Antipsychotic polypharmacy reduction versus polypharmacy continuation for people with schizophrenia.
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ABSTRACT:
SUBMITTER: Bighelli I
PROVIDER: S-EPMC9427025 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Antipsychotic polypharmacy reduction versus polypharmacy continuation for people with schizophrenia.
Bighelli Irene I Rodolico Alessandro A Siafis Spyridon S Samara Myrto T MT Hansen Wulf-Peter WP Salomone Salvatore S Aguglia Eugenio E Cutrufelli Pierfelice P Bauer Ingrid I Baeckers Lio L Leucht Stefan S
The Cochrane database of systematic reviews 20220830
<h4>Background</h4>In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, but must be done carefully, in order to maintain efficacy.<h4>Objectives</h4>To examine the effects and safety of reducing antipsychotic polypharm ...[more]
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| S-EPMC9685497 | biostudies-literature
Project description:There is conflicting evidence on the association between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. We conducted a review of published systematic reviews to evaluate evidence on the association between metabolic syndrome (diabetes, hypertension, and hyperlipidaemia) and exposure to antipsychotic polypharmacy in schizophrenia.We searched five electronic databases, complemented by reference screening, to find systematic reviews that investigated the association of antipsychotic polypharmacy in schizophrenia with hypertension, diabetes, or hyperlipidaemia. Selection of reviews, data extraction and review quality were conducted independently by two people and disagreements resolved by discussion. Results were synthesised narratively.We included 12 systematic reviews, which reported heterogeneous results, mostly with narrative syntheses and without pooled data. The evidence was rated as low quality. There was some indication of a possible protective effect of drug combinations including aripiprazole for diabetes and hyperlipidaemias, compared to other combinations and/or monotherapy. Only one review reported the association between APP and hypertension. The most frequently reported combinations of medication included clozapine, possibly representing a sample of patients with treatment resistant illness. No included review reported results separately by setting (primary or secondary care).Further robust studies are needed to elucidate the possible protective effect of aripiprazole. Long-term prospective studies are required for accurate appraisal of diabetes risk, hypertension and hyperlipidaemia in patients exposed to antipsychotic polypharmacy.
| S-EPMC6122457 | biostudies-other
Project description:INTRODUCTION:Antipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefits outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes. METHODS AND ANALYSIS:This is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a five-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identified by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to finish in June 2022. ETHICS AND DISSEMINATION:Ethical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public. TRIAL REGISTRATION NUMBER:ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results.
| S-EPMC6887002 | biostudies-literature
Project description:ImportanceThe effectiveness of antipsychotic polypharmacy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical well-being.ObjectiveTo study the association of specific antipsychotic combinations with psychiatric rehospitalization.Design, setting, and participantsIn this nationwide cohort study, the risk of psychiatric rehospitalization was used as a marker for relapse among 62 250 patients with schizophrenia during the use of 29 different antipsychotic monotherapy and polypharmacy types between January 1, 1996, and December 31, 2015, in a comprehensive, nationwide cohort in Finland. We conducted analysis of the data from April 24 to June 15, 2018. Rehospitalization risks were investigated by using within-individual analyses to minimize selection bias.Main outcomes and measuresHazard ratio (HR) for psychiatric rehospitalization during use of polypharmacy vs during monotherapy within the same individual.ResultsIn the total cohort, including 62 250 patients, 31 257 individuals (50.2%) were men, and the median age was 45.6 (interquartile range, 34.6-57.9) years. The clozapine plus aripiprazole combination was associated with the lowest risk of psychiatric rehospitalization in the total cohort, being superior to clozapine, the monotherapy associated with the best outcomes, with a difference of 14% (HR, 0.86; 95% CI, 0.79-0.94) in the analysis including all polypharmacy periods, and 18% in the conservatively defined polypharmacy analysis excluding periods shorter than 90 days (HR, 0.82; 95% CI, 0.75-0.89; P < .001). Among patients with their first episode of schizophrenia, these differences between clozapine plus aripiprazole vs clozapine monotherapy were greater (difference, 22%; HR, 0.78; 95% CI, 0.63-0.96 in the analysis including all polypharmacy periods, and difference, 23%; HR, 0.77; 95% CI, 0.63-0.95 in the conservatively defined polypharmacy analysis). At the aggregate level, any antipsychotic polypharmacy was associated with a 7% to 13% lower risk of psychiatric rehospitalization compared with any monotherapy (ranging from HR, 0.87; 95% CI, 0.85-0.88, to HR, 0.93; 95% CI, 0.91-0.95; P < .001). Clozapine was the only monotherapy among the 10 best treatments. Results on all-cause and somatic hospitalization, mortality, and other sensitivity analyses were in line with the primary outcomes.Conclusions and relevanceCombining aripiprazole with clozapine was associated with the lowest risk of rehospitalization, indicating that certain types of polypharmacy may be feasible in the treatment of schizophrenia. Because add-on treatments are started when monotherapy is no longer sufficient to control for worsening of symptoms, it is likely that the effect sizes for polypharmacy are underestimates. Although the results do not indicate that all types of polypharmacy are beneficial, the current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia.
