Discontinuing Psychotropic Medication Before Psychotherapy for PTSD

NCT07802158 | Not Yet Recruiting

• 1 other identifier: 10.1159/000549259
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Post-traumatic stress disorder (PTSD) is commonly treated with trauma-focused psychotherapy, including prolonged exposure therapy and eye movement desensitization and reprocessing (EMDR). Patients frequently also use psychotropic medications for insomnia, anxiety, or other PTSD-related symptoms. In a previous cohort study of more than 6,000 adults with PTSD treated in 2021-2024 (https://doi.org/10.1159/000549259), psychotropic co-medication was associated with less improvement in PTSD symptoms after adjustment for 27 baseline covariates; the overall association persisted at 6-month follow-up. Antidepressants overall, and amitriptyline and mirtazapine specifically, showed the most consistent associations across sensitivity analyses. Whether discontinuing these medications before psychotherapy improves treatment outcome remains unknown. This policy-driven natural experiment investigates whether tapering and discontinuing selected psychotropic medications before intensive trauma-focused psychotherapy is associated with greater improvement in PTSD symptoms than continuing the same medications during psychotherapy. In late 2026, the same specialized trauma treatment center (PSYTREC) will introduce a revised medication-review policy. Medication use and indication are verified, and amitriptyline, mirtazapine, quetiapine, topiramate, zolpidem, and zopiclone are tapered and discontinued before psychotherapy when prescribed off-label for PTSD-related symptoms and when discontinuation is considered clinically appropriate and safe. Patients treated under the 2026 policy will be compared with similar patients treated in 2021-2024 who used the same medication but continued it during psychotherapy. Statistical adjustment will further account for clinically relevant baseline differences. Sensitivity analyses will assess whether changes in psychotherapy outcomes over calendar time could explain the findings by examining matched patients whose medication management was unaffected by the policy. The main hypothesis is that discontinuation before trauma-focused psychotherapy is associated with greater reduction in PTSD symptoms. Longer-term PTSD outcomes and the clinical feasibility of medication discontinuation will also be evaluated.

Conditions

Post-traumatic Stress Disorder (PTSD)

Keywords

Stress Disorders, Post-Traumatic; Psychotherapy; Antidepressive agents; Anticonvulsants; Antipsychotic Agents; Target Trial Emulation

Outcome Measures

Primary Outcomes (1)

• CAPS-5 Change Score from Pre- to Post-Treatment

  The primary outcome will be the change in PTSD severity on the Dutch CAPS-5, from pre-treatment (past month) to \~10 days post-treatment (past week version). Changes scores were calculated as post-treatment minus pre-treatment. The CAPS-5, a 20-item scale (0-4 per item), is the gold standard for 100 PTSD assessment. Internal consistency was high in the 2021-2024 sample (Cronbach's α = 0.95).

  from pre-treatment (past month) to ~10 days post-treatment (past week version)

Secondary Outcomes (3)

• PCL-5 Change Score (Pre-Treatment vs. 3 Months Post-Treatment)

  Pre-Treatment vs. 3 Months Post-Treatment)

• PCL-5 Change Score (Pre-Treatment vs. 6 Months Post-Treatment)

  Pre-Treatment vs. 6 Months Post-Treatment

• PCL-5 Change Score (Pre-Treatment vs. 12 Months Post-Treatment)

  Pre-Treatment vs. 12 Months Post-Treatment

Other Outcomes (3)

• Success of discontinuation

  Before the initiation of psychotherapy.

• Clinically relevant discontinuation or rebound symptoms

  Before initiation of psychotherapy

• Necessity of using a substitute agent shortly before therapy

  Before initiation of psychotherapy

Study Arms (4)

2026 target-medication discontinuation cohort

Patients treated from September 2026 who are using amitriptyline, mirtazapine, quetiapine, topiramate, zolpidem, and/or zopiclone off-label for PTSD-related symptoms and for whom tapering and discontinuation before trauma-focused psychotherapy is initiated under the revised medication-review policy. Cohort classification is based on initiation of the discontinuation strategy rather than successful completion of tapering. Primary analyses compare patients with historical users of the same specific medication.

2021-2024 target-medication continuation cohort

Historical patients treated in 2021-2024 who were using one or more of the same target medications at the start of trauma-focused psychotherapy. Under the clinical policy in place during this period, these medications were generally continued during psychotherapy. For the primary analyses, patients will be compared with 2026 patients using the same specific target medication.

2026 non-target psychotropic comparator

Patients treated in 2026 who are using psychotropic medication but none of the six target medications and are therefore not subject to the target-medication discontinuation policy. This cohort is used to estimate secular changes in psychotherapy outcomes and as the active comparator in difference-in-differences analyses.

2021-2024 non-target psychotropic comparator

Historical patients treated in 2021-2024 who were using psychotropic medication but none of the six target medications. These patients provide the historical counterpart to the 2026 non-target psychotropic comparator. The two cohorts will be propensity-score matched, including on psychotropic medication use and relevant baseline clinical characteristics.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Chronic post-traumatic stress disorder

You may qualify if:

• Pseudonymized data from patients treated at PSYTREC from late 2026 onwards (after the policy change) that gave written informed consent for the use of their data for research purposes

You may not qualify if:

• Patients who did not give written informed consent

Sponsors & Collaborators

• Academic Centre for Dentistry in Amsterdam: lead
• Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC): collaborator

Related Publications (1)

• Steenen SA, van Westrhenen R, Steenen CC, Klausch LT, De Jongh A. Concomitant Psychotropic Medication Is Associated with Reduced Outcomes of Trauma-Focused Psychotherapy for Post-Traumatic Stress Disorder. Psychother Psychosom. 2025 Nov 10:1-19. doi: 10.1159/000549259. Online ahead of print.

  PMID: 41212824 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Em. prof. dr. Ad de Jongh, DMD PhD

  Academic Centre for Dentistry in Amsterdam

  STUDY CHAIR

Central Study Contacts

Em. prof. dr. Ad de Jongh, DMD PhD

CONTACT

+31(0)85 303 4444; a.d.jongh@acta.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. Ad de Jongh

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 3, 2026
• Study Start: September 1, 2026
• Primary Completion: September 1, 2026
• Study Completion: September 2, 2026
• Last Updated: September 3, 2026

Record last verified: 2026-08