PTSD clinical trials landscape¶
TL;DR — The registry landscape is broad but noisy: a condition query includes studies where PTSD is only an outcome, comorbidity or exploratory subgroup. This page therefore uses live ClinicalTrials.gov v2 records verified on 2026-09-02 and labels transdiagnostic designs. Current directions include digital/primary-care PE, ketamine- or esketamine-enhanced exposure, sleep intervention, moral-injury treatment, neuromodulation, implementation and measurement. Registration is evidence that a study was planned, not evidence of efficacy.
Registry method¶
ClinicalTrials.gov v2 was queried live for PTSD and then filtered manually for PTSD-directed eligibility/intervention. Status is a snapshot dated 2026-09-02.
Interpretation¶
Recruiting does not mean promising; completed does not mean published; publication does not guarantee outcome concordance. Results and papers require separate verification.
Psychotherapy delivery¶
PE Coach, primary-care PE, internet PE, nurse-led PTSD treatment and implementation studies test reach and delivery as much as efficacy (NCT04959695; NCT03711266; NCT05560854; NCT07430657).
Drug-assisted therapy¶
Ketamine/esketamine plus PE studies test an interaction package rather than medication alone (NCT04560660; NCT06795659). Enrollment separates them sharply: the ketamine-enhanced PE trial randomized 73 veterans against midazolam and has a published protocol (NCT04560660; Shiroma 2024, PMID 38729297), whereas the esketamine-plus-massed-PE record closed as completed with an enrollment of 4, which cannot support an efficacy inference of any kind (NCT06795659, live 2026-09-02). The MDMA phase 3 registrations correspond to published trials (NCT03537014, n=100; NCT04077437, n=121) (Mitchell 2021, PMID 33972795) (Mitchell 2023, PMID 37709999). Two drug programmes have reported since the last sweep and belong in the landscape: the methylone (TSND-201) phase 2 trial, completed with 79 enrolled and now published (NCT05741710) (Jones 2026, PMID 41706459), and psilocybin for veterans with treatment-resistant PTSD, an open-label phase 2 study now active-not-recruiting with 15 enrolled and a published pilot report (NCT05554094) (Armstrong 2026, PMID 42533157).
Sleep and moral injury¶
A transdiagnostic sleep-health study explicitly includes PTSD but is not a PTSD-only efficacy trial (NCT06549049). Moral-injury mindfulness is adjacent to PTSD and should not be relabelled a core PTSD trial (NCT05341882).
Design gaps¶
Small samples, inactive controls, functional unblinding, short follow-up, many outcomes and selective publication can exaggerate signals. Registry–publication concordance should be audited, and doing so on 2026-09-02 produced a concrete gap: NCT03539614, the phase 3 prazosin trial built around noradrenergic biomarkers, records an actual primary completion date of 1 January 2026 but has no results publication indexed in PubMed, so the prospective test of the pretreatment-blood-pressure responder hypothesis is complete but unreported.
Scope boundary¶
Studies using PTSD symptoms as a secondary outcome after ICU, pregnancy, surgery or disaster are not automatically PTSD treatment trials.
Quantitative anchors¶
Every row was re-fetched individually from the ClinicalTrials.gov v2 API on 2026-09-02. Enrollment is shown because a registry status alone conceals the difference between a 121-person phase 3 trial and a 4-person one.
