PT - JOURNAL ARTICLE AU - Ryan Smith AU - Sahib Khalsa AU - Martin Paulus TI - An Active Inference Approach to Dissecting Reasons for Non-Adherence to Antidepressants AID - 10.1101/743542 DP - 2019 Jan 01 TA - bioRxiv PG - 743542 4099 - http://biorxiv.org/content/early/2019/11/29/743542.short 4100 - http://biorxiv.org/content/early/2019/11/29/743542.full AB - Background Antidepressant medication adherence is among the most important problems in health care worldwide. Interventions designed to increase adherence have largely failed, pointing towards a critical need to better understand the underlying decision-making processes that contribute to adherence. A computational decision-making model that integrates empirical data with a fundamental action selection principle could be pragmatically useful in 1) making individual level predictions about adherence, and 2) providing an explanatory framework that improves our understanding of non-adherence.Methods Here we formulate a partially observable Markov decision process model based on the active inference framework that can simulate several processes that plausibly influence adherence decisions.Results Using model simulations of the day-to-day decisions to take a prescribed selective serotonin reuptake inhibitor (SSRI), we show that several distinct parameters in the model can influence adherence decisions in predictable ways. These parameters include differences in policy depth (i.e., how far into the future one considers when deciding), decision uncertainty, beliefs about the predictability (stochasticity) of symptoms, beliefs about the magnitude and time course of symptom reductions and side effects, and the strength of medication-taking habits that one has acquired.Conclusions Clarifying these influential factors will be an important first step toward empirically determining which are contributing to non-adherence to antidepressants in individual patients. The model can also be seamlessly extended to simulate adherence to other medications (by incorporating the known symptom reduction and side effect trajectories of those medications), with the potential promise of identifying which medications may be best suited for different patients.