You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.



Title 1:
Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.
Abstract 1:
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).


Title 2:
A double-blind comparison of flupenthixol decanoate and fluphenazine decanoate in the treatment of chronic schizophrenia.
Abstract 2:
Sixty-four chronic stabilised schizophrenics were studied for 18 months in order to assess the possible difference in therapeutic effects and side effects between flupenthixol decanoate and fluphenazine decanoate. Although certain differences in the BPRS sub-scores in favour of flupenthixol were present at various stages in the study, there was no significant difference between the two drugs in the overall antipsychotic scores at the end of the assessment period; however, more patients on fluphenating required additional therpay for depression or anxiety during the trial period.


Title 3:
Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia.
Abstract 3:
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.


Title 4:
Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.
Abstract 4:
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.


Title 5:
A comparative trial of depot pipothiazine.
Abstract 5:
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.


Title 6:
The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.
Abstract 6:
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.


Title 7:
The effects of a 50% reduction of cis(z)-flupenthixol decanoate in chronic schizophrenic patients maintained on a high dose regime.
Abstract 7:
Eighteen chronic schizophrenic patients who had shown improvement from increased maintenance dosages of cis(z)-flupenthixol decanoate were entered into a double-blind study in which half of the patients were randomly allocated to be maintained on 50% of their pre-trial dosage. During the 44 week study the reduced dosage group showed increased morbidity and one-third of these patients had a schizophrenic relapse. The greatest deterioration occurred in patients reduced from above to below 200 mg cis(z)-flupenthixol decanoate biweekly. A review of all the patients entered into the study showed a relationship between deterioration of schizophrenic and depressive features and cis(z)-flupenthixol plasma levels which reflected the administered dosage. Prolactin levels in general did not reflect control of schizophrenic symptoms. Side-effects were few, and there was no emergence of tardive dyskinesia. A multicentre trial is needed for further evaluation.


Title 8:
High dose flupenthixol decanoate in chronic schizophrenia.
Abstract 8:
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.


Title 9:
A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency.
Abstract 9:
A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out during 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group. After withdrawal for 6 months, plasma levels for fluphenazine were detectable. Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal. The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics. Furthermore, it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment. The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients.


Title 10:
Peroral and parenteral administration of long-acting neuroleptics: a double-blind study of penfluridol compared to flupenthixol decanoate in the treatment of schizophrenia.
Abstract 10:
Fifty-six out of 60 schizophrenic patients completed a double-blind study of two long-acting neuroleptics, penfluridol (peroral) and flupenthixol decanoate (parenteral). Half of the patients were on maintenance therapy of flupenthixol prior to the study, the other half on penfluridol. The actual double-blind study (12 weeks) was commenced after a preliminary period of 4 weeks, the patients in the two main groups being randomly divided into two further groups, one continuing the medication unchanged, the other changing to the alternative drug. It was found possible to make a sudden switch from penfluridol to flupenthixol decanoate and vice versa without any significant change in the condition of the patient. The same dosage (in 70% of the patients from 40 to 80 mg) of penfluridol was used per week as was employed for flupenthixol decanoate per fortnight. Changes in the intensity of the symptoms (total Brief Psychiatric Rating Scale (BPRS) score) were moe pronounced in the preliminary period (during unchanged treatment) than on changed medication in the blind period. Both drugs induced approximately the same degree of akathisia, Parkinsonism and autonomic side effects. The practical consequences of equipotent therapeutical effect of a peroral and parenteral long-acting neuroleptic are briefly discussed.


Title 11:
Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.
Abstract 11:
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.


Title 12:
Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.
Abstract 12:
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.
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.