Medication Adherence in Severe Mental Illness: a Promotion Program (ADHERA)

February 25, 2026 updated by: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Therapeutic Adherence Promotion Program for Severe Mental Illness: the ADHERA Study Protocol

People living with serious mental illnesses such as schizophrenia and bipolar disorder often need long-term medication to stay well. However, many patients have difficulty taking medication regularly, which can increase the risk of relapse, hospitalization, and poorer quality of life. Traditionally, treatment adherence has been measured using self-report questionnaires, which may be influenced by memory or social desirability bias.

With the recent expansion of electronic prescription systems in Spain, it is now possible to objectively verify whether patients collect their medications from the pharmacy. This provides a new opportunity to better understand and support treatment adherence.

The ADHERA study will evaluate how well digital self-report questionnaires reflect real medication use compared with electronic dispensing records. We will also explore patient characteristics that may be associated with difficulties in medication adherence. Finally, we will test a new online psychoeducational program-including sessions led by mental health professionals and supported by peer-experience contributors-to determine whether it can help improve adherence.

Participants with schizophrenia or bipolar disorder who are registered in the hospital's digital patient portal and have active antipsychotic prescriptions will be invited to complete brief adherence questionnaires online. Individuals with signs of reduced adherence will then be invited to take part in a telehealth intervention consisting of ten group sessions, where they will receive information, support, and practical strategies to maintain their treatment plan. Medication adherence will be reassessed after six months.

If successful, this study may help improve how treatment adherence is measured in clinical practice, guide targeted interventions for individuals at higher risk of non-adherence, and provide evidence for scalable telehealth programs that can be easily implemented in other regions and medical conditions

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study aims to evaluate the validity of digital self-reported treatment adherence questionnaires in comparison with objective pharmacy dispensing records for antipsychotic medications, identify predictors of non-adherence, and assess the effectiveness of a telehealth intervention designed to improve adherence among adults with schizophrenia or bipolar disorder.

Study Design

The protocol incorporates three linked components:

Validation study: Sensitivity, specificity, predictive values, and ROC analysis will be used to determine the accuracy of digital adherence self-report scales compared with electronic dispensing data from the regional Single Prescription Module (MUP), considered the reference standard.

Observational study: Sociodemographic and clinical variables obtained through the Patient Portal will be analyzed to identify correlates of adherence. Logistic regression and correlation models will be applied to examine associations between treatment exposure (continuous and categorical measures) and relevant predictors.

Pre-post intervention: Participants identified as having poor adherence will be offered a structured psychoeducational program delivered via videoconference. The program includes ten group sessions led by clinical psychologists and two peer-contributor sessions, focusing on knowledge reinforcement, self-management skills, and barriers to adherence. Medication exposure levels and self-report scores will be reassessed six months post-intervention.

Setting and Population Participants will be recruited through four public hospitals in the Community of Madrid. Eligible individuals must be adults diagnosed with schizophrenia or bipolar disorder, registered in the digital patient portal, and have active antipsychotic prescriptions. Patients unable to provide informed consent or without portal access will be excluded. Consent will be obtained electronically.

The estimated eligible population is approximately 4,900 individuals. Expected questionnaire completion is ~30%, yielding ~1,640 participants for the validation component. Based on expected non-adherence rates (40-50%), approximately 650 participants are anticipated for the intervention phase.

Data Sources and Security Adherence outcomes will include digital self-report measures (Morisky-Green and Haynes-Sackett) and percentage of antipsychotic exposure obtained from the MUP over the prior six-month period. Sociodemographic and clinical characteristics (age, sex, urbanicity, comorbidities) will be extracted from the Patient Portal.

Personal identifiers will be pseudonymized and stored separately from study records. Access to data will be restricted to authorized study personnel. Digital infrastructure includes encrypted communication, firewalls, intrusion-detection systems, and periodic audit mechanisms. Data processing follows GDPR and Spanish data protection laws.

Statistical Plan Analyses will employ SPSS and R. For the validation phase, diagnostic accuracy metrics and ROC curves will be calculated. For risk-factor analysis, logistic regression (using <75% exposure as a risk threshold) and correlation analyses will be performed. For intervention evaluation, pre-post comparisons of pharmacological exposure and questionnaire scores will be conducted using appropriate paired statistical tests.

