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1.
Metab Brain Dis ; 34(6): 1679-1687, 2019 12.
Article En | MEDLINE | ID: mdl-31422510

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12 months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91 ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12 months more women than men had hyperprolactinemia (defined as more than 20 ng/ml for males, and as more than 25 ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12 months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.


Flupenthixol/analogs & derivatives , Hyperprolactinemia/chemically induced , Propafenone/blood , Schizophrenia/drug therapy , Tranquilizing Agents/therapeutic use , Adolescent , Adult , Age Factors , Female , Flupenthixol/adverse effects , Flupenthixol/therapeutic use , Humans , Male , Schizophrenia/blood , Sex Factors , Tranquilizing Agents/adverse effects , Treatment Outcome , Young Adult
2.
Psychopharmacology (Berl) ; 236(11): 3081-3092, 2019 Nov.
Article En | MEDLINE | ID: mdl-31300829

RATIONALE: The licensed dose range for the long-acting injectable antipsychotic flupentixol decanoate (Depixol®) in the treatment of schizophrenia is very broad. This provides little useful direction to prescribers and may ultimately result in patients receiving unnecessarily high doses. OBJECTIVES: We aimed to estimate the effect of dose of flupentixol decanoate on relapse rates in schizophrenia and on tolerability by expanding on an earlier review and including non-RCT and German-language studies, as well as using pharmacokinetic and pharmacodynamic data to offer guidance on dosing. METHODS: A literature review using EMBASE, Medline, PsycINFO and PubMed was conducted. Treatment success rates at 6 months were extracted or extrapolated from the studies and plotted against dose to estimate a dose-response curve. RESULTS: Data from 16 studies (n = 514) allowed estimation of a dose-response curve which rises steeply between the chosen placebo anchor (25% success rate) and 10 mg every 2 weeks before reaching a maximum between 20 and 40 mg every 2 weeks (80-95% success rates). Extrapyramidal side effects (EPSEs) were frequently seen (12-71% of participants) in that dose range. Two -weekly injections seem to provide the highest trough plasma concentration per dose administered and the lowest peak-to-trough concentration ratio. Plasma concentration varied up to 5-fold among individuals receiving the same dose. CONCLUSIONS: The optimal dose of flupentixol decanoate is likely to be between 20 mg and 40 mg every 2 weeks although higher doses may be required in some individuals owing to variation in drug handling. Doses of flupentixol should be individually established in the range of 10 to 40 mg every 2 weeks according to response and tolerability.


Dopamine Antagonists/administration & dosage , Flupenthixol/analogs & derivatives , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Antipsychotic Agents/administration & dosage , Delayed-Action Preparations/administration & dosage , Dose-Response Relationship, Drug , Female , Flupenthixol/administration & dosage , Humans , Male , Middle Aged , Schizophrenia/diagnosis , Treatment Outcome
3.
Schizophr Res ; 206: 394-399, 2019 04.
Article En | MEDLINE | ID: mdl-30385130

BACKGROUND: While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised. AIMS: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.


Antipsychotic Agents/therapeutic use , Cognition , Flupenthixol/analogs & derivatives , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adolescent , Adult , Female , Flupenthixol/therapeutic use , Health Personnel/psychology , Humans , Longitudinal Studies , Male , Psychiatric Status Rating Scales , Psychotic Disorders/psychology , Quality of Life , Schizophrenic Psychology , Time Factors , Treatment Outcome , Young Adult
4.
Schizophr Res ; 206: 171-176, 2019 04.
Article En | MEDLINE | ID: mdl-30503765