| S-EPMC6495354 | biostudies-literature
Project description:BACKGROUND:Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. OBJECTIVES:To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA:We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS:We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data. MAIN RESULTS:We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). AUTHORS' CONCLUSIONS:Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.
| S-EPMC7052752 | biostudies-literature
Project description:ObjectiveAlthough U.K. and international guidelines recommend monotherapy, antipsychotic polypharmacy among patients with serious mental illness is common in clinical practice. However, empirical evidence on its effectiveness is scarce. Therefore, the authors estimated the effectiveness of antipsychotic polypharmacy relative to monotherapy in terms of health care utilization and mortality.MethodsPrimary care data from Clinical Practice Research Datalink, hospital data from Hospital Episode Statistics, and mortality data from the Office of National Statistics were linked to compile a cohort of patients with serious mental illness in England from 2000 to 2014. The antipsychotic prescribing profile of 17,255 adults who had at least one antipsychotic drug record during the period of observation was constructed from primary care medication records. Survival analysis models were estimated to identify the effect of antipsychotic polypharmacy on the time to first occurrence of each of three outcomes: unplanned hospital admissions (all cause), emergency department (ED) visits, and mortality.ResultsRelative to monotherapy, antipsychotic polypharmacy was not associated with increased risk of unplanned hospital admission (hazard ratio [HR]=1.14; 95% confidence interval [CI]=0.98-1.32), ED visit (HR=0.95; 95% CI=0.80-1.14), or death (HR=1.02; 95% CI=0.76-1.37). Relative to not receiving antipsychotic medication, monotherapy was associated with a reduced hazard of unplanned admissions to the hospital and ED visits, but it had no effect on mortality.ConclusionsThe study results support current guidelines for antipsychotic monotherapy in routine clinical practice. However, they also suggest that when clinicians have deemed antipsychotic polypharmacy necessary, health care utilization and mortality are not affected.
| S-EPMC6890489 | biostudies-literature
Project description:ObjectiveAlthough antipsychotic polypharmacy is widely used in the pharmacotherapy of schizophrenia, its effectiveness is controversial. In particular, clinicians tend to avoid switching to monotherapy in patients who have been prescribed polypharmacy. In the present study, the authors investigate whether there is difference in time to discontinuation of antipsychotics between patients on previous monotherapy or polypharmacy.MethodsPooled analysis was conducted on two 24-week, multicenter, open-label, non-comparative studies that were originally designed to investigate the effectiveness of switching to paliperidone extended-release (ER) in patients with schizophrenia. Patients were divided into two groups according to previously prescribed antipsychotics, that is, to a polypharmacy group or a monotherapy group. The primary outcome measure was time to discontinuation of paliperidone ER. In addition, the authors sought to identify clinical variables that influence time to discontinuation.ResultsBefore switching to paliperidone ER, 535 of 673 (79.5%) patients were prescribed antipsychotic monotherapy, and the remaining 138 (20.5%) patients were prescribed antipsychotic polypharmacy. No significant differences in time to discontinuation of paliperidone ER were observed between the polypharmacy and monotherapy groups. Personal and social performance scale score was the only factor found to influence time to discontinuation of paliperidone ER. No differences in psychopathology or adverse effects were found between the monotherapy and polypharmacy groups.ConclusionOur results suggest that number of antipsychotics prescribed before switching to monotherapy does not influence clinical prognosis in patients with schizophrenia.
