Comprehesiven clinical studies with thiothixene. Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study. Double blind study of clopenthixol and chlorpromazine in acute hospitalized schizophrenics. A controlled comparison of clopenthixol and perphenazine in a chronic schizophrenic population. Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study. Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Chemically unrelated antipsychotics as therapeutic alternatives. Clopenthixol: a controlled trial in chronic hospitalized schizophrenic patients. An example of European multicenter trials: multispectral analysis of clozapine. Serum levels of the isomers of clopenthixol in patients given cis(Z)-clopenthixol or cis(Z)/trans(E)-clopenthixol. QEEG alpha 1 changes after a single dose of high-potency neuroleptics as a predictor of short-term response to treatment in schizophrenic patients. Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial. Cis(Z)-clopenthixol and clopenthixol (Sordinol) in chronic psychotic patients. A double-blind clinical investigation. Cis(Z)-clopenthixol and clopenthixol in the treatment of acute psychoses and exacerbations of chronic psychoses. A double-blind clinical investigation. A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients. Cis(Z)-clopenthixol and haloperidol in chronic schizophrenic patients--a double-blind clinical multicentre investigation. The place of thiothixene among the thioxanthenes.
nan Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups. nan nan A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol. nan nan nan The serum levels of the two geometric isomers of clopenthixol and N-dealkylated clopenthixol were estimated in 9 patients, who received cis(Z)-clopenthixol (Cisordinol, Clopixol tabl.) in one period and the double dose of cis(Z)/trans(E)-clopenthixol (Sordinol, Ciatyl) in another period. Nearly equal concentrations of the neuroleptically active isomer, cis(Z)-clopenthixol, were found in the two periods. This finding is in agreement with the clinical experience, but in disagreement with the administered amounts of cis(Z)-clopenthixol, which were larger when the cis(Z)-isomer was given alone. Highly significant correlations were found between dose and mean serum level of cis(Z)-clopenthixol and between dose and area under the serum concentration curves for 8 of the patients, the ninth patient, who had received additional medication showed deviating results. No indication of transformation of cis(Z)-clopenthixol into trans(E)-clopenthixol or vice versa was found. Trans(E)-clopenthixol was found in the serum samples even after administration for one week with the cis(Z)-clopenthixol tablets indicating a relatively long half-life of the trans(E)-isomer. The cis(Z)-isomer of N-dealkyl clopenthixol was found in about the same concentration as cis(Z)-clopenthixol in both periods, while trans(E)-N-dealkyl clopenthixol occurred in about 4 times higher concentrations in patients who had either been given cis(Z)/trans(E)-clopenthixol before they went into the study or had received it in the first period of this study. Baseline quantitative electroencephalographic (QEEG) characteristics and their changes after a single test dose of either haloperidol or clopenthixol were investigated in a group of 29 schizophrenics as possible predictors of short-term response to those drugs. On baseline QEEG assessment, responders (R) to subsequent treatment showed fewer slow and more fast activities than nonresponders (NR). A large overlap between R and NR with respect to these measures was observed, however, revealing their practical inadequacy to predict short-term response in individual patients. On the contrary, changes in alpha 1, observed 6 hr after the administration of a single test dose of either haloperidol or clopenthixol, discriminated to a very large extent between R and NR, correctly identifying 17 out of 18 R and 8 out of 10 NR. The QEEG test dose procedure might be used in the selection of the most appropriate antipsychotic drug for individual schizophrenic patients. A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n = 48) or zuclopenthixol (n = 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication. The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 2-month double-blind trial were included 57 psychotic patients, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning, as well as any individual side effects were done at months 0, 1, and 2. The antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Apart from the finding that the unspecific sedative effect appeared to be less marked with cis(Z)-clopenthixol, the type, degree, and frequency of side effects were the same in the two groups of patients. More than half of the patients experienced no side effects. The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 4-week double-blind trial were included 20 patients with acute psychoses and exacerbations of chronic psychoses, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning were done at weeks 0, 2, and 4, at which occasions also the BPRS was filled in. All patients improved, most of them so much that their final BPRS-score was less than half their initial score. In conclusion, the antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Side effects were few, similar, and equally frequent in the two groups, extrapyramidal side effects and drowsiness being the most common. The therapeutic effect of the neuroleptic cis(Z)-clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double-blind 8-week trial. Forty-nine of the 54 patients in the trial received clopenthixol in the pre-trial period. Ratings with CGI and a single side effects form were done at weeks 0, 2, 4, 6, and 8. The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)-clopenthixol with patient's functioning than by clopenthixol. The ratio of therapeutically equipotent cis(Z)-clopenthixol/clopenthixol doses was found to be 1:2. It is suggested that long-term treatment with clopenthixol advantageously may be replaced by cis(Z)-clopenthixol. Sixty-three chronic schizophrenic in-patients were included in the double-blind, double-dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)-clopenthixol and haloperidol. Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS, NOSIE-30, CGI and single side effects done at weeks 0, 2, 4, 8, and 12. The average end-of-trial doses were 40 mg cis(Z)-clopenthixol and 10 mg haloperidol. Statistically significant improvements of total BPRS-score and Thinking disturbance were registered with both drugs from week 2 onwards. At week 12 when 36 patients were receiving test treatment total BPRS-score was reduced by 31% in the cis(Z)-clopenthixol group and by 17% in the haloperidol group. At week 4 Thinking disturbance was reduced by 32% in the cis(Z)-clopenthixol group and by 16% in the haloperidol group--these findings constituted the only significant difference between test drugs. Compared to the BPRS-results less improvements and no differences between test drugs were registered with NOSIE-30 and CGI. Any trends towards different frequency and severity of side effects were in the favour of cis(Z)-clopenthixol. nan
There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.
Note: the 8 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.