| NCT | Status | Phase | Enrolled | Intervention | Source |
|---|---|---|---|---|---|
| NCT03537014 | Completed | 3 | 100 | MDMA-assisted psychotherapy (MAPP1) | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT04077437 | Completed | 3 | 121 | MDMA-assisted psychotherapy (MAPP2) | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT05741710 | Completed | 1/2 | 79 | Methylone (TSND-201) vs placebo | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT04560660 | Completed | 2 | 73 | Ketamine-enhanced prolonged exposure | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT06795659 | Completed | 1/2 | 4 | Esketamine + massed PE | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT03539614 | Active, not recruiting | 3 | 87 | Prazosin vs placebo; noradrenergic biomarkers | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT05554094 | Active, not recruiting | 2 | 15 | Psilocybin, open-label, veterans | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT04959695 | Recruiting | N/A | 124 | PE Coach app + PE vs PE alone | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT07430657 | Recruiting | N/A | 100 | Nurse-led PTSD treatment in primary care | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT06549049 | Not yet recruiting | N/A | 182 | Transdiagnostic sleep intervention (TranS-C) | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT05341882 | Completed | 3 | 75 | Mindfulness vs educational support for moral injury | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT04007666 | Completed | N/A | 148 | CPT implementation, incarcerated population | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT03711266 | Completed | N/A | 35 | PE for primary care in FQHCs | ClinicalTrials.gov v2, live 2026-09-02 |
| NCT05560854 | Completed | N/A | 30 | Internet-delivered prolonged exposure | ClinicalTrials.gov v2, live 2026-09-02 |
Evidence ledger¶
The ledger lists the live-retrieved records used to bound this page. Inclusion does not make every record equally probative; design, population and comparator remain decisive.
| PMID | Year | Evidence contribution | Scope caution |
|---|---|---|---|
| 33972795 | 2021 | MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. | PTSD-specific record; inspect design and population |
| 37709999 | 2023 | MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. | PTSD-specific record; inspect design and population |
| 39741438 | 2025 | MDMA and MDMA-Assisted Therapy. | PTSD-specific record; inspect design and population |
| 29728331 | 2018 | 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. | PTSD-specific record; inspect design and population |
| 41926191 | 2026 | Comparing dropout from cognitive processing therapy versus prolonged exposure: Results from a randomized clinical trial. | PTSD-specific record; inspect design and population |
| 32063234 | 2020 | Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 32284821 | 2020 | Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 34954460 | 2022 | Exposure therapy for PTSD: A meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 32813696 | 2020 | Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 29414272 | 2018 | Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. | PTSD-specific record; inspect design and population |
| 30688367 | 2019 | Moral Injury: An Integrative Review. | Synthesis: preserve included-population and certainty limits |
| 39630422 | 2025 | Psychological Interventions for Pediatric Posttraumatic Stress Disorder: A Systematic Review and Network Meta-Analysis. | Synthesis: preserve included-population and certainty limits |
| 40308104 | 2025 | An Update on Psychotherapy for the Treatment of PTSD. | PTSD-specific record; inspect design and population |
| 38198456 | 2024 | Effects of MDMA-assisted therapy for PTSD on self-experience. | PTSD-specific record; inspect design and population |
| 39078646 | 2024 | Psychedelic Therapy Scrutinized by FDA Advisory Committee? | PTSD-specific record; inspect design and population |
| 33517752 | 2021 | Ketamine for PTSD: Well, Isn't That Special. | PTSD-specific record; inspect design and population |
| 35688992 | 2022 | Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. | PTSD-specific record; inspect design and population |
| 38795401 | 2024 | Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 34992738 | 2021 | Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. | Synthesis: preserve included-population and certainty limits |
| 36613097 | 2022 | The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials. | Synthesis: preserve included-population and certainty limits |
| 26808441 | 2016 | Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? | PTSD-specific record; inspect design and population |
| 21352105 | 2007 | Early intervention for post-traumatic stress disorder. | PTSD-specific record; inspect design and population |
| 26574151 | 2016 | Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. | Synthesis: preserve included-population and certainty limits |
| 29451967 | 2018 | Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. | Synthesis: preserve included-population and certainty limits |
| 34477098 | 2021 | Comparing treatments for post-traumatic stress disorder - a systematic review. | Synthesis: preserve included-population and certainty limits |
| 38729297 | 2024 | Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. | Protocol; not a results paper |
| 41706459 | 2026 | Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial. | Phase 2; sponsor-employed authors; 90% CIs |
| 42533157 | 2026 | Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial. | n=12; open-label pilot |
Interpretation guardrails¶
- Trauma exposure, post-traumatic symptoms, acute stress disorder, DSM-5 PTSD, ICD-11 PTSD and ICD-11 complex PTSD are not interchangeable populations.
