This randomized, rater-blind, multicenter clinical trial will evaluate whether a personalized pharmaco-lifestyle intervention improves mental functioning in adults with severe mental illness, including schizophrenia, bipolar disorder, or major depressive disorder. Participants will be randomized to either a modular individualized intervention program or a structured psychoeducation control condition. The individualized intervention may include physical exercise, an anti-inflammatory diet, sleep intervention, social prescribing, semaglutide for eligible participants with overweight or obesity, and optional closed-loop transcranial alternating current stimulation for participants with prominent depressive symptoms. The primary outcome is change in the SF-36 Mental Component Summary score from baseline to Month 3.
Age 18 to 65 years
Able and willing to provide written informed consent
Diagnosis of schizophrenia, bipolar disorder, or major depressive disorder according to DSM-5-TR, confirmed by M.I.N.I.
Female participants of childbearing potential must agree to use an effective method of contraception
Unable to provide informed consent
Current or past neurological disorder or structural brain pathology that may affect study procedures
Known intolerance or hypersensitivity to semaglutide
Pregnancy or lactation