Risks and Burden The intervention consists of group psychoeducational telehealth sessions, with no known risks. Participants will not receive financial incentives. Data confidentiality and voluntary participation are ensured.

Study Relevance To our knowledge, this is the first Spanish study validating digital adherence questionnaires against real-world electronic dispensing data in patients with severe mental illness, and one of the first to integrate digital phenotyping with a peer-supported telehealth adherence program. The findings may support scalable, patient-centered models to improve adherence and long-term outcomes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1640

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis established using ICD-11 clinical criteria [15].
  • Aged 18 years or older.
  • Registered on the Patient Portal.
  • With an active prescription for antipsychotic drugs in the MUP (Medication Use Profile).

Exclusion Criteria:

  • Aged under 18 years old.
  • Unable to provide consent for medical or legal reasons.
  • Not registered on the Patient Portal.
  • No active prescription for antipsychotic drugs in the MUP.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Patients with adherence problems in antipsychotic treatment
Pre-post comparison of participants identified with reduced antipsychotic medication adherence via electronic dispensing records and self-report measures will receive a structured psychoeducational adherence-support program. The intervention consists of ten online group telehealth sessions led by clinical psychologists, including two sessions with trained peer-support contributors who have lived experience of stable recovery. Sessions focus on education about illness and medication, strategies to improve adherence, problem-solving skills, digital medication management tools, and relapse-prevention planning. Participants also receive written psychoeducational materials. Duration: approximately 10 weeks, one session per week.
Behavioral: Telehealth Psychoeducational Adherence Program
Participants with reduced antipsychotic treatment adherence will receive a structured telehealth psychoeducational program designed to improve medication adherence. The program includes 10 weekly online group sessions led by clinical psychologists and two peer-support sessions, focusing on illness and medication education, adherence strategies, problem-solving, digital medication-management tools, and relapse-prevention skills. Participants also receive supportive written materials.
Other Names:
  • ADHERA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Medication adherence measured by the Morisky Medication Adherence Scale (MMAS-7)
Time Frame: Baseline (assessment of adherence over the previous 6 months prior to enrollment)
Score on the 7-item Morisky Medication Adherence Scale (MMAS-7), range 0-7, with lower scores indicating poorer adherence.
Baseline (assessment of adherence over the previous 6 months prior to enrollment)
Antipsychotic medication exposure measured by Medication Use Profile (MUP)
Time Frame: Baseline (medication exposure during the 6 months prior to enrollment)
Percentage of days covered (%) by antipsychotic medication over the 6 months prior to enrollment, calculated using dispensing data from the Single Prescription Module (MUP).
Baseline (medication exposure during the 6 months prior to enrollment)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Validation of digital self-reported adherence against MUP dispensing data
Time Frame: Baseline (comparison of self-reported adherence and dispensing data for the 6 months prior to enrollment)
Correlation between digital self-reported adherence questionnaire score (specify name, scale range) and percentage of days covered (%) from MUP records.
Baseline (comparison of self-reported adherence and dispensing data for the 6 months prior to enrollment)
Correlation between sociodemographic variables and medication adherence (MMAS-7 score)
Time Frame: baseline
Correlation between sociodemographic variables obtained from the Patient Portal and adherence measured by MMAS-7 score (0-7 scale).
baseline
Correlation between sociodemographic variables and medication exposure (MUP %)
Time Frame: Baseline (6 months prior to enrollment)
Correlation between sociodemographic variables and percentage of days covered (%) by antipsychotic medication based on MUP records.
Baseline (6 months prior to enrollment)
Change in medication adherence after intervention (MMAS-7 score)
Time Frame: Baseline and 6 months post-intervention
Change in MMAS-7 score (range 0-7) from baseline to 6 months post-intervention.
Baseline and 6 months post-intervention
Change in percentage of days covered after intervention (MUP data)
Time Frame: Baseline and 6 months after intervention
Change in percentage of days covered (%) by antipsychotic medication from baseline (6 months prior to enrollment) to 6 months after intervention.
Baseline and 6 months after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hospital Universitario Fundación Jiménez Díaz
Hospital Infanta Elena de Valdemoro, Madrid
Hospital Universitario Rey Juan Carlos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PIC 76-2013_FJD-HIE-HRJC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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