flupenthixol-decanoate and Psychotic-Disorders

Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia.. To evaluate the effects of flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes.. We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.. All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought.. Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies.. The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence).. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Flupenthixol; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Tranquilizing Agents

Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment.. To evaluate the effects flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes.. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). The references of all identified trials were inspected for more studies and the first author of each included trial and relevant pharmaceutical companies were contacted.. All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared to placebo or other antipsychotic drugs. All clinically relevant outcomes were sought.. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality.. No trials compared flupenthixol decanoate to placebo. One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). There were no clear differences between the two preparations. When flupenthixol decanoate was compared to other depot preparations, there were no differences between depots for outcomes such as death, global impression, relapse (OR 1.16 CI 0.7-1.9) or leaving the study early (OR 1.00 CI 0.6-1.7). Two small studies suggest that flupenthixol decanoate is responsible for less movement disorders than other depot antipsychotic drugs (OR 0.23 CI 0.08-0.7, NNT 5). This finding did not hold for specific side effects, such as tremor (OR 1.2 CI 0.3-4) and tardive dyskinesia (OR 1.60 CI 0.4-6). Two trials comparing high doses of flupenthixol decanoate to the standard approximately 40mg per injection reported no significant difference for the outcome of relapse (OR 0.32 CI 0.09-1.2). One small (n=59) trial comparing a very low dose of flupenthixol decanoate ( approximately 6 mg/IM) to a very low dose approximately 9 mg per injection also reported no difference in relapse rates (OR 0.3 CI 0.1-1.1).. 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.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Flupenthixol; Humans; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised.. We assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic.. This single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models.. There was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight.. Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

Topics: Adolescent; Adult; Antipsychotic Agents; Cognition; Female; Flupenthixol; Health Personnel; Humans; Longitudinal Studies; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome; Young Adult

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.. We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).. Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.. Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

Topics: Adult; Antipsychotic Agents; Cerebral Cortex; Delayed-Action Preparations; Female; Flupenthixol; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Psychotic Disorders; Schizophrenia; Treatment Outcome; White Matter; Young Adult

Neurological soft signs (NSS) are proposed to represent both state- and trait-related features of schizophrenia.. We assessed the course of NSS with the Neurological Evaluation Scale (NES) over 12months of standardised treatment in 126 patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder, and evaluated their state- and trait-related associations with psychopathology, functionality, cognition and antipsychotic treatment. We considered change scores from baseline to be state-related and endpoint scores to be trait-related.. Significant effects for time were recorded for all NSS domains. For state-related change-scores greater improvements in sensory integration were predicted by more improvement in working memory (p=0.01); greater improvements in motor sequencing scores were predicted by more improvement in working memory (p=0.005) and functionality (p=0.005); and greater improvements in NES Total score were predicted by more improvement in disorganised symptoms (p=0.02). There were more substantial associations between trait-related endpoint scores than for state-related change scores. For endpoint scores lower composite cognitive score predicted poorer sensory integration (p=0.001); higher Parkinsonism score predicted poorer motor co-ordination (p=0.0001); lower composite cognitive score (p=0.001) and higher Parkinsonism score (p=0.005) predicted poorer motor sequencing; higher Parkinsonism score (p=0.0001) and disorganised symptoms (p=0.04), and lower composite cognitive score (p=0.0007) predicted higher NES total score.. NSS improved with treatment, but were weakly associated with improvements in psychopathology. Studies investigating NSS as trait-markers should ensure that patients have been optimally treated at the time of testing, and should take possible effects of extrapyramidal symptoms into account.

Topics: Antipsychotic Agents; Cognition; Female; Flupenthixol; Humans; Interview, Psychological; Linear Models; Longitudinal Studies; Male; Memory, Short-Term; Motor Activity; Neurologic Examination; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome; Young Adult

The goals of this study were to (i) estimate the rate of non-response to first-line treatment in first-episode schizophrenia, (ii) evaluate other outcomes associated with symptom non-response and (iii) identify demographic, baseline clinical and early treatment response predictors of non-response.. This was a single-site, longitudinal cohort study assessing the effects of treatment with flupenthixol decanoate according to a standardised protocol over 12 months in patients with schizophrenia, schizophreniform and schizo-affective disorders.. Of 126 patients who received at least one dose of study medication, 84 (67%) completed the study. Fifteen (12%) met our predefined criteria for non-response. Non-responders were younger and at baseline had more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS) and lower body mass index. At endpoint, the non-responders were characterised by higher levels of symptomatology in all domains, poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and lower body mass index. The strongest predictors of non-response were more prominent baseline NSS and poor early (7 weeks) treatment response.. Results are consistent with a lower rate of refractoriness to treatment in first-episode schizophrenia compared with multi-episode samples.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Body Mass Index; Cohort Studies; Female; Flupenthixol; Humans; Longitudinal Studies; Male; Psychotic Disorders; Quality of Life; Schizophrenia; Treatment Outcome; Young Adult

Two cases of agranulocytosis occurring after addition of a butyrophenone to a course of phenothiazine treatment are reported and possible mechanisms for this interaction are discussed.

Topics: Agranulocytosis; Antipsychotic Agents; Chlorpromazine; Clomipramine; Depressive Disorder; Dose-Response Relationship, Drug; Droperidol; Drug Therapy, Combination; Female; Flupenthixol; Fluphenazine; Humans; Long-Term Care; Male; Middle Aged; Paranoid Disorders; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Humans; Middle Aged; Psychotic Disorders; Schizophrenia

The present open study was undertaken to evaluate the therapeutic efficacy and side-effects of flupenthixol, a thioxanthene derivative in the treatment of schizoaffective psychosis. A total of twenty in-patients, selected according to specific research criteria were treated with flupenthixol (20 mg to 60 mg i.m. q.2.weeks) for a period of 6 months. During the course of the study, a detailed battery of psychiatric rating scales was completed prior to the commencement of the treatment and at regular intervals thereafter. Additionally, detailed physical examinations and laboratory tests were also carried out at regular intervals. Results show that fifteen patients improved significantly, two patients remained unchanged while three patients deteriorated and were discontinued. Adverse effects were minimal and limited to tremor and akathisia. The present study highlights the usefulness of flupenthixol as a monotherapy in the management of schizoaffective psychosis.

Topics: Adult; Drug Evaluation; Female; Flupenthixol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Thioxanthenes