- A mixed-anxiety or transdiagnostic estimate is labelled as such; only a source’s PTSD stratum can be treated as a PTSD effect.
- Comorbid depression is measured separately and cross-linked to the depression condition; it is not absorbed into PTSD.
- Waitlist, treatment-as-usual, attention control and active treatment answer different causal questions.
- Registration, statistical significance and diagnostic loss do not respectively prove completion, clinical importance or functional recovery.
- This page synthesizes research and does not provide individual medical advice.
Minimum extraction frame for studies on this topic¶
| Field | What must be retained | Why it changes interpretation |
|---|---|---|
| Diagnostic system | DSM version, ICD version, full/subthreshold | Case mix is not interchangeable |
| Diagnostic method | Structured interview, clinician judgment, self-report cutoff | Screening is not diagnosis |
| Index trauma | Type, timing, repetition, direct/indirect/occupational | Conditional risk and phenotype differ |
| Population | Civilian, veteran, refugee, child/adolescent, mixed | Transportability is empirical |
| Baseline severity | Mean, SD, range and exclusion threshold | Ceiling and floor effects alter change |
| CPTSD status | ITQ/ICD-11 definition and DSO score | Complexity cannot be inferred from trauma count |
| Comorbidity | Depression, GAD, SUD, pain, TBI measured separately | Shared symptoms can distort effects |
| Comparator | Waitlist, usual care, attention, active treatment | The estimand changes with comparator |
| Treatment dose | Sessions offered/attended, duration, homework | Assignment is not exposure |
| Outcome | Symptoms, diagnosis, response, function, sleep | Outcomes are not interchangeable |
| Time point | End point and prespecified follow-up windows | Acute benefit may not persist |
| Missing data | Denominator, reasons, imputation and estimand | Attrition can bias rank and magnitude |
| Adverse events | Definitions, ascertainment and arm-level counts | Absence of reporting is not absence of harm |
| Therapist/context | Training, fidelity, allegiance, setting | Delivery is part of the intervention |
| Funding/conflicts | Sponsor role and analytic independence | Especially material for proprietary packages |
Claims this page does not make¶
- It does not infer PTSD from trauma exposure alone.
- It does not treat a self-report cutoff as equivalent to a structured diagnosis.
- It does not convert a pooled anxiety-disorder effect into a PTSD effect.
- It does not convert a depression outcome in a comorbid sample into a PTSD outcome.
- It does not infer superiority from a statistically significant within-group change.
- It does not infer equivalence from a non-significant between-group test.
- It does not infer effectiveness from trial registration or mechanistic plausibility.
- It does not assume military, civilian, refugee and pediatric estimates transport unchanged.
- It does not average conflicting estimates that use different definitions.
- It does not treat lack of adverse-event reporting as evidence of safety.
Evidence-updating triggers¶
| Trigger | Required response |
|---|---|
| New diagnostic revision | Recalculate which populations prior estimates represent |
| New head-to-head RCT | Compare against active treatment, not only waitlist |
| New individual-participant synthesis | Revisit effect modifiers and transportability |
| Registry status change | Verify results and linked publication before changing conclusions |
| Guideline update | Separate evidence review from panel recommendation |
| Regulatory decision | Record decision date and source; do not infer from efficacy papers |
| Safety signal | Re-extract denominator, ascertainment and exposure time by arm |
| Contradictory replication | Display estimates side by side; do not average definitions |
Evidence updates should preserve the prior estimate and explain why the new study changes—or does not change—the inference.
Open questions¶
- Which completed PTSD-directed registrations remain unpublished after 24 months?
