This study has revealed that people who suffer from severe mental disorders like schizophrenia and bipolar affective disorder do not compare favorably with the rest of the population regarding lifespan. The major risk factors attributed include those highly cardiometabolic in nature. Being overweight and obese highly contributes to these cardiometabolic risks since obesity causes mortality, and creates coronary heart disease, stroke, and type 2 diabetes mellitus (T2DM). Approximately three-quarters of those who suffer psychosis have co-morbid overweight or obesity.
The weight trajectory is rapid and nonlinear in people with SMI, for instance, within a year of starting treatment almost 80% of first-episode psychosis patients will experience clinically significant weight gain (defined as any increase in baseline body weight by equal to or greater than 7%). A UK longitudinal study showed that in the 5 years following the first prescription of an antipsychotic, over 50% of individuals within the healthy weight category at baseline progressed to overweight/obesity.
Weight gain and obesity are very common among patients suffering from severe mental illness (SMI). Its management by pharmacotherapy has the most common and distressing side effect being antipsychotic-induced weight gain (AIWG), and people living with SMI value that it is avoided. Metformin is the best investigative pharmacological preventive measure for AIWG, but guidelines are not clear and there is no translation into practice from the evidence. The study sought to develop a guideline on the use of metformin in the prevention of AIWG.
Metformin is the only truly efficacious pharmacological agent for the prevention of AIWG. Concomitant initiation with the antipsychotic drugs seems to reduce the enhancement of weight gain by 4.03 kg (95% CI -5.78 kg to -2.28 kg) from controls. The treatment consensus guideline for the use of metformin for preventing AIWG has published specific recommendations concerning degrees of concomitant initiation with metformin at the time of initiation with an antipsychotic or initiation if any of several criteria are met. Important recommendations were classified as strong by consensus agreement.
There are limitations by nature in developing and implementing guidelines. Thus, no matter how high on evidence, a recommendation for or against an intervention would still call for subjective judgment among a panel weighing possible benefits against possible harms. The recommendations will, of necessity, carry values, which may therefore be different from the value systems of the service user or the clinicians applying the guideline into practice. It was developed according to the evidence-based framework AGREE II, which incorporates consensus validation and independent external reviews and the values of service users through PPI partners from concept development.
Metformin is the only drug that is proven to prevent AIWG. Co-issued together with the antipsychotic medications, they will lessen the weight gain relative to controls, and some evidence suggests larger effect sizes for longer durations of use for these high-risk antipsychotic medicines. We describe robust methods for guideline development of using metformin for the prevention of AIWG with an allowance for co-initiation with an antipsychotic or initiation if certain criteria are met with that metformin.
Among pharmacological agents, metformin was the sole one that has shown effectiveness in preventing AIWG; this study describes how a clinical practice guideline for this indication was developed by following an evidence-based framework employing robust and transparent methods. The algorithm will have core recommendations on the co-initiation of metformin with an antipsychotic or when certain criteria are met. Important prescribing information as good practice recommendations have also been incorporated for implementation purposes.
The implementation and evaluation of the guideline will be made possible using a shared decision-making package and barrier/facilitator assessment. This research describes how an evidence-based framework used robust and transparent methods to develop a clinical practice guideline for this indication because metformin is, so far, the only drug proven effective in preventing AIWG.
Reference: Carolan A, Hynes-Ryan C, Agarwal SM, et al. Metformin for the prevention of antipsychotic-induced weight gain: guideline development and consensus validation. Schizophr Bull. 2024; sbae205, https://doi.org/10.1093/schbul/sbae205
