Adherence to a Mediterranean diet and leisure-time physical activity are protective factors against the initiation of antidepressant, anxiolytic, antipsychotic, and antiseizure drug use in older adults: a cohort study

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ABSTRACT Background We aimed to investigate the association between long-term adherence to MedDiet and LTPA levels and the initiation of antidepressant, anxiolytic, antipsychotic and antiseizure medication in older adults. Methods. We assessed the relationship between the cumulative average of MedDiet adherence and LTPA and the initiation of medications in the PREvención con DIeta MEDiterránea (PREDIMED) study. Sample sizes ranged from 5,940 for anxiolytics to 6,896 for antipsychotics. Associations between the cumulative average of MedDiet adherence (per each one-point increase in the adherence score) and LTPA (per each increase in 20 metabolic equivalents of task-minute/day [METs-min/day]) with drug initiation were studied by multivariable Cox regressions (covariates: age, sex, PREDIMED intervention group, recruitment site, education, smoking habit, BMI, alcohol, and energy intake; multiple comparisons: Bonferroni method). We explored non-linear exposure-outcome associations using smoothed cubic splines and the interaction among both exposures. Results One-point increases in MedDiet adherence score were associated with 23-28% less initiation of antidepressants (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77), anxiolytics (HR 0.75, 95%CI 0.70-0.81), antipsychotics (HR 0.77, 95%CI 0.65-0.91), and antiseizure drugs (HR 0.77, 95%CI 0.69-0.85). Associations for anxiolytics and antiseizure drugs were particularly strong among participants with poor MedDiet adherence. Relationships between LTPA and initiation of antidepressant and anxiolytic drug use were non-linear. Among participants with the lowest LTPA values (0-150 METs-min/day), 20 METs-min/day increases were associated with 20% less risk of initiating antidepressant use (HR 0.80, 95%CI 0.75-0.86) and 15% less risk of initiating anxiolytic medication (HR 0.85, 95%CI 0.79-0.90). 20 METs-min/day increases were linearly associated with less initiation of antiseizure drugs (HR 0.96, 95%CI 0.94-0.99), and no clear associations were found for antipsychotic drugs. Individuals with high MedDiet adherence (≥10 adherence points) and high LTPA levels (≥150 METs-min/day) showed 42-59% less risk of initiating psychoactive drugs (antidepressants: HR 0.41, 95%CI 0.30-0.56; anxiolytics: HR 0.54, 95%CI 0.41-0.71; antipsychotics: HR 0.45, 95%CI 0.21-0.95; antiseizure drugs: HR 0.58, 95%CI 0.37-0.90). The combination was additive for antidepressants, antipsychotics and antiseizure drugs and synergistic for anxiolytics ( p -interaction = 0.076). Conclusions Sustained adherence to MedDiet and LTPA were linked to lower initiation of psychoactive drugs in older adults.

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