Depot fluspirilene for schizophrenia.

BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To review the effects of depot fluspirilene versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (September 2005), inspected references of all identified studies, and contacted relevant pharmaceutical companies. SELECTION CRITERIA: We included all relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics, other depot preparations, or placebo were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data, we calculated relative risk (RR) with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. We summated normal continuous data using the weighted mean difference (WMD). We presented scale data only for those tools that had attained pre-specified levels of quality. MAIN RESULTS: We included twelve randomised studies in this update of which five are additional studies. One trial compared fluspirilene and placebo and did not report important differences in the global improvement (n=60, 1 RCT, RR "no important improvement "0.97 CI 0.9 to 1.1). Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate. We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early. Global state data (CGI) were not significantly different, in the short term when comparing fluspirilene with other depots (n=90, 2 RCTs, RR "no important improvement" 0.80 CI 0.2 to 2.8). No significant difference were apparent between fluspirilene and other depots with respect to the number of people leaving the trial early (n=83, 2 RCTs, RR 0.55 CI 0.1 to 2.3) or relapse rates (n=109, 3 RCTs, RR 0.55 CI 0.1 to 2.3). Extrapyramidal adverse effects were significantly less prevalent in the fluspirilene groups (n=164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5). Other adverse effects were not significantly different. Attrition in the one comparison between fluspirilene in weekly versus biweekly administration (n=34, RR 3.00 CI 0.1 to 68.8) and relapse rates (n=34 RR 3.18 CI 0.1 to 83.8) were not significantly different. There were no significant difference for movement disorders in one short term study. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies. AUTHORS' CONCLUSIONS: Participant numbers in each comparison were small and we found no clear differences between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice.

[Interaction of therapeutic effects and side effects in drug therapy of generalized anxiety disorders with low dosage fluspirilene]. / Interaktion von therapeutischen Wirkungen und Nebenwirkungen in der Pharmakotherapie generalisierter Angststörungen mit niedrigdosiertem Fluspirilen.

The present study was designed to investigate the interaction between therapeutic effects and side-effects in fluspirilene treatment of generalised anxiety disorders (GAD). 205 outpatients received in an open trial 1.5 mg fluspirilene per week for 6 weeks. Confirming previous reports of our study group fluspirilene demonstrated marked efficacy and was generally well tolerated. However, the main finding of our study is that side effects, although rare in fluspirilene treatment, predict an unfavourable clinical outcome. This phenomenon is integrated in a psychological model implying that when GAD patients are aware of side-effects this induces anxiety. Again anxiety gives rise to somatic symptoms, both interacting in a forward loop. In conclusion, our data suggest that in the sense of Heinrich (1988) fluspirilene treatment of GAD should be guided by paying attention to possible side effects.

Correct titration of non-drugs and some other methodological issues.

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

[Severe "late" dystonia after neuroleptic anxiolysis with fluspirilene]. / Schwere "Spät" dystonie nach "Neuroleptanxiolyse" mit Fluspirilen.

The development of severe tardive dystonia after short-term use of low-dose Fluspirilen is described. A 39-year-old woman was treated with Fluspirilen IM by her family doctor for reactive depression. She did received no other neuroleptic agents and no risk factors for the development of tardive dyskinesia (e.g. old age or organic brain damage) were present. For the first time a relation between short-term monotherapy with Fluspirilen and tardive dyskinesia appears highly probable. The use of Fluspirilen for the treatment of psychogenic disturbances should therefore be considered carefully.

[The role of the nurse in the clinical use of IMAP]. / Papel de la enfermera en la clinica del IMAP.

A survey was carried out on patients treated with Fluspirilene (IMAP) at the Mental Health Dispensary from January 1, 1987, to January 1, 1988. An analysis is made on the evolution of the patients given this treatment and extrapyramidal reactions observed, the cases hospitalized in spite of the treatment and the criteria of family members regarding the drug. A statistical discussion is made about the results shown in tables about the study carried out.

Safety of long-term neuroleptanxiolysis with fluspirilene 1.5 mg per week.

