The Effect of Semaglutide With Lifestyle Intervention on the Physical Health of Patients Treated With Antipsychotic Drugs in a Secure Mental Health Setting: Protocol for an Uncontrolled Pretest-Posttest Pilot Mixed Methods Study.

Background: Antipsychotic-induced weight gain is a common side effect of antipsychotic drug treatment, particularly with second-generation medications such as clozapine and olanzapine. Weight gain in patients undergoing antipsychotic therapies is a significant concern, often compounded by factors related to their condition that can be particularly challenging in a secure care setting. While there is significant evidence to support the benefits of semaglutide, one of the available glucagon-like peptide-1 receptor agonists, in promoting weight loss for those who have a general weight-related health issue and meet the referral criteria for specialist services, it is unclear whether it will be as successful in people who have specifically gained weight due to medication-associated side effects and who reside in a secure care setting. Objective: This study aims to assess the impact of semaglutide in combination with a lifestyle behavior change intervention on the physical health measures of patients in a secure setting who have atypical antipsychotic-induced weight gain and identify enhancements to the intervention, specifically geared toward improving adherence and acceptability from both staff and patient perspectives. Methods: This 2-year uncontrolled pretest-posttest pilot study aims to recruit 20 inpatient participants. Adult patients of any diabetic status with a minimum BMI of 35.0 kg/m2 (or a BMI of 32.5 kg/m2 for people from South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean descent) who are receiving inpatient treatment and are treated with either olanzapine or clozapine will be eligible for inclusion in the study. Patients will receive semaglutide (Wegovy) at a maintenance dose of 2.4 mg once a week for 2 years. All participants will also receive a lifestyle behavior change intervention. Results: The findings will reveal whether the format of the interventional approach is both sustainable and effective for adult patients diagnosed with severe mental illness and living with obesity who are currently residing in a secure mental health setting. Implementation changes that could improve the acceptability of and adherence to the intervention will be explored. Conclusions: This research should be beneficial for patients with severe mental illness who are living with obesity and are residing in a secure setting as the findings may ultimately reduce the mortality risk in this patient group.