Patients with severe mental illness (SMI) have a 1.4- to 2-fold increased risk of obesity, diabetes and cardiovascular disease as compared to the general population1. Antipsychotic medications have been a cornerstone of treatment for SMI, particularly schizophrenia and bipolar disorder, for several decades. Antipsychotics can reduce symptoms, prevent relapses, stabilize mood, and enable people with SMI to better function in their day-to-day lives. While antipsychotics offer significant benefits in managing psychiatric disorders, it is essential to recognize that like any medication, antipsychotics can also be associated with adverse events1,2. Side effects of antipsychotics can impair health-related quality of life, contribute to morbidity/mortality, increase stigma, decrease adherence to prescribed treatment regimens and thus increase the risk of relapse1,2,6,10. At SIRS 2023, a panel of researchers convened to discuss how to optimally manage antipsychotic adverse effects.
Patients with severe mental illness have a 1.4- to 2-fold increased risk of obesity, diabetes and cardiovascular disease compared to the general population.
Antipsychotic-associated weight gain
People with schizophrenia are two times more likely than the general population to be overweight3. Prof. Margaret Hahn (Center for Addiction and Mental Health, Canada) shared the findings of her team’s Cochrane review of Schizophrenia's Register of Trials that examined adjunctive pharmacological interventions for weight gain prevention in patients with SMI who use antipsychotic medications3,4. A common first line antihyperglycemic medication (biguanide) was effective at promoting modest weight loss4, and is currently recommended in the Canada Adult Obesity clinical practice guidelines4,5. Prof. Hahn added that glucagon-like peptide-1 receptor antagonists (GLP-1 Ras) have accumulating evidence supporting their efficacy at weight reduction in patients with schizophrenia taking antipsychotic medication4; however, their use is not yet recommended in guidelines4.
People with schizophrenia are two times more likely than the general population to be overweight.
Switching antipsychotics
Prof. Dan Siskind (Metro South Addiction and Mental Health Service, Australia) explained that antipsychotic medications can lead to weight gain due to glucose dysregulation and increased appetite. While addition of pharmacological agents intended to prevent weight gain may help, he and his team also aimed to explore the impact of switching antipsychotic agents6.
The team conducted a systematic review and meta-analysis of 59 studies which reported weight and metabolic changes following switching of antipsychotic agents7. They found that switching antipsychotic agents to one with lower weight gain potential can have a favourable outcome with respect to weight gain and cardiometabolic outcomes7. In particular, a common second generation atypical antipsychotic and a third generation atypical antipsychotic improved weight and cardiometabolic profiles6,7.
Prof. Siskind cautioned that considering an antipsychotic switch involves balancing the pros and cons of a favourable change in weight versus the risk of a flare in psychiatric symptoms7.
Switching antipsychotic agents to one with lower weight gain potential can have a favourable outcome with respect to weight gain and cardiometabolic outcomes.
Sex influences on antipsychotic side effects
Bodyl Brand (PhD candidate, University of Groningen, Netherlands) spoke about the differential course of illness and treatment response between male and female patients with schizophrenia8. Because women absorb, metabolize and eliminate drugs more slowly than men, they are more likely to experience overdoses and side effects.
Because women absorb, metabolize and eliminate drugs more slowly than men, they are more likely to experience overdoses and adverse effects.
The pharmacokinetic (PK) handling of drugs differs between men and women; specifically, gastric emptying, gastrointestinal transit time, and renal elimination are all slower in women than in men8,9. Due to these PK differences, women often experience more severe adverse effects than men, and are at risk of overdose since current treatment guidelines do not consider sex differences8,9.
Estrogen seems to have a protective effect in the context of psychiatric disorders; premenopausal women often have a better course of illness than men9, and when estrogen levels decline in the menopausal years, antipsychotic effectiveness seems to decline and the risk of relapse seems to increase8. Starting at age 45–50, women are more frequently hospitalized for psychotic episodes than men8.
Sex-specific dosing guidelines are needed to prevent overdoses in women.
Due to these sex differences on antipsychotic efficacy and adverse effects, Ms. Brand concluded that clinicians need to be aware of the increased risks of overdosing and increased burden of adverse effects in women, and consider sex-specific dosing guidelines8,9.
Digital tools in choosing antipsychotics
Prof. Rob McCutcheon (University of Oxford, UK) presented a novel digital tool designed to assist clinicians as they choose between different anti-psychotics.
He explained that one factor contributing to variability of adverse effects incidence is the affinity of different agents for their receptors. Clustering antipsychotics based on receptor affinity reveals four groups of antipsychotics: muscarinic receptor antagonists, adrenergic antagonists/dopamine partial agonists, serotonergic and dopaminergic antagonists, and pure dopaminergic antagonists. This grouping scheme both reflects pharmacological profiles and predicts adverse effects10.
The novel digital tool is a data-driven approach which combines the classification of antipsychotics based on receptor affinities, and the results of an umbrella review of 13 different adverse effects of 32 different antipsychotics10. It can assist clinicians to provide evidence-based, personalized treatment options based on the level of concern for one adverse effect over another10.
Conclusions
Collectively, the speakers reviewed evidence-based approaches which can help clinicians to meet the recommendations of recently published guidelines which urge the safeguarding of the physical health of patients with SMI1,2.
Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