BACKGROUND: Treatment-emergent weight gain is associated with antipsychotic efficacy in schizophrenia patients treated with clozapine and olanzapine. However, few studies have investigated this relationship in first-episode patients treated with other antipsychotics, in particular those with a lower obesogenic potential. Aim To investigate the relationships between weight gain and associated metabolic changes with psychopathology improvement in relation to age, sex, ethnicity, substance use, treatment duration and antipsychotic dose in first-episode schizophrenia spectrum disorder patients. METHODS: This single site cohort study included 106 minimally treated or antipsychotic-naive patients treated with flupenthixol decanoate over 12 months. Psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) and BMI, fasting blood lipids and glucose were assessed at regular intervals. Linear regression models were constructed to determine the effects of socio-demographic, clinical and metabolic factors as predictors of change in total PANSS score and factor-derived domains. RESULTS: BMI change scores were inversely correlated with change in PANSS total (R = -0.25; p = 0.011), positive (R = -0.23; p = 0.019), depressive anxiety (R = -0.21; p = 0.031) and disorganized symptoms (R = -0.32; p < 0.001). Linear regression analysis showed that increased BMI and treatment duration both predicted improvement in global psychopathology and disorganized symptoms independent of age, sex, ethnicity, substance use, co-medication with antidepressants and/or anticholinergics, as well as the dose and duration of antipsychotic exposure. CONCLUSIONS: Our findings suggest that the relationship between treatment-emergent weight gain and psychopathology improvement is not limited to patients treated with antipsychotics most associated with weight gain, and is not confounded by treatment duration and dose.


Dopamine Antagonists/pharmacology , Outcome Assessment, Health Care , Schizophrenia/blood , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Weight Gain , Adult , Body Mass Index , Dopamine Antagonists/administration & dosage , Dopamine Antagonists/adverse effects , Female , Flupenthixol/analogs & derivatives , Flupenthixol/pharmacology , Humans , Longitudinal Studies , Male , Severity of Illness Index , Weight Gain/drug effects , Young Adult
6.
Psychiatry Res ; 262: 141-148, 2018 04.
Article En | MEDLINE | ID: mdl-29448178

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies.


Adult Survivors of Child Adverse Events/psychology , Antipsychotic Agents/therapeutic use , Flupenthixol/analogs & derivatives , Gene-Environment Interaction , Matrix Metalloproteinase 9/genetics , Schizophrenia/drug therapy , Schizophrenia/genetics , Adolescent , Adult , Female , Flupenthixol/therapeutic use , Haplotypes , Humans , Male , Polymorphism, Genetic , Treatment Outcome , Young Adult
7.
Psychol Med ; 47(12): 2187-2196, 2017 Sep.
Article En | MEDLINE | ID: mdl-28347393

BACKGROUND: Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.


Antipsychotic Agents/pharmacology , Cerebral Cortex , Flupenthixol/analogs & derivatives , Gray Matter , Psychotic Disorders , Schizophrenia , White Matter , Adult , Antipsychotic Agents/administration & dosage , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/drug effects , Cerebral Cortex/pathology , Delayed-Action Preparations , Female , Flupenthixol/administration & dosage , Flupenthixol/pharmacology , Gray Matter/diagnostic imaging , Gray Matter/drug effects , Gray Matter/pathology , Humans , Magnetic Resonance Imaging , Male , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Psychotic Disorders/pathology , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy , Schizophrenia/pathology , Treatment Outcome , White Matter/diagnostic imaging , White Matter/drug effects , White Matter/pathology , Young Adult
8.
Schizophr Res ; 188: 144-150, 2017 10.
Article En | MEDLINE | ID: mdl-28130002

BACKGROUND: Neurological soft signs (NSS) are proposed to represent both state- and trait-related features of schizophrenia. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.


Antipsychotic Agents/administration & dosage , Cognition/drug effects , Psychotic Disorders/drug therapy , Psychotic Disorders/physiopathology , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Female , Flupenthixol/administration & dosage , Flupenthixol/analogs & derivatives , Humans , Interview, Psychological , Linear Models , Longitudinal Studies , Male , Memory, Short-Term/drug effects , Motor Activity/drug effects , Neurologic Examination , Psychiatric Status Rating Scales , Psychotic Disorders/psychology , Schizophrenic Psychology , Severity of Illness Index , Treatment Outcome , Young Adult
9.
Pharmacogenomics ; 18(2): 105-120, 2017 Jan.
Article En | MEDLINE | ID: mdl-27992301

AIM: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103). RESULTS: Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4). CONCLUSION: This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.