- Which trials include function, adverse events and post-dropout outcome collection? (Harper 2026, PMID 41926191)
- Will independent MDMA replication address expectancy and therapist effects? (Wolfgang 2025, PMID 39741438)
Related pages¶
- mdma-and-psychedelic-assisted-therapy — phase 3 and regulation.
- dropout-and-nonresponse — trial estimands.
- guidelines — pipeline-to-practice threshold.
- early-intervention-and-prevention — prevention registrations.
References¶
- Mitchell JM, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. PMID 33972795
- Mitchell JM, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023;29(10):2473-2480. PMID 37709999
- Wolfgang AS, et al. MDMA and MDMA-Assisted Therapy. Am J Psychiatry. 2025;182(1):79-103. PMID 39741438
- Mithoefer MC, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018;5(6):486-497. PMID 29728331
- Harper KL, et al. Comparing dropout from cognitive processing therapy versus prolonged exposure: Results from a randomized clinical trial. J Consult Clin Psychol. 2026;94(3):140-150. PMID 41926191
- Mavranezouli I, et al. Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis. Psychol Med. 2020;50(4):542-555. PMID 32063234
- Lewis C, et al. Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis. Eur J Psychotraumatol. 2020;11(1):1729633. PMID 32284821
- McLean CP, et al. Exposure therapy for PTSD: A meta-analysis. Clin Psychol Rev. 2022;91:102115. PMID 34954460
- Coventry PA, et al. Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis. PLoS Med. 2020;17(8):e1003262. PMID 32813696
- Raskind MA, et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018;378(6):507-517. PMID 29414272
- Griffin BJ, et al. Moral Injury: An Integrative Review. J Trauma Stress. 2019;32(3):350-362. PMID 30688367
- Hoppen TH, et al. Psychological Interventions for Pediatric Posttraumatic Stress Disorder: A Systematic Review and Network Meta-Analysis. JAMA Psychiatry. 2025;82(2):130-141. PMID 39630422
- Rothbaum BO, et al. An Update on Psychotherapy for the Treatment of PTSD. Am J Psychiatry. 2025;182(5):424-437. PMID 40308104
- van der Kolk BA, et al. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024;19(1):e0295926. PMID 38198456
- Marks M Psychedelic Therapy Scrutinized by FDA Advisory Committee? JAMA. 2024;332(12):963-964. PMID 39078646
- Stein MB, et al. Ketamine for PTSD: Well, Isn't That Special. Am J Psychiatry. 2021;178(2):116-118. PMID 33517752
- Geldenhuys C, et al. Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. CNS Drugs. 2022;36(7):721-737. PMID 35688992
- Lappas AS, et al. Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. Sleep Med. 2024;119:467-479. PMID 38795401
- Hoskins MD, et al. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Eur J Psychotraumatol. 2021;12(1):1802920. PMID 34992738
- Skeie-Larsen M, et al. The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials. Int J Environ Res Public Health. 2022;20(1):777. PMID 36613097
- Giustino TF, et al. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? Neurobiol Learn Mem. 2016;130:26-33. PMID 26808441
- Bryant RA Early intervention for post-traumatic stress disorder. Early Interv Psychiatry. 2007;1(1):19-26. PMID 21352105
- Cusack K, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016;43:128-41. PMID 26574151
- Carpenter JK, et al. Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depress Anxiety. 2018;35(6):502-514. PMID 29451967
- Storm MP, et al. Comparing treatments for post-traumatic stress disorder - a systematic review. Dan Med J. 2021;68(9):A09200643. PMID 34477098
- Shiroma PR, et al. Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. Contemp Clin Trials. 2024;143:107569. PMID 38729297
- Jones A, et al. Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial. JAMA Psychiatry. 2026;83(5):469-477. PMID 41706459
- Armstrong SB, et al. Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial. Commun Med (Lond). 2026;6(1):411. PMID 42533157