The management of antipsychotic-induced weight gain
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Date
2025
Authors
Fitzgerald, Ita
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
Introduction
Those living with a severe mental illness (SMI) have a life expectancy estimated as 15-20 years shorter than the general population, with those living with schizophrenia being the most adversely affected. Approximately 40-50% of this excess mortality has been estimated as attributable to death secondary to premature cardiovascular disease (CVD). High rates of obesity are a recognised significant contributor to the burden of CVD among SMI cohorts. Whilst antipsychotic medications are essential treatments in psychiatry, the prescription of any antipsychotic substantially increases the risk of developing obesity. Thus, effective management of antipsychotic-induced weight gain (AIWG) is paramount in addressing the burden of premature mortality among people living with a SMI.
Despite its prevalence and impact, international AIWG management practices continue to be suboptimal. This is in part due to deficits in the design of clinical practice guidelines addressing AIWG management. This includes the absence of recommendations considering prevention or early intervention and the absence of lived experience informing recommendation development. Precluding the development of evidence-based, patient-centred AIWG management guidelines are also significant gaps within available research. This includes: (i) whether those at highest risk of clinically significant AIWG can be identified prior to, or early in, treatment to facilitate early intervention, (ii) how application of shared decision-making (SDM) within antipsychotic prescribing can be increased to address the problem of excessive prescribing of antipsychotics associated with a high-risk of inducing AIWG, and (iii) how those with lived experience of AIWG conceptualise preferred management to ensure recommendations are acceptable, feasible, and transferable across cohorts.
The overarching aim of this thesis was to provide answers to these research questions. Thesis objectives were:
i. To ascertain whether routinely collected non-genetic prognostic factors can predict weight outcomes following antipsychotic initiation.
ii. To generate an in-depth understanding of how to implement SDM within antipsychotic prescribing decisions within psychosis management.
iii. To elicit the values and preferences of people with experience of AIWG regarding patient-centred AIWG management.
Methods
A systematic review and meta-analysis was undertaken to identify, synthesize, and appraise research evaluating non-genetic prognostic factors and their association with anthropometric outcomes following antipsychotic initiation. Subsequently, a realist review was undertaken addressing – from the perspective of prescribers – how interventions designed to improve SDM application within antipsychotic prescribing decision work and elicit the impact of structural and contextual factors on their successful implementation within real-world settings. Finally, a qualitative descriptive study was completed exploring the management experiences of varying individuals with experience of unwanted AIWG, alongside eliciting their values and preferences for preferred management.
Results
Systematic review results assessed seventy-eight prognostic factors across 29 studies (4,706 participants) and identified trend of early body mass index (BMI) increase as the most clinically significant prognostic factor influencing long-term AIWG prognosis. Previously thought prognostic factors were identified as non-significant following synthesis of primary research. This included age (b=-0.044, 95%CI -0.157-0.069), sex (b=0.236, 95%CI -0.086-0.558), and baseline BMI (b=-0.013 95%CI -0.225-0.200).
From the realist review, ten programme theories containing 23 context-mechanism-outcome configurations (CMOCs) were developed from 106 data sources. Programme theories 1-5 addressed implementing SDM within psychosis management and the impact of policy, governance, and system factors. These five programme theories outlined relationships between (i) leadership and governance, (ii) workforce development and (iii) service delivery contexts and their impact on reducing prescriber engagement with behaviours required of SDM application. Key mechanisms reducing prescriber engagement in desired behaviours included: (i) a fear of individual blame for adverse outcomes and exposure to liability, (ii) pressure from service environments to prioritise decreasing risk of harm, (iii) inadvertent devaluing of experiential knowledge and (iv) existing beliefs that SDM conflicts with duties of beneficence and non-maleficence. Within programme theories 6-10, facilitative features within service delivery and workforce development contexts that can increase prescriber engagement with behaviours required of SDM were outlined. Key mechanisms included: (i) reducing prescriber fear of sole responsibility for harm, (ii) reducing the perceived burden of SDM within consultations, (iii) increasing prescriber confidence in their ability to productively negotiate treatment consultations and (iv) increasing prescriber confidence to safely increase patient autonomy within decision-making.
Finally, semi-structured qualitative interviews (n=17) highlighted significant changes required in current AIWG management guidance for such guidance to reflect the values and preferences of those with lived experience. Participants reported current guidance is oversimplified, lacks the specificity and scope required, and endorses a ‘one-size-fits-all’ management approach to an extensively heterogenous side-effect. Patient-centred AIWG management was outlined as collaborative, where guidance prioritises early intervention using the range of management interventions, tailored according to AIWG risk, participant ability, and participant preference.
Conclusion
This thesis addressed several key, previously unaddressed research questions within AIWG management, and thus, has significantly advanced knowledge in patient-centred, evidence-based AIWG management. The systematic review provided the first mapping and statistical synthesis of studies examining non-genetic prognostic factors within AIWG prognostication and produced practice, policy, and research implications. This included application of early BMI trend change to target use of intensified management interventions to those at highest risk of the poorest long-term anthropometric outcomes. The realist review identified that, despite significant research in optimising the design of interventions for use within antipsychotic treatment consultations, e.g., decision aids, even empirically efficacious interventions will be difficult to implement at scale within real-world settings due to misalignment of the behaviours required of clinicians to engage in SDM with the complex social, cultural, legal, political, and professional realities common to mental health settings. Mechanisms identified as responsible for increasing or decreasing prescriber engagement with behaviours required for effective SDM application, and the contexts responsible for their activation, should be the focus of those responsible for implementing SDM at organisational and institutional level. Use of qualitative research results within future iterations of AIWG management guidelines will ensure recommendations are relevant and applicable, and thus, providing opportunities to maximise the impact of recommendations in practice for those funding, providing, and using services.
Description
Keywords
Antipsychotic , Weight gain , Psychosis , Pharmacological management
Citation
Fitzgerald, I. 2025. The management of antipsychotic-induced weight gain. PhD Thesis, University College Cork.