Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate. High dose flupenthixol decanoate in chronic schizophrenia. The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry. Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia. Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison. A depot neuroleptic withdrawal study. A controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients. Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia. Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology. A comparative trial of depot pipothiazine.
Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug. In a double-blind trial, female 'drug-resistant' chronic schizophrenic in-patients were given high dose or standard dose flupenthixol decanoate for 13 weeks. Plasma flupenthixol levels showed a five-fold interindividual variation, but were consistently higher with the high dose. Analysis of final scores showed no statistically significant differences between groups with regards to mental state, ward behaviour and extrapyramidal side-effects. When compared with pre-trial scores, the extrapyramidal side-effects worsened significantly in the high dose patients and social withdrawal decreased in the standard dose patients. The mental state of a sub-group of patients, possibly drug resistant for pharmacokinetic reasons, improved significantly on the high dose over the 13 weeks. Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed. The clinical and social effects of flupenthixol decanoate and fluphenazine decanoate were compared in the maintenance treatment of a population of chronic schizophrenic out-patients over a period of 9 months. The results failed to show significant difference between the treatments, and in particular, reports suggesting specific advantages for flupenthixol decanoate in alleviating the negative symptoms of apathy, anergia and depression in chronic schizophrenics were not confirmed. It seems that chronic schizophrenic patients who are well established on one depot preparation are unlikely to be benefited by being changed to the alternative. Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals. A double-blind withdrawal trial in 41 chronic schizophrenic outpatients on neuroleptics was carried out during 6 months. Long-acting neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were used in comparison with placebo to determine the value in maintenance therapy. Most patients had a rather low maintenance dose, about 12.5-25 mg fluphenazine decanoate or 20-40 mg flupenthixol decanoate every third week. Relapse was often characterized by a return of the dame symptoms as the patient had during his first schizophrenic attack. Drugs were significantly more effective than placebo in preventing relapse and readmission to hospital. 62% relapsed in the placebo groups as compared with 27% in the drug group. All patients on active substance and without relapse during the controlled study had their treatment discontinued for 24 months in an open follow-up investigation. This resulted in relapse of all patients but one, i.e. a final relapse frequency of 97%. A significant weight decrease was observed in the placebo group. The risk of withdrawal is discussed. A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested. Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate). Thirty-nine chronic schizophrenic patients were selected for a 12-month double-blind evaluation of the effectiveness of pipothiazine palmitate (PPT) and flupenthixol decanoate (FPX) in the maintenance management of their illness. Allocation was at random and, in order to allow constant injection intervals, the patients typically received every 2 weeks either 40 mg of flupenthixol decanoate or alternating injections of 100 mg of pipothiazine palmitate and placebo. At monthly intervals the patients were assessed using both a battery of rating scales (which included the Brief Psychiatric Rating Scale (BPRS), the Extrapyramidal Symptoms Rating Scale (EPS] and a general side-effects evaluation. At 3-monthly intervals they were also rated on the Comprehensive Psychiatric Rating Scale (CPRS) and the Zung Depression Scale. Haematological and biochemical tests were performed every 3 months. Both drugs provided good control of psychotic symptoms and side-effects were not troublesome. No substantial difference was detected on the CPRS and the Zung scales. There was a trend in favour of PPT on the BPRS survey, detectable at 6 months and reaching statistical significance by 12 months. We conclude that the PPT regime is at least as effective as the FPX treatment and probably more so. It is possible that even longer periods of control could be obtained with PPT.
From the data reported in clinical trials, it would be understandable if those suffering from schizophrenia, who are willing to take flupenthixol decanoate, would request the standard dose rather than the high dose. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. The choice of which depot to use must therefore be based on clinical judgement and the preferences of people with schizophrenia and their carers. Managers and policy makers should expect better data than the research community has provided thus far.
This review highlighted the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate, in particular when compared to oral antipsychotics. Future studies should also consider hospital and service outcomes, satisfaction with care and record economic data.