Antipsychotic Agents/therapeutic use , Chromosome Mapping/methods , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide/genetics , Schizophrenia/drug therapy , Schizophrenia/genetics , Adolescent , Adult , Cohort Studies , Female , Flupenthixol/analogs & derivatives , Flupenthixol/therapeutic use , Genetic Variation/genetics , Humans , Male , Schizophrenia/epidemiology , South Africa/epidemiology , Treatment Outcome , Young Adult
10.
Early Interv Psychiatry ; 10(1): 54-62, 2016 Feb.
Article En | MEDLINE | ID: mdl-24690088

AIM: To assess the feasibility and effectiveness of depot antipsychotic (flupenthixol decanoate) combined with an assertive monitoring programme (AMP) in first-episode schizophrenia. METHODS: This was a prospective, non-comparative, longitudinal study conducted over 12 months assessing patient acceptance, adherence, outcome in domains of psychopathology, functionality and quality of life, and tolerability. RESULTS: Of 207 participants, 149 (72%) completed 12 months of treatment. Acceptance of and adherence to depot was good. Treatment response was achieved by 170 (82%) participants and remission by 124 (60%). Thirty-three (19%) responders relapsed and 10 (5%) participants met a priori criteria for treatment resistance. Treatment was generally well tolerated. CONCLUSIONS: Combination of depot antipsychotic with an AMP may be an effective and safe intervention in early phases of schizophrenia, and may be particularly suitable for resource-constrained settings.


Community Mental Health Services/methods , Flupenthixol/analogs & derivatives , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Antipsychotic Agents/therapeutic use , Delayed-Action Preparations/adverse effects , Delayed-Action Preparations/therapeutic use , Developing Countries , Female , Flupenthixol/adverse effects , Flupenthixol/therapeutic use , Humans , Male , Medication Adherence , Patient Acceptance of Health Care , Quality of Life , Treatment Outcome
11.
Psychiatry Res ; 233(2): 186-93, 2015 Aug 30.
Article En | MEDLINE | ID: mdl-26184461

We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication.


Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Body Mass Index , Brain/drug effects , Brain/physiopathology , Eating/drug effects , Eating/physiology , Flupenthixol/analogs & derivatives , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Risperidone/adverse effects , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Adolescent , Adult , Delayed-Action Preparations , Double-Blind Method , Female , Flupenthixol/administration & dosage , Flupenthixol/adverse effects , Humans , Injections, Intramuscular , Male , Middle Aged , Risperidone/administration & dosage , South Africa , Young Adult
12.
Neurosci Lett ; 600: 226-31, 2015 Jul 23.
Article En | MEDLINE | ID: mdl-26101827

We describe the profile of NSS across the one-year course of schizophrenia in 84 Nigerian first-episode patients. They were assessed at baseline and 3 monthly for 12 months using the Neurological Evaluation Scale and the Positive and Negative Syndrome Scale (PANSS), and treated with flupenthixol decanoate. The pattern of NSS total and sub-category scores obtained from repeated measurements were investigated for responders (≥ 50% reduction of baseline PANSS scores) and non-responders using the method of repeated measures analysis of variance. Trait-like features of NSS categories were quantified using intraclass correlation coefficients (ICCs). NSS were present in 96.4% of the patients at baseline (mean 21.5 ± 11.1). The motor-sequencing sub-category was found unrelated to changes in schizophrenia psychopathology with treatment (positive, r=0.19, p=0.136., negative, r=0.12, p=0.350; disorganization, r=0.16, p=0.245; overall, r=0.20, p=0.112). Regardless of decrements in psychopathology, motor-sequencing scores remained relatively unchanged across the course of the disease (main effects: 'responders' F=2.44, p=0.930, 'poor responders' F=0.27, p=0.764, entire sample F=1.87, p=0.160). ICC was "substantial" at 0.8 (95% C.I=0.6-0.9). Only the motor-sequencing NSS appear to be trait marker of schizophrenia in this sample. Other NSS seem to reflect symptomatic states of the disorder.


Schizophrenia/diagnosis , Adult , Antipsychotic Agents/therapeutic use , Black People , Female , Flupenthixol/analogs & derivatives , Flupenthixol/therapeutic use , Humans , Male , Neurologic Examination , Psychiatric Status Rating Scales , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Young Adult
13.
Hum Psychopharmacol ; 30(3): 173-82, 2015 May.
Article En | MEDLINE | ID: mdl-25758549

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Results are consistent with a lower rate of refractoriness to treatment in first-episode schizophrenia compared with multi-episode samples.


