Therapeutic adherence promotion program for severe mental illness: the ADHERA study protocol

Background

Treatment adherence is one of the most relevant determinants of clinical outcomes in severe mental illnesses (SMI), particularly schizophrenia and bipolar disorder. Insufficient adherence to antipsychotic medication is consistently associated with higher relapse rates, increased hospital admissions, poorer functional outcomes, reduced quality of life, and a substantial economic burden on healthcare systems (1). Despite its clinical relevance, adherence remains difficult to measure accurately. For decades, self-report questionnaires have been the most widely used tools in routine clinical practice and research settings. However, these measures are vulnerable to recall bias, social desirability, limited insight, and their inherently cross-sectional nature. The progressive implementation of electronic prescription and dispensing systems offers a unique opportunity to assess adherence objectively and longitudinally, using real-world data derived from patients’ medication collection patterns (2).

Objectives

The ADHERA study has three primary objectives: 1. to evaluate the concurrent validity of digital self-reported adherence questionnaires by comparing them with objective antipsychotic dispensing data obtained from the Single Prescription Module (Módulo Único de Prescripción, MUP), considered the gold standard; 2. to identify sociodemographic and clinical factors associated with poor adherence in patients with schizophrenia and bipolar disorder; and 3. to assess the effectiveness and feasibility of a telematic psychoeducational intervention aimed at improving adherence in patients identified as non-adherent.

Methods

This multicenter study will be conducted in the Psychiatry Departments of four general hospitals in the Community of Madrid. The protocol integrates three complementary methodological approaches within a single cohort: a validation study of adherence measures, an observational analysis of adherence-related factors, and a pre–post intervention study. Eligible participants include adults (≥18 years) diagnosed with schizophrenia and/or bipolar disorder according to ICD-11 criteria, registered on the Patient Portal, and with an active antipsychotic prescription recorded in the MUP. Objective adherence will be calculated as the percentage of medication exposure over the preceding six months based on dispensing records. Subjective adherence will be assessed using the Morisky–Green 7-item scale and the Haynes–Sackett question. Diagnostic accuracy indicators (sensitivity, specificity, predictive values) and ROC curve analyses will be performed to validate self-report instruments. Multivariate regression and correlation analyses will be used to explore factors associated with non-adherence.

Patients identified with poor adherence will be invited to participate in a structured telehealth psychoeducational intervention consisting of ten group sessions delivered via videoconference by clinical psychologists. The intervention includes peer-support elements, with testimonials from stabilized patients, in order to promote a non-coercive and patient-centered approach. Adherence will be reassessed six months after the intervention using both objective dispensing data and self-report measures.

Expected Results and Conclusions: Approximately 50% of the target population is expected to exhibit suboptimal adherence at baseline. The intervention is hypothesized to produce a clinically meaningful improvement in medication exposure and self-reported adherence scores. By combining digital health data with telematic psychosocial strategies, this study proposes an innovative and scalable model for optimizing treatment adherence and improving long-term outcomes in severe mental illness.

References

1. Loots E, Goossens E, Vanwesemael T, Morrens M, Van Rompaey B, Dilles T. Interventions to Improve Medication Adherence in Patients with Schizophrenia or Bipolar Disorders: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2021 Sep 28;18(19):10213. doi: 10.3390/ijerph181910213. PMID: 34639510; PMCID: PMC8508496. 2. Roden DM, Xu H, Denny JC, Wilke RA. Electronic medical records as a tool in clinical pharmacology: opportunities and challenges. Clin Pharmacol Ther. 2012 Jun;91(6):1083-86. doi: 10.1038/clpt.2012.42. PMID: 22534870; PMCID: PMC3819803.