Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia

ABSTRACT

Introduction: Patients living with schizophrenia have a marked risk of clinically significant weight gain and obesity compared to the general population. The risks have been highlighted following the introduction of second-generation antipsychotics. In turn, obesity is associated with a higher prevalence of cardiovascular disease, the most common cause of premature mortality in patients with schizophrenia.

Areas covered: In this review, the authors outline possible mechanisms that induce obesity in patients with schizophrenia taking antipsychotics. The authors discuss the safety and effectiveness of three main approaches for attenuating antipsychotic-associated weight gain (AAWG), including lifestyle interventions, switching antipsychotics, and augmentation with other medications.

Expert opinion: When selecting antipsychotics, effective treatment of psychotic symptoms should be highest priority but obesity and related metabolic comorbidities associated with antipsychotics should not be neglected. Further research into mechanisms of weight gain associated with antipsychotics will guide future treatments for AAWG and development of antipsychotics that produce minimal metabolic adverse effects. With current strategies only producing modest weight loss in already overweight and obese individuals, clinicians should transition to an approach where they aim to prevent weight gain when initiating antipsychotic treatment.

KEYWORDS:

• Antipsychotic
• lifestyle
• mechanisms
• obesity
• pharmacological
• schizophrenia
• weight gain
• switching

Article highlights

• The introduction of second-generation antipsychotics has resulted in higher incidences of metabolic risk factors, specifically obesity.

• The mechanisms responsible for antipsychotic-induced weight gain are believed to be changes in hormones and peptides involved in energy homeostasis, antagonism of receptors in appetite and satiety centers, and pharmacogenetic differences between patients. Additionally, recent research has demonstrated a possible role of the gut microbiome.

• Lifestyle interventions including exercise, nutritional advice, and cognitive-behavioral therapy have shown modest reductions in weight gain. However, to be effective such interventions must be adequately designed and resourced in order to promote adherence and lifestyle changes in this population.

• Switching to antipsychotics with a lower risk of inducing weight gain such as aripiprazole, ziprasidone, and amisulpride may show promise but applicability is limited by poorly designed studies with high discontinuation rates (largely due to symptom exacerbation).

• Augmentation with other medications is an effective strategy. Metformin and GLP-1RAs have the most robust data demonstrating favorable reductions in weight and minimal reports of serious side effects.

This box summarizes key points contained in the article.

Declaration of interest

DS is supported in part by an NHMRC APP1111136. D Siskind is supported in part by an NHMRC ECF APP1111136. BH Ebdrup has received lecture fees and/or is part of Advisory Boards of Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia AB, Takeda Pharmaceutical Company and Lundbeck Pharma A/S. MK Hahn has been on an advisory board for Alkermes. S Kisely has received speaker’s honoraria from Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received consulting honoraria from Alkermes, Indivior, Pear Therapeutics, and Alto. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.