Antipsychotic Agents/therapeutic use , Flupenthixol/analogs & derivatives , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adolescent , Adult , Age Factors , Body Mass Index , Cohort Studies , Female , Flupenthixol/therapeutic use , Humans , Longitudinal Studies , Male , Psychotic Disorders/physiopathology , Quality of Life , Schizophrenia/physiopathology , Treatment Outcome , Young Adult
14.
Eur Psychiatry ; 30(2): 277-83, 2015 Feb.
Article En | MEDLINE | ID: mdl-25577186

OBJECTIVES: To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects. METHODS: We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months. RESULTS: Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P<.0001), waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P=.008). The only significant predictor of BMI increase was non-substance abuse (P=.002). CONCLUSIONS: The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.


Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Blood Glucose/metabolism , Body Mass Index , Cholesterol/blood , Flupenthixol/analogs & derivatives , Metabolic Syndrome/chemically induced , Schizophrenia/drug therapy , Triglycerides/blood , Adult , Biomarkers/blood , Cohort Studies , Female , Flupenthixol/administration & dosage , Flupenthixol/adverse effects , Humans , Male , Metabolic Syndrome/blood , Metabolome , Schizophrenia/blood , South Africa , Weight Gain/drug effects
15.
Cochrane Database Syst Rev ; (6): CD001470, 2014 Jun 10.
Article En | MEDLINE | ID: mdl-24915451

BACKGROUND: Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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). AUTHORS' CONCLUSIONS: 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.


Flupenthixol/analogs & derivatives , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Tranquilizing Agents/therapeutic use , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/therapeutic use , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/therapeutic use , Flupenthixol/administration & dosage , Flupenthixol/therapeutic use , Humans , Randomized Controlled Trials as Topic , Tranquilizing Agents/administration & dosage
16.
Eur J Health Econ ; 15(2): 133-42, 2014 Mar.
Article En | MEDLINE | ID: mdl-23420082

We use longitudinal patient-level data from a German sickness fund with 7.26 million insured in a Markov-simulation model to assess the cost-effectiveness of long-acting injectable risperidone (LAI-RIS) compared with long-acting injectable flupentixol (LAI-FLX) in the long-term management of schizophrenia. We simulate treatment costs from the payer's perspective, hospitalization, the probability to be prescribed co-medication, and treatment discontinuation over a 2-year time horizon. Model inputs were derived from 935 patients hospitalized with schizophrenia between 2005 and 2008 who received either LAI-RIS or LAI-FLX for at least 1 month. After 2 years, 89.4% (95.8%) of patients who were initiated on LAI-RIS (LAI-FLX) discontinued the initial regimen. The number of days spent in hospital per month and patient was slightly lower with LAI-RIS (1.08 vs. 1.28 days, p<0.001). The proportion of patients receiving side-effect co-medication was lower with LAI-RIS (8.3 vs. 15.0% per month, p<0.001). Mean total costs of treatment per patient and month were 1,015 € under LAI-RIS and 395 € under LAI-FLX, resulting in an ICER of 3,088 € (95% CI [-913 €; 3,551 €]) for an avoided hospital day per patient and month in the base case scenario with a 15.1% probability of LAI-FLX being the dominant treatment strategy. Cost differences were mainly attributable to the higher drug costs of LAI-RIS. The effectiveness of LAI-RIS in preventing hospital days appears to be similar to LAI-FLX, with a slight superiority in side-effect and switching rates. This comes at the cost of substantially higher treatment expenses. From a decision-maker's point of view, the use of health insurance data as a source of input for decision models appears to be a reasonable alternative to models driven by clinical data only.


Antipsychotic Agents/economics , Flupenthixol/analogs & derivatives , Risperidone/economics , Schizophrenia/drug therapy , Adult , Antipsychotic Agents/therapeutic use , Cost-Benefit Analysis , Delayed-Action Preparations , Female , Flupenthixol/economics , Flupenthixol/therapeutic use , Hospitalization/economics , Humans , Male , Markov Chains , Middle Aged , Models, Econometric , Risperidone/therapeutic use
18.
Int J Prison Health ; 4(2): 96-103, 2008.
Article En | MEDLINE | ID: mdl-18464063

