General Practitioner & Pharmacist Support for Discontinuing Long-term Antidepressants in Clinically Stable Patients (GPS-AD)

General Practitioner & Pharmacist Support for Discontinuing Long-term Antidepressants in Clinically Stable Patients: a Cluster Randomised Pragmatic Trial in Primary Care

In Belgium, many adults who have suffered from depression keep using antidepressants on a daily basis for years afterwards, sometimes longer than guidelines recommend. Yet for some people who have been feeling well for a long time, this is no longer necessary, while the continued use of antidepressants can lead to side effects and causes additional costs for the healthcare system.

However, reducing the doses of antidepressants or stopping altogether is not always easy. Some patients are afraid that their depression will return, and GPs and pharmacists often find the subject difficult to broach.

This is why the GPS-AD study is investigating a new approach in which GPs and pharmacists work more closely together to provide better support to patients. First, the GP invites patients who have been taking antidepressants for a long time for a consultation. Together, they discuss whether tapering of the medication is reasonable and feasible. If they agree to stop the treatment, the GP draws up a tapering plan tailored to the patient. The pharmacist helps monitor this process, offering advice and support to the patient while the doses are gradually reduced.

The study will extend over a period of two years and will take place in GP practices throughout Belgium. The new approach based on closer collaboration between GPs and pharmacists will be compared to the current standard of care, to determine whether it helps more long-term users to stop taking antidepressants without experiencing a recurrence of depressive symptoms.

The name of the study, GPS-AD (General Practitioner and Pharmacist Support for Antidepressant Discontinuation), refers to the collaboration between GPs and pharmacists in tapering of antidepressants, and also symbolises the support and guidance (the 'GPS') provided to patients and healthcare providers in assessing whether long-term use of antidepressants is still necessary.

Study Overview

• Status: Not yet recruiting
• Conditions: Deprescribing; Primary Care; Discontinuation; Antidepressant; Depression Disorder
• Intervention / Treatment: Behavioral: GPS-AD intervention

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ellen Van Leeuwen, MD, PhD; Phone Number: +32 (0) 498 66 60 30; Email: ellen.vanleeuwen@ugent.be
• Study Contact Backup: Name: Lies Vanderbeken; Email: lies.vanderbeken@ugent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients will be eligible for inclusion in the study if they meet all of the following criteria:

• Are 18 years or older and capable of providing informed consent.
• Have their Global Medical File (GMD) managed by one of the participating GPs.

• Have been prescribed AD (any type) by their GP for the treatment of depression, with:

  • at least 6 months of continuous daily use following a first depressive episode, or
  • at least 2 years of continuous daily use in the context of a relapsed depression/recurrent episode
• Are judged by their GP as no longer meeting the criteria for a current depressive disorder.

Exclusion Criteria:

Patients will be excluded from participation in the study if they meet any of the following criteria:

• AD discontinuation is considered contra-indicated by the treating GP.

• The patient is judged by the GP to be at high risk of relapse. This includes any of the following:

  • Current significant depressive symptoms, defined as a score of ≥12 on the PHQ-9
  • Current significant anxiety symptoms, defined as a score of ≥10 on the Generalised Anxiety Disorder-7 (GAD-7) scale.
  • Current suicidal ideation, defined as a score >0 on item 9 (suicidality) of the PHQ-9.
  • The patient is currently receiving only psychiatric treatment (out- or inpatient) for depression

In addition to the criteria increasing the risk of relapse, the following will also be an exclusion criteria:

• The patient has a current psychiatric comorbidity (e.g. bipolar disorder, psychosis, substance use)
• The patient has a diagnosis of dementia or significant cognitive impairment (assessed by GP judgement) or is living in a nursing home.
• The AD is prescribed for a primary indication other than depression, such as anxiety alone without comorbid depressive disorder, or chronic pain.
• The patient has insufficient language proficiency in Dutch or French to participate in the study procedures (e.g. providing consent, completion of questionnaires, interviews).
• use of trazodon as AD as this is mainly used for sleep problems

