Discontinuing Psychotropic Medication Before Psychotherapy for PTSD

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.