Painhunting Therapy for Interpersonal Event Related Depression (PH-GRIEF)

Efficacy of Painhunting Therapy for Event-Related Depression: A Waitlist-Controlled Randomized Pilot Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Complicated Grief; Loss-Related Depression; Interpersonal Loss
• Intervention / Treatment: Behavioral: Painhunting Therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kazakhstan
  • Astana
    • Astana, Astana, Kazakhstan, 010000
      • Painhunting Research Center

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Experimental - Painhunting Therapy; 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.	Behavioral: Painhunting Therapy; Painhunting therapy is a structured psychotherapeutic intervention designed to identify emotionally significant past experiences associated with current psychological distress and facilitate emotional processing of these experiences. The intervention consists of three individual sessions delivered over 3-4 weeks by trained practitioners.
No Intervention: No Intervention - Waitlist Control; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PHQ-9 (Patient Health Questionnaire-9) Score	PHQ-9 (Patient Health Questionnaire-9) at Time 2 (2 weeks post-randomization), adjusted for baseline PHQ-9 (T0) and language preference covariate using ANCOVA. Scale range 0 to 27; higher scores indicate greater depressive symptom severity. Measurement: participant self-report. Change from prior posting: The prior registry record listed PHQ-9 and ICG as co-primary outcomes. Amendment 3 removed ICG from the primary outcome position. The Statistical Analysis Plan (SAP v1.1, preregistered on OSF) designates PHQ-9 at T2 as the sole primary outcome, with ICG at T2 as the leading secondary outcome. This narrowing of the primary hypothesis was locked prior to examination of any between-group T2 outcome data. Rationale: (a) the PHQ-9 recall-window bias direction is conservative for a two-week T2 (the treatment arm score reflects a mixture of pre-treatment and post-treatment experience, which works against the effect, not for it); (b) empirical administration of the GIC in early T2 assessments	Baseline (T0) to post-treatment/end of wait (T2, approximately week 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of Treatment Gains in PHQ-9 and ICG Scores	Maintenance of treatment gains as measured by change in Patient Health Questionnaire-9 (PHQ-9) and Inventory of Complicated Grief (ICG) scores from post-treatment (T2) to 3-month follow-up (T3). PHQ-9 is a self-report measure of depression severity (range 0-27), with higher scores indicating more severe depression. ICG is a self-report measure of complicated grief symptoms (range 0-76), with higher scores indicating more severe grief.	Post-treatment (T2) to 3-month follow-up (T3, approximately week 16)
Change in GAD-7 Score (Anxiety)	Change in Generalized Anxiety Disorder-7 (GAD-7) Score Self-report measure of anxiety severity (range 0-21). Higher scores indicate more severe anxiety. Analyzed using ANCOVA adjusted for T0 covariate and language preference.	Time Frame: Baseline (T0) to post-treatment/end of wait (T2, approximately week 2)
Change in ICG (Inventory of Complicated Grief) Score	Self-report measure of complicated grief symptoms (range 0-76). Scores of 25 or higher indicate clinically significant complicated grief. Analyzed using ANCOVA adjusted for T0 covariate and language preference.	Baseline (T0) to post-treatment/end of wait (T2, approximately week 2)
Change in WHO-DAS 2.0 12-Item Score (Functional Disability)	Change in World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0) 12-item Score Measure of functional disability (range 12-60). Higher scores indicate greater disability. Analyzed using ANCOVA adjusted for T0 covariate and language preference.	Baseline (T0) to post-treatment/end of wait (T2, approximately week 2)
GIC (Global Impression of Change) at T2	Single-item measure of overall perceived change since study enrollment, rated on a 7-point scale (1 = very much improved to 7 = very much worse). Administered in two parallel versions: participant self-report and independent therapist rating, completed before viewing participant response. Analyzed descriptively with ordinal regression.	2 weeks post-randomization (T2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Credibility/Expectancy Questionnaire (CEQ)	Credibility/Expectancy Questionnaire (CEQ) Score Measure of treatment credibility and expectancy (range varies by subscale). Higher scores indicate greater perceived credibility and expectancy.	Baseline
Working Alliance Inventory - Short Revised (WAI-SR)	Working Alliance Inventory - Short Revised (WAI-SR) Score Measure of therapeutic alliance (range 12-84). Higher scores indicate stronger therapeutic alliance.	After session 1 (Approximately Week 1)
Session Mechanism Checklist	Brief therapist-rated and client-rated checklist documenting which Painhunting therapeutic mechanisms were engaged in each session, based on the Paper 2 framework. Psychometric properties reported descriptively.	After each therapy session (up to 6 sessions), over approximately 4 weeks
Chain-of-Loss Documentation	Structured therapist record documenting the sequence of loss-related events identified during each therapy session. Analyzed descriptively.	After each therapy session (up to 6 sessions), over approximately 4 weeks
Therapist Assessment Form (Midpoint)	3-item structured therapist evaluation completed at end of session 3. Assesses root trauma access, clinical progress, and continuation recommendation. Used to determine eligibility for Phase 2 (additional sessions).	End of session 3 (week 2)
General Self-Efficacy Scale (GSE)	10-item self-report measure of perceived self-efficacy (Schwarzer & Jerusalem, 1995). Administered at baseline only. Analyzed as a pre-specified moderator of PHQ-9 treatment response. Not administered at T2.	Baseline (T0) only
Custom Readiness and Agency Items (Seitov 2026)	Four items assessing prior demonstrated agency and readiness for therapeutic engagement, developed by the PI. Items rated on a 1 to 5 Likert scale. Analyzed as exploratory moderators of treatment response.	Baseline (T0) only

Collaborators and Investigators

• Sponsor: Painhunting LLP

Publications and helpful links

Helpful Links

• Statistical Analysis Plan (SAP v1.1) and preregistration materials

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: March 14, 2026
• First Submitted That Met QC Criteria: March 22, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Randomized Controlled Trial; Psychotherapy; Complicated Grief; Painhunting Therapy; Interpersonal Loss; Emotional Trauma
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: PH-GRIEF-RCT1-2026-WL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon acceptance of the primary publication, the de-identified analytic dataset, analysis scripts, and Statistical Analysis Plan will be deposited on the Open Science Framework (OSF) under the existing project record for this trial, subject to participant consent and al-Farabi KazNU LEC requirements. A data dictionary will accompany the dataset. Any restrictions will be noted explicitly at the time of deposit.
• IPD Sharing Time Frame: De-identified participant data will become available after publication of the primary study results and will remain available for at least 5 years following publication.
• IPD Sharing Access Criteria: Access to de-identified individual participant data will be granted to qualified researchers upon reasonable request to the Principal Investigator. Requests will be evaluated based on the scientific merit of the proposed research and compliance with ethical and data protection standards.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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