Painhunting Therapy for Event Related Depression (PH-GRIEF)

Painhunting LLP

Status: Completed

Conditions: Interpersonal Loss; Loss-Related Depression; Complicated Grief

Treatments: Behavioral: Painhunting Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07490691

PH-GRIEF-RCT1-2026-WL

Details and patient eligibility

About

This pilot randomized controlled trial evaluates the efficacy of Painhunting therapy, a brief structured psychotherapy, for adults with depressive symptoms following adverse life events in Kazakhstan. Eighty-four participants with a history of at least one adverse life event documented by the List of Threatening Experiences (LTE, lifetime version) and a baseline PHQ-9 score of 10 or greater were randomized 1:1 to immediate treatment or a waitlist control. The intervention uses an adaptive treat-to-target design: all treatment-arm participants receive three mandatory individual sessions, with up to three additional sessions (maximum six total) for those meeting pre-specified continuation criteria at the midpoint. The primary outcome is depressive symptom severity measured by the PHQ-9 at Time 2 (2 weeks post-randomization). Recruitment closed on April 14, 2026.

Full description

Depressive symptoms following adverse life events (bereavement, divorce, job loss, financial crisis, serious illness, and related events) affect a substantial minority of exposed individuals and are associated with functional impairment and reduced quality of life. Painhunting therapy is a structured psychotherapeutic approach developed by Olzhas Seitov that targets root traumatic incidents underlying persistent distress. Retrospective practice data from 128 cases suggest clinically meaningful symptom improvement, but no controlled trial had been conducted prior to this study.

This trial uses a waitlist-controlled design with stratified block randomization, blinded statistical analysis, and pre-registered analysis (SAP v1.1 preregistered on OSF prior to examination of between-group post-treatment data). The intervention follows an adaptive treat-to-target protocol. Phase 1 consists of three mandatory individual therapy sessions (1.5 to 2 hours each) over three to four weeks. At the end of session 3, participants complete the PHQ-9 and the therapist completes a structured Therapist Assessment Form. Participants meeting both pre-specified continuation criteria (PHQ-9 at or above 10 or less than 50 percent reduction from baseline; and therapist assessment that the root traumatic incident has not been accessed) proceed to Phase 2, receiving up to three additional sessions (maximum six total). Participants not meeting continuation criteria conclude treatment after session 3.

Eligibility uses the LTE (lifetime version) as the adverse life event documentation instrument, with a PHQ-9 severity threshold of 10 or greater serving as the primary clinical gate. Baseline measures include the General Self-Efficacy Scale (GSE, 10 items, administered at T0 only) and four custom readiness items (Seitov 2026), analyzed as pre-specified treatment-response moderators rather than eligibility criteria or T2 outcomes.

The study is coordinated from Astana, Kazakhstan, with sessions delivered in person or via secure video conferencing. Assessment and therapy are conducted in Russian and Kazakh; language preference is captured at enrollment and included as an analytic covariate in the primary and secondary outcome analyses.

Final enrollment: 84 participants randomized, 42 per arm, in 1:1 allocation. Stratified by baseline PHQ-9 severity band and age category; language preference recorded as analytic covariate. Recruitment closed April 14, 2026. Sample size justification: ANCOVA with baseline PHQ-9 as covariate, r = 0.5, two-tailed alpha 0.05, 80 percent power detects a standardized mean difference of d = 0.53 or larger at n = 42 per arm. Usable completer analysis sets of 40 (Group A) and 34 (Group B) after post-randomization attrition retain 80 percent power to detect d = 0.58 or larger.

Approved by the Local Ethics Committee of al-Farabi Kazakh National University (IRB00010790; Protocol No. IRB-1970), initial approval dated March 5, 2026 (reference №210). Amendments approved: March 12, 2026 letter №213/2 (Amendment 1, protocol title change); April 2, 2026 letter №217 (Amendments 2 and 3 bundled, documentation items and LTE broadening with ICG repositioning); April 9, 2026 letter №218 (Amendment 4, timeline and GIC addition). Approval valid through March 4, 2027.

Screening funnel: 216 applications received; 146 completed screening questionnaire; 122 passed psychometric screening; 84 passed clinical interview and confirmed participation; 84 randomized.

Randomization: 42 to Group A (immediate treatment); 42 to Group B (waitlist). Group A post-randomization disposition: 40 in active therapy; 1 withdrew due to therapist preference; 1 lost to follow-up before first treatment session.