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GPS-AD intervention; The GPS-AD intervention is a structured collaboration between GPs and community pharmacists designed to support the safe discontinuation of long-term AD use in clinically stable adults. The intervention incorporates behavioural activation, motivational support, shared decision-making, personalised tapering schedules, and collaborative care. It follows a stepped-care model and clearly defines the roles of both the GP and pharmacist.	Behavioral: GPS-AD intervention; The GPS-AD intervention is a structured collaboration between GPs and community pharmacists designed to support the safe discontinuation of long-term AD use in clinically stable adults. The intervention incorporates behavioural activation, motivational support, shared decision-making, personalised tapering schedules, and collaborative care. It follows a stepped-care model and clearly defines the roles of both the GP and pharmacist. It starts with an invitation letter and educational brochure that encourages patients to book an appointment with their GP to review their AD use. This is followed by at least one consultation with the GP to discuss the option of tapering AD. If the patient is ready, a personalised tapering plan will be started in collaboration with the pharmacist. The pharmacist provides an initiation consultation, including medication review, tapering plan, potential withdrawal symptoms, motivational support, and a closing consultation focused on future coping.; Other Names: AD discontinuation; AD deprescribing
No Intervention: care as usual; The management and follow-up in the usual care arm is at the discretion of GP/pharmacist/patient, following the Belgian depression guideline. Patients in the control group will receive care as usual.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AD discontinuation (superiority)	Proportion of participants who have stopped antidepressant medication for ≥2 consecutive months at the 12-month follow-up assessment, based on participant self-report. This is a binary measure (yes/no).	12 months post-randomisation
Depressive symptom severity (inferiority)	PHQ-9 total score (range 0-27; higher scores indicate more severe depressive symptoms) at 12 months post-randomisation; this is a continuous metric. Difference in baseline-corrected mean between groups will be evaluated, with 95% CI. Non-inferiority will be assessed using a prespecified non-inferiority margin of 2 points. In this trial, we use co-primary endpoints. The trial will conclude effectiveness only if (1) discontinuation is superior and (2) PHQ-9 is non-inferior.	12 months post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AD discontinuation	Proportion of participants who have stopped antidepressant medication for ≥2 consecutive months at the 6-month follow-up assessment, based on participant self-report. This is a binary measure (yes/no) at 6, i.e. short-term, 18 and 24, i.e. long-term, months.	6, 18 and 24 months post-randomisation
Depressive symptom severity	PHQ-9 total score	6, 18 and 24 months post-randomisation
Suicidal ideation	Patient-reported suicidal ideation assessed using item 9 of the Patient Health Questionnaire-9 (PHQ-9), scored 0-3, with higher scores indicating more frequent suicidal thoughts.	6, 12, 18, and 24 months
Health-related quality of life	Health-related quality of life measured using the EQ-5D-5L questionnaire, summarized as a country-specific index value derived from the five dimensions	6, 12, 18 and 24 months
Mental wellbeing	Mental wellbeing assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), with higher total scores indicating better mental wellbeing.	6, 12, 18, and 24 months post-randomisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: adverse effects of AD	Patient-reported adverse effects of antidepressants assessed using the Antidepressant Side-Effect Checklist (ASEC). The ASEC includes 21 predefined side effects	6, 12, 18, 24 months post-randomisation
Safety: relapse or new depressive episode	Occurrence of relapse or new depressive episode during the preceding 6 months, assessed by the GP based on clinical evaluation and electronic health record review (Yes/No).	6, 12, 18 and 24 months post-randomisation
Safety: withdrawal symptoms	Patient-reported antidepressant withdrawal symptoms assessed using an abbreviated version of the Discontinuation Emergent Signs and Symptoms (DESS) questionnaire.	6 and 12 months
Safety: clinician-assessed withdrawal symptoms	GP-reported occurrence of antidepressant withdrawal symptoms during the preceding 6 months, based on clinical evaluation and electronic health record review (Yes/No).	6 and 12 months post-randomisation

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: KU Leuven; University of Liege; Université Catholique de Louvain; Universiteit Antwerpen; Université Libre de Bruxelles; VUB
• Investigators: Principal Investigator: Ellen Van Leeuwen, MD, PhD, University Ghent

Publications and helpful links

Helpful Links

• Trial page created by funder: KCE Trials

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: depression; primary care; antidepressants; deprescribing; tapering; medication review; long-term use; discontinuation; chronic use
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: ONZ-2025-0571; KCE-24 1543 (Other Grant/Funding Number: KCE Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No