| S-EPMC3897764 | biostudies-literature
Project description:BackgroundAntipsychotic polypharmacy (APP) remains common despite guideline recommendations to minimize combinations, except after repeated antipsychotic monotherapy trials. This study aimed to assess APP and its associated factors among schizophrenia patients at comprehensive specialized hospitals in Northwest Ethiopia.MethodsAn institutional-based cross-sectional study was conducted among 422 schizophrenia patients at selected hospitals in Ethiopia from June to August 2022. The data were collected using a semi-structured questionnaire. Study participants were enrolled using systematic random sampling. Data entry and analysis were done with Epi-data version 4.6.1 and SPSS version 24, respectively. APP was determined by reviewing the number of medications based on relevant evidence. A multivariable logistic regression model was fitted to identify APP factors. Variables with a p-value of < 0.05 at a 95% confidence interval were considered statistically significant.ResultsFrom a total of 430 approached samples, 422 (98.1% response rate) eligible patients were included in the study. An overall APP prevalence was 22.7% (95% CI: 19-27). Duration of illness (AOR = 2.88; 95% CI: 1.49, 5.59); duration of treatment (AOR = 3.79; 95% CI: 1.05, 13.62); number of admissions (AOR = 4.93; 95% CI: 2.52, 9.64); and substance use (AOR = 2.58; 95% CI: 1.49, 4.47) were significantly associated with APP.Conclusion and recommendationIn this study, APP was recorded in a considerable number of patients. Patients with a longer duration of illness and treatment, frequent admissions, and substance users need critical follow-up to minimize antipsychotic medication use.
| S-EPMC10424862 | biostudies-literature
Project description:BackgroundAntipsychotic medication can reduce psychotic symptoms and risk of relapse in people with schizophrenia and related disorders, but it is not always effective and adverse effects can be significant. We know little of patients' views about continuing or discontinuing antipsychotic treatment.AimsTo explore the views of people with schizophrenia and other psychotic disorders about continuing their antipsychotic medication or attempting to reduce or discontinue this medication with clinical support.MethodsWe collected quantitative and qualitative data by conducting semi-structured interviews in London, UK. Factors predicting a desire to discontinue medication were explored. Content analysis of qualitative data was undertaken.ResultsWe interviewed 269 participants. 33% (95% CI, 27 to 39%) were content with taking long-term antipsychotic medication. Others reported they took it reluctantly (19%), accepted it on a temporary basis (24%) or actively disliked it (18%). 31% (95% CI, 25 to 37%) said they would like to try to stop medication with professional support, and 45% (95% CI, 39 to 51%) wanted the opportunity to reduce medication. People who wanted to discontinue had more negative attitudes towards the medication but were otherwise similar to other participants. Wanting to stop or reduce medication was motivated mainly by adverse effects and health concerns. Professional support was identified as potentially helpful to achieve reduction.ConclusionsThis large study reveals that patients are commonly unhappy about the idea of taking antipsychotics on a continuing or life-long basis. Professional support for people who want to try to reduce or stop medication is valued.
| S-EPMC8925064 | biostudies-literature
Project description:BackgroundReal world evidence about antipsychotics focuses on rehospitalization. Modeling the time course of pharmacotherapy would show patients' adherence to medications and physicians' adherence to medication guidelines. We aimed to calculate the cumulative time spent in second generation antipsychotics (SGAs), gaps, antipsychotic polypharmacy, and clozapine in discharged schizophrenia patients.MethodsHospitalization and pharmacy dispensing data from 2008-2018 in Manitoba, Saskatchewan, and British Columbia were linked and an electronic cohort (N = 2,997) was created (mean follow-up: 49 months, SD = 38). Cohort members were required to have a minimum of 6 weeks medicated with aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone.ResultsThe multistate model predicted that schizophrenia patients accumulated 44 months in SGA monotherapy, 4 months in polypharmacy, 11 months in medication gaps and 17 days in clozapine over a 5-year period. The majority of transitions were between SGA and medication gap. Accumulated time in medication gaps was seven times as much as in clozapine. Each 10% delay in SGA initiation post-discharge was associated with a 2, 1, and 6% higher risk for polypharmacy (95% CI: 1.01-1.02), gap (95% CI: 1.01-1.01), and clozapine (95% CI: 1.04-1.08), respectively.InterpretationSchizophrenia patients accumulated more time unmedicated and in polypharmacy compared to clozapine. Either treatment guidelines for schizophrenia are not followed, or real-world challenges hamper their implementation.
| S-EPMC9243750 | biostudies-literature