In recent years concern has been frequently expressed that a long-term treatment with fluspirilene 1.5 mg/week might induce tardive dyskinesia, yet there are no empirical data from controlled studies available. In 11 private practices 276 patients under long-term treatment with either fluspirilene or benzodiazepines for reasons of anxiety or psychoneurotic or psychosomatic disorders were investigated by an independent and specially trained physician from our hospital with regard to symptoms to tardive dyskinesia, parkinsonism, and akathisia. Of these patients, 155 had received fluspirilene 1.5 mg/week with a mean duration of treatment of 17.5 months (s = 13.3), and 121 had received benzodiazepines with a mean duration of treatment of 45.7 months (s = 44.6). The mean total scores of the AIMS, the Simpson Angus Scale, and an akathisia scale did not differ significantly between the two groups. In the fluspirilene group a positive correlation of age and psychotropic comedication with the total scores of the AIMS and the akathisia scale could be found, but there was no correlation between duration or continuity of treatment with fluspirilene and symptoms of tardive dyskinesia. In each of the two groups 10 patients (6.9% of the fluspirilene group and 8.3% of the benzodiazepine group) showed abnormal involuntary movements, which corresponds to the incidence of spontaneous dyskinesia. The results of this study do not indicate an increase in tardive dyskinesia for patients with a mean duration of treatment with fluspirilene 1.5 mg/week of 18 months.

The dose-effect relationship of 0.5, 1.0 and 1.5 mg fluspirilene on anxious patients.

To investigate the dose-effect relationship, 106 patients received for 6 weeks under double-blind conditions randomly either 0.5 (n = 35), 1.0 (n = 35) or 1.5 mg (n = 36) fluspirilene per per week. Two patients dropped out. The main result of this study was the verification of a clear dose-effect relationship. There is a difference between all three dosage groups after 6 weeks. Improvement with 0.5 mg fluspirilene was far more seldom (17 of 35) than with 1.0 mg (25 of 33) and very much more frequent with 1.5 mg (30 of 36). This was confirmed with the three scales of the Hamilton Anxiety Scale. The clear dose-effect relationship was also shown on the subjective 'Eigenschaftswörterliste' scales of elation, self-confidence, introversion, anxiety, vulnerability and depression. The tolerance of all doses in this study was good and did not differ. Nevertheless, the findings from earlier studies were reproduced, according to which a poorer tolerance is combined with a poorer therapeutic efficacy. It was worked out in the discussion that patients who improved subjectively and according to the physician's assessment after 14 days of treatment also showed a good response after a longer period of treatment.

A controlled clinical trial of fluspirilene, a long-acting injectable neuroleptic, in schizophrenic patients with acute exacerbation.

A 4-week double-blind controlled clinical trial was carried out in which fluspirilene, an injectable diphenylbutylpiperidine neuroleptic given weekly, was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. Similar therapeutic improvement was obtained with both drugs, but men needed a significantly higher mean dose of fluspirilene (23 mg/week) than women (13 mg/week). Fluspirilene induced more parkinsonism than chlorpromazine, but less drowsiness, dizziness, and dry mouth. The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties. The low incidence of autonomic side effects confirms the relative specificity of fluspirilene for dopamine receptors.

[New long-acting treatment of anxiety and its different forms of somatization: low-dose fluspirilene]. / Un nuovo trattamento long-acting dell'ansia e delle differenti forme della sua somatizzazione: fluspirilene low-dose.

After pharmacological considerations on fluspirilene, a diphenylbutylpiperidinic neuroleptic with a tranquillizing action in neurotic syndromes, the Authors refer on 24 patients with a normal social behaviour treated with low dosage. I.M. weekly dosages of 1.5 mg have been used for 6 weeks with semi-quantitative evaluation of 1-5 psychic items, 10 neurovegetative items and 36 miscellaneous. A significant improvement was obtained for nearly all symptoms and did not cause variations in bodyweight, pressure values and pulse frequency or local or systemic intolerance. Positive results reached 77.3% of treated cases, in agreement with those reported by numerous foreign Authors.

[A comparative study of the longacting neuroleptics perphenazin-enanthate and fluspirilene (author's transl)]. / Eine vergleichende Untersuchung der Depot-Neuroleptika Perphenazin Onanthat und Fluspirilen.

The clinical profile and side-effects of perphenazin-enanthate and fluspirilene were compared in 45 female chronic schizophrenic patients. 100 mg perphenazin-enanthate fortnightly or 8 mg fluspirilene weekly were administered. During the four months' period the psychopathological and somatic symptoms were evaluated by means of the AMP-system and the self-evaluation scale PD-S (v. Zerssen). A covariance analysis was carried out covering 12 AMP syndromes and 6 PD-S factors. The antipsychotic effect of both drugs was similar concerning the paranoid, the hallucinatory-desintegrative and the catatonic syndromes. A significant difference with regard to perphenazin-enanthate was found in the AMP-syndromes of hostility, hypochondria, and autonomic symptoms. Neither drug induced any depression. In the self-rating scale, the factors anxiousness and depressivity were also significantly lower in the perphenazin-enanthate regime. The patients under perphenazin-enanthate required a smaller amount of antiparkinsonian drugs. The more pronounced sedative effect of perphenazin-enanthate can be recommended in hostile and restless schizophrenic patients, whereas fluspirilene should be given to inactive autistic patients.

Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.

Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.