Estimating and Interpreting Effects from Nonlinear Exposure-Response Curves in Occupational Cohorts Using Truncated Power Basis Expansions and Penalized Splines

Truncated power basis expansions and penalized spline methods are demonstrated for estimating nonlinear exposure-response relationships in the Cox proportional hazards model. R code is provided for fitting models to get point and interval estimates. The method is illustrated using a simulated data set under a known exposure-response relationship and in a data application examining risk of carpal tunnel syndrome in an occupational cohort

Polypharmacy and Antidepressant Acceptability in Comorbid Depression and Type 2 Diabetes

BACKGROUND: Polypharmacy may increase the risk of drug interactions, side-effects and poor adherence. However, the impact of polypharmacy on antidepressant acceptability in individuals with type 2 diabetes (T2DM) is unknown. AIM: In adults with T2DM, to investigate the association between the number of prescribed medications and: i) early antidepressant discontinuation (<32 weeks); ii) switching antidepressant agents. DESIGN: Cohort study using UK primary care data from the years 2000-2018. METHODS: We used cox regression with penalised B-splines to describe the association between the number of concurrently prescribed medications at the time of starting antidepressant treatment, and each of our outcomes. RESULTS: We identified 73,808 individuals with comorbid depression and T2DM starting antidepressant treatment for the first time. The median number of concurrent medications prescribed was 7. Within 32 weeks, 44.26% of participants discontinued antidepressant treatment altogether, and 11.75% of participants switched antidepressant agents. We found an inverse relationship between the number of concurrent medications and discontinuing antidepressant treatment altogether. The median number of 7 concurrent medications was associated with a 65.06% decrease early antidepressant discontinuation HR 0.45, 95% CIs 0.37-0.55). We found no evidence of an association, in our main analysis, between the number of concurrent medications and switching antidepressant agents. CONCLUSIONS: Early discontinuation of antidepressants is common in adults with T2DM. However, individuals with higher levels of concurrent polypharmacy may be more adherent to treatment. These are likely to represent individuals with worse physical/mental health. Individuals with lower levels of concurrent polypharmacy may benefit from adherence support