Predictors of benefits and safety events from participation in a lifestyle therapy trial for adults with depression: A secondary analysis of the CALM randomised controlled trial

OBJECTIVE: Lifestyle-based interventions are increasingly popular for treating depression, yet a comprehensive evaluation of who benefits or may be harmed is limited. This study examined predictors of benefits and safety events, and the types of these events experienced by participants in the CALM trial, which compared lifestyle therapy with psychotherapy for depression. METHODS: 'Benefit' was defined as a ⩾ 50% reduction in Patient Health Questionnaire-9 scores, along with self-reported or staff-observed safety events. Generalised estimating equations identified predictors of benefit and safety events, reporting risk ratios and beta coefficients. Exploratory subgroup analyses were conducted by treatment arm (lifestyle vs psychotherapy). RESULTS: Of 132 completers, 38% met criteria for benefit and 78% reported at least one safety event. Older age (RR = 1.14, 95% CI [1.01, 1.30]) and being born overseas (RR = 1.59, 95% CI [1.06, 2.38]) predicted benefit. Older age (β = 0.16, 95% CI [0.05, 0.26]) and higher baseline glucose (β = 0.16, 95% CI [0.10, 0.23]) were associated with more safety events. Subgroup analyses indicated that age predicted benefit in the psychotherapy arm, while place of birth predicted benefit in the lifestyle arm. Safety events were more common in the lifestyle arm among participants who were older or had elevated glucose. CONCLUSION: In the CALM trial, older age and being born overseas predicted benefit, while older age and higher glucose levels were associated with greater safety events. These findings provide clinicians and consumers with a clearer risk-benefit profile of behavioural therapies and support personalised treatment based on consumer characteristics. REGISTRATION: Australian and New Zealand Clinical Trials Registry (https://www.anzctr.org.au/; ACTRN12621000387820).