comparative study of these preparations would be of interest.

Topics: Administration, Oral; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Haloperidol; Humans; Kinetics; Long-Term Care; Patient Compliance; Perphenazine; Schizophrenia; Schizophrenic Psychology; Thiazines

An open, multi-centre study was carried out in 69 patients with an acute psychotic episode to assess the efficacy and side-effects of treatment with oral zuclopenthixol dihydrochloride. Patients were treated until the acute episode was considered terminated by the clinician and, although dosage could be adjusted to allow optimum clinical response, the majority received 25 mg zuclopenthixol dihydrochloride 3-times daily throughout the trial period. Assessments were made before and during treatment using the BPRS and CGI rating scales and a check-list of side-effects. The results showed that 55 (80%) patients had a successful response to treatment. Almost half (33) of the patients responded fully to the drug within 3 weeks and by the end of 5-weeks' treatment this had increased to over 70% (49). A further 6 patients responded after 6 to 9 weeks of treatment. The drug was generally well tolerated and the majority of patients had either no side-effects or side-effects which did not overtly affect performance.

Topics: Adolescent; Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Sex Factors; Thioxanthenes; Time Factors

Topics: Adult; Antipsychotic Agents; Clopenthixol; Female; Humans; Male; Schizophrenia; Thioxanthenes

A study was carried out in 68 chronic schizophrenic out-patients to assess the therapeutic effectiveness and tolerance of long-term maintenance treatment with a depot preparation of clopenthixol decanoate. Patients received 200 mg to 600 mg doses by intramuscular injection every 2 to 3 weeks for a mean treatment period of 20.3 months. Clinical symptomatology was assessed at regular intervals using the Brief Psychiatric Rating Scale (BPRS) and any adverse effects were recorded against a standard check-list. The results showed that there was a significant reduction in total and factor composition BPRS scores after treatment in all patients, the improvement becoming generally evident by the sixth month of treatment. Few autonomic and neurological side-effects were reported.

Topics: Adult; Aged; Antipsychotic Agents; Chronic Disease; Clopenthixol; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Thioxanthenes; Time Factors

Twenty-three chronic schizophrenic patients were followed-up over periods up to 5 years (1978-1983) while receiving treatment with depot injections of clopenthixol decanoate in doses ranging from 100 to 600 mg every 2 to 4 weeks. The highest single dose given was 1600 mg. Improvement in psychotic symptoms occurred progressively over the 5 years, with reduction in mean overall symptom score for schizophrenia from 7.43 to 0.88. Mean side-effects scores decreased over the same period from 2.0 to 0.5. After 5 years, 10 patients were still maintained on clopenthixol decanoate. Although during the first 2 months there was little improvement in 'negative' or 'loss' symptoms, improvement was similar in 'positive' and 'negative' symptoms after 5 years. Clopenthixol decanoate appeared to have a better calming effect than that encountered with flupenthixol decanoate. At higher doses, it caused drowsiness and subdued hostility and aggression.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Chronic Disease; Clopenthixol; Female; Follow-Up Studies; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Nineteen chronic schizophrenic in-patients were entered into a 12-week open study of intramuscular clopenthixol decanoate. Fourteen patients completed the full 12-week treatment period; 3 were withdrawn due to inadequate clinical response or untoward adverse effects, and 2 were discharged and lost to follow-up. Doses administered were in the range 200 to 400 mg, weekly or fortnightly. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS). Nurses' Observation Scale for In-patient Evaluation (NOSIE-30) and the Clinical Global Impression (CGI). Unwanted effects were recorded on a checklist. Statistically significant improvements in the overall mean scores were noted on the BPRS at every assessment and on the NOSIE-30 at every assessment except in Week 4. Unwanted effects were generally mild and they decreased during the study. The results suggest that clopenthixol decanoate is an effective, well-tolerated antipsychotic agent, suitable for the treatment of chronic, long-stay schizophrenic in-patients.

Topics: Adult; Aged; Chronic Disease; Clopenthixol; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Thioxanthenes; Time Factors

cis(Z)-Clopenthixol decanoate is a new depot neuroleptic that belongs to the group of thioxanthenes. It has a duration of effect ranging from 2 to 4 weeks and it is used for long-term therapy of chronic schizophrenic patients. The aim of this review is to represent the chemistry, pharmacology, pharmacokinetics, dosage and efficacy of this drug. The target symptoms that essentially call for the application of cis(Z)-clopenthixol decanoate are hostility, suspiciousness and psychomotor restlessness. However, a distinct therapeutic effect has also been observed in patients with hallucinatory-disintegrative and manic syndromes. Moreover, the depot preparation also called forth an emotional stabilization among alcoholics as well as a mitigation of alcohol withdrawal symptoms.

Topics: Chemical Phenomena; Chemistry; Clopenthixol; Delayed-Action Preparations; Humans; Kinetics; Schizophrenia; Thioxanthenes; Time Factors

Clopenthixol decanoate was given to 20 chronic schizophrenic patients for 11 months in doses ranging from 100 mg initially up to 1000 mg 3-weekly subsequently, according to clinical response and the occurrence of adverse effects. A further 3 patients received the depot injections for periods of 6 to 9 months. Improvement in individual symptoms was rated on a 4-point scale. Unwanted effects were recorded on a checklist and routine biochemical and haematological tests were carried out at the beginning and end of the treatment period. There were highly significant improvements in the mean overall symptom score and in the 5 single symptom scores (hallucinations, delusions, depression, aggressive behaviour and non-aggressive behaviour disturbance). The 2 'negative' symptoms of apathy and social withdrawal showed improvement up to 16 weeks but not at 11 months. The incidence of depression was less at the end of the study than at the time fo entry. Three patients stopped the drug after the sixth month because of extrapyramidal symptoms (2) or drowsiness (1). Three others developed severe extra-pyramidal side-effects. Unwanted effects, though recorded in 70% of patients--drowsiness and extrapyramidal symptoms were the commonest--were for the most part trivial, and were fewer and less severe than they were on entry to the study. There was no evidence of toxicity. It was considered that on the basis of this experience the drug was an effective, safe antipsychotic agent, warranting more extensive clinical trial.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clopenthixol; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Thioxanthenes