In past years, Zuclopenthixolacetate as well as Flupentixoldecanoate have each proven to be reliable and efficient in the treatment of schizophrenic psychoses. In a specially implemented psychiatric treatment unit (PTU) we administered a high-dose depot neuroleptic combination therapy initially consisting of both substances to seriously ill schizophrenic prisoners who exhibited highly aggressive behaviour (N=20). We initially used both antipsychotics at the same time as a simple regimen in order to restore the prisoners' health to enable them to return to their home prisons. A single coercive intervention was performed in 14 out of 20 prisoners which was followed by a second one in two cases according to Article 101 of the German Code of Criminal Procedure. On average, prisoners needed a treatment course of 30.4 days. Within this time PANSS global scores were reduced by approximately 40%. Side effects occurring as a consequence of neuroleptic treatment were negligible and could be dealt with.


Aggression/drug effects , Antipsychotic Agents/administration & dosage , Clopenthixol/analogs & derivatives , Flupenthixol/analogs & derivatives , Prisoners , Schizophrenia, Paranoid/drug therapy , Adult , Antipsychotic Agents/adverse effects , Clopenthixol/administration & dosage , Clopenthixol/adverse effects , Delayed-Action Preparations , Drug Therapy, Combination , Emergency Services, Psychiatric , Flupenthixol/administration & dosage , Flupenthixol/adverse effects , Humans , Pilot Projects , Retrospective Studies , Treatment Outcome
19.
Psychiatr Prax ; 34(6): 289-91, 2007 Sep.
Article De | MEDLINE | ID: mdl-17806015

OBJECTIVE: The reduction of the frequency of rehospitalisation is important for improving the outcomes for patients with schizophrenia. METHODS: This study compares the rate of rehospitalisation between patients with antipsychotics in depot-form (n = 77) and oral second-generation antipsychotics (SGA) (n = 156). RESULTS: Patients with antipsychotics in depot-form had lower risk of rehospitalisation than with SGAs in oral-form after 24 months (p = 0.027) and 36 months (p = 0.018) (Kaplan-Meyer survival analysis, Log-Rank). Long intervals between two hospitalisations were found for flupentixol depot and clozapine. CONCLUSIONS: Antipsychotics in depot-form require and active and close outpatient treatment, which may account for long intervals between hospitalisation improved outcomes for patients with schizophrenia.


Antipsychotic Agents/administration & dosage , Patient Readmission , Schizophrenia/drug therapy , Schizophrenic Psychology , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Antipsychotic Agents/adverse effects , Clozapine/administration & dosage , Delayed-Action Preparations , Female , Flupenthixol/administration & dosage , Flupenthixol/analogs & derivatives , Hospitals, Psychiatric/statistics & numerical data , Humans , Male , Middle Aged , Patient Readmission/statistics & numerical data , Retrospective Studies , Schizophrenia/diagnosis , Schizophrenia/epidemiology , Treatment Outcome
20.
Alcohol Alcohol ; 42(2): 108-12, 2007.
Article En | MEDLINE | ID: mdl-17255151

AIMS: Self-help groups such as Alcoholics Anonymous (AA) are widely recommended for aftercare of alcohol-dependent persons, even though scientific knowledge of its effectiveness is inconsistent. The aim of the present analysis was to elucidate whether persons attending AA groups regularly after detoxification have lower relapse rates within 1 year, compared to persons without self-help group attendance. METHODS: Data for the present analysis were derived from the placebo-group of a multi-centre study in Germany (Wiesbeck et al., 2001). Patients were free to choose either self-help group attendance (N = 50) or no support (N = 28). RESULTS: After 1-month of follow-up, there was a lower relapse rate in patients attending a self-help group as compared to the control group, a difference, however, that leveled off during the following months. Moreover, relapse rates did not differ significantly at any point of time between both groups. Levels of social functioning improved in both groups over 1 year. CONCLUSIONS: The present study was unable to show an advantage of self-help group attendance in reducing relapses compared to the control group.


Alcoholics Anonymous , Alcoholism/rehabilitation , Temperance/psychology , Adult , Alcoholism/psychology , Antipsychotic Agents/therapeutic use , Female , Flupenthixol/analogs & derivatives , Flupenthixol/therapeutic use , Follow-Up Studies , Germany , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Outcome Assessment, Health Care , Patient Dropouts/psychology , Secondary Prevention
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