Mortality risk from long-term treatment with antipsychotic polypharmacy vs monotherapy among adults with serious mental illness: A systematic review and meta-analysis of observational studies

Buhagiar, Kurt; Templeton, Georgia; Blyth, Henrietta; Dey, Mrinalini; Giacco, Domenico

doi:10.1016/j.schres.2020.08.026

Cited by 9 publications

(14 citation statements)

References 44 publications

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“…Psychotropic polypharmacy, particularly during the treatment of elderly people with SMI, seems to be associated with greater adverse effects on most physical diseases, compared to monotherapy ( 4 ), as it carries the risk of adverse drug reactions. As the possible contribution of antipsychotic polypharmacy to the general excess mortality in people with SMI remains unclear ( 110 , 111 ), further meta-analyses are needed analyzing mortality outcomes based on specific antipsychotic combinations rather than pooling data irrespective ( 111 ). The risks of adverse drug reactions due to psychotropic polypharmacy may be higher among certain regions in the world.…”

Section: Discussionmentioning

confidence: 99%

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

et al. 2022

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Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings.Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics.Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.

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Section: Discussionmentioning

confidence: 99%

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

et al. 2022

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“…Our findings are broadly consistent with previous literature, although we note that prior attempts to systematically synthesize findings across heterogeneous studies investigating the safety of APP have sometimes been inconclusive (Gallego et al ., 2012; Fleischhacker and Uchida, 2014; Takeuchi et al ., 2015; Kadra et al ., 2018b, 2018a; Patel et al ., 2018; Taipale et al ., 2018; Buhagiar et al ., 2020). Further research utilising comparable datasets would strengthen the evidence to inform the use of APP in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic Polypharmacy and Adverse Drug Reactions Among Adults in a London Mental Health Service, 2008-2018

Yang

Thygesen

Werbeloff

et al. 2021

Preprint

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BackgroundAntipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions. Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2+ antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of adverse drug reactions: QT interval prolongation, hyperprolactinaemia, and increased body weight (body mass index [BMI] ≥ 25).MethodsWe extracted anonymised EHR data. Patients aged 16+ receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.ResultsWe identified 35,409 observations of antipsychotic prescribing among 13,391 patients. APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% C.I. 1.87-3.24) and of having a BMI > 25 (adjusted odds ratio 1.75; 95% C.I. 1.33-2.31) in the period following the APP prescribing.ConclusionsOur observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

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“…Conversely, therapeutically useful effects on AE outcome may be achieved by partial DA agonist add-on to CLZ, RIS, OLA, or HAL, to relieve metabolic- and prolactin (PRL)-derived issues ( vide infra ). Although so far available data are insufficient to allow definitive conclusions it would appear that—contrary to what may be widely presumed—there is a priori no general tolerability, AE, or safety [including mortality; e.g., ( 20 , 21 )] reason to discard APP as a possible strategy for a patient in need thereof.…”

Section: App: Why When and To Whom?mentioning

confidence: 90%

The More, the Merrier…? Antipsychotic Polypharmacy Treatment Strategies in Schizophrenia From a Pharmacology Perspective

Stephan

2021

Front. Psychiatry

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Antipsychotic polypharmacy/drug combination treatment (APP) is a remarkably common practice in the schizophrenia context, given the lack of general support in treatment Guidelines. There is also a vast literature on APP outcomes, but a paucity of high-quality evidence-based data to guide and optimize adequate use of APP. This seems particularly true regarding many pharmacology-based considerations involved in APP treatment strategies. This paper first briefly summarizes clinical literature related to the use of APP. Against this backdrop, the pharmacological target profile features are then described of frequently used antipsychotic agents, in relation to estimated free plasma exposure levels at clinically efficacious dosing. APP strategies based on the properties of these drugs are then scrutinized and gauged within the background literature framework. The anticipated usefulness of APP from the pharmacological standpoint is detailed regarding efficacy, adverse effect (AE)/tolerability, and safety perspective, including why, when, and how it may be used to its advantage. For the purpose, a number of theoretically beneficial combinations as well as instances with suboptimal—and even futile—APP approaches are exemplified and discussed from the rational pharmacodynamic and pharmacokinetic pros and cons point-of-view. In this exposé, particular attention is paid to the utility and features of 3rd Generation Antipsychotic dopamine (DA) D2-D3 agonists within an APP setting.

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Mortality risk from long-term treatment with antipsychotic polypharmacy vs monotherapy among adults with serious mental illness: A systematic review and meta-analysis of observational studies

Abstract: Please refer to published version for the most recent bibliographic citation information. If a published version is known of, the repository item page linked to above, will contain details on accessing it.

Cited by 9 publications

References 44 publications

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

Antipsychotic Polypharmacy and Adverse Drug Reactions Among Adults in a London Mental Health Service, 2008-2018

The More, the Merrier…? Antipsychotic Polypharmacy Treatment Strategies in Schizophrenia From a Pharmacology Perspective

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