Group B post-randomization disposition: 34 in active waitlist; 1 withdrew due to disclosed concurrent external psychotherapy; 4 lost to follow-up; 3 declined continuation, payment-related.

Intention-to-treat population: all 84 randomized participants, regardless of post-randomization disposition.

Protocol Deviations and Quality Assurance Two methodological issues surfaced during T2 data collection have been addressed analytically and documented here for transparency.

Invalid-assessment retest rule: One Group B participant's first T2 PHQ-9 administration yielded a score that the participant retrospectively attributed to an acute transient mood state unrepresentative of the instrument's two-week recall window. Per SAP Section 10, developed in response to this case and locked prospectively before further T2 data examination, such cases trigger a standardized retest within 24 to 48 hours. The retest score supersedes the original for primary analysis. The original is retained in the dataset with an invalidity flag and enters sensitivity analysis. This rule is bilateral (either arm, either direction of implied bias) and is invoked by the study coordinator.

Concurrent training program exposure: One Group B participant was identified as concurrently attending a Painhunting training program, a potential co-intervention. An audit of all 74 active participants for concurrent or prior Painhunting training, workshop, reading-group, or educational program exposure is being conducted. Any documented exposure is retained in the intention-to-treat population and excluded from the per-protocol secondary analysis. A concurrent-training exclusion criterion has been added (Exclusion Criterion 5 above) and will be applied at screening in any subsequent trial.

Statistical Analysis Plan Availability The Statistical Analysis Plan (SAP version 1.1, dated April 16, 2026) is preregistered on the Open Science Framework (OSF) for this project. The SAP was finalized prior to examination of any between-group Time 2 outcome data. SAP v1.1 differs from v1.0 only in reclassifying the General Self-Efficacy Scale as a T0-only moderator rather than a T2 secondary outcome. The SAP supersedes Section 10 of the Study Protocol version 2 (February 21, 2026); where the two conflict, the SAP governs.

Therapy Delivery Staff Seven trained Painhunting therapists deliver treatment. Therapist assignment is tracked as a variable and modeled as a random effect in supplementary mixed-effects analyses.

Enrollment: 84 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adults aged 18 years or older.
2. History of at least one adverse life event documented by the List of Threatening Experiences (LTE, lifetime version, Brugha et al., 1985).
3. PHQ-9 score of 10 or above at screening.
4. Able to attend therapy sessions in person or via secure video.
5. Provides written informed consent.

Exclusion criteria

1. Active suicidal ideation with plan (PHQ-9 item 9 score of 3).
2. Current psychotic symptoms.
3. Currently receiving other psychotherapy at enrollment.
4. Substance dependence requiring medical management.
5. Current or concurrent enrollment in any Painhunting training, educational, workshop, or reading-group program during the trial period or the three months preceding enrollment. (Note: this exclusion criterion is being applied retroactively via a documented audit, following surfacing of a single case of concurrent exposure. See 'Protocol Deviations and Quality Assurance' below.) Eligibility rationale: The prior protocol specified interpersonal loss (bereavement, divorce, relationship dissolution) within a 0 to 180 month window. Amendment 3 broadens this to any adverse life event documented by LTE. The LTE is a 12-item instrument designed specifically for depression research, with lifetime-version adaptations validated in multiple populations. Using LTE as the documentation instrument provides a defensible, research-standard definition of adverse life event exposure and removes the artificial narrowing to interpersonal losses alone.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 2 patient groups

Experimental - Painhunting Therapy

Experimental group

Description:

Painhunting Therapy, adaptive. Phase 1 (mandatory): three individual therapy sessions (1.5 to 2 hours each) over three to four weeks using the Painhunting method (OS Method, Replay Method, Repeater Method, 5-Step Diagnostic Algorithm, Confirmation Protocol). Midpoint assessment at end of session 3 using PHQ-9 and the Therapist Assessment Form. Phase 2 (conditional): up to three additional sessions (maximum six total) for participants meeting both continuation criteria described above. Delivered by trained Painhunting therapists, with therapist assignment tracked for random-effects modeling.

Treatment:

Behavioral: Painhunting Therapy

No Intervention - Waitlist Control

No Intervention group

Description:

Waitlist control. Participants wait approximately two weeks (timed to the Time 2 assessment) with brief bi-weekly safety contact and psychoeducational materials. Full treatment is offered after the waiting period per the ethically-required crossover design.