Effect of Venlafaxine Versus Dosulepin in Pain Predominant Somatic Symptom Disorder

September 19, 2025 updated by: RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar

Effect of Venlafaxine Versus Dosulepin on Clinical Outcomes, Neuroinflammation and Cortisol Level in Pain Predominant Somatic Symptom Disorder: A Group-sequential Randomized Controlled Trial

Somatic symptom disorder (SSD) is marked by persistent physical complaints, often involving pain, alongside excessive thoughts or behaviors related to health, which substantially disrupt daily functioning. The underlying mechanisms of SSD are multifaceted. The serotonin hypothesis links low serotonin levels to the development of somatic symptoms, while the cortisol hypothesis highlights dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, with chronic stress often associated with hypocortisolism. Furthermore, the neuroinflammatory hypothesis suggests that cytokine-driven inflammation and activation of glial cells may intensify pain and somatic symptoms, exacerbating patient outcomes. Challenges such as limited acceptance of the diagnosis, resistance to treatment among patients and caregivers, and societal stigma further hinder effective management.

Currently, treatment options lack definitive efficacy, with pharmacological interventions primarily targeting serotonin pathways. There is limited exploration of therapies addressing mechanisms like cortisol dysregulation and neuroinflammation. Commonly used medications include tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and selective serotonin reuptake inhibitors (SSRIs), with prescribing decisions often based on physician discretion and patient tolerance rather than clear evidence favoring one class over another.

The proposed study aims to compare the efficacy and safety of Dosulepin (a TCA) and Venlafaxine (an SNRI) in managing SSD patients with predominant pain. By evaluating their impact on symptom severity, quality of life, and biomarkers such as serum cortisol and TNF-alpha levels, this research seeks to enhance understanding of SSD treatment. The findings aim to address gaps in SSD pharmacotherapy and contribute to improved patient care strategies.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a primary diagnosis of somatic symptom disorder with pain predominance (DSM-5).
  • Patients of either sex within the age group of 18-65 years.
  • Patients with PHQ-15 score of ≥ 5.
  • All included patients will be treatment-naïve or have not received any treatment in the last 4 weeks.
  • Patients who have given written informed consent.

Exclusion Criteria:

  • A diagnosed psychological condition that might require other treatment (e.g., psychosis, suicidality)
  • Patient undergoing current psychotherapy.
  • Patients with cognitive impairment.
  • History of allergy to either of the study drugs (dosulepin or venlafaxine).
  • Patients with comorbidities like any malignancies, hepatic, renal, cardiovascular, neurological or endocrinal, or respiratory dysfunction.
  • Substance abuse history of psychoactive agents.
  • Pregnant and lactating mothers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venlafaxine group
Venlafaxine will be started at dose of 37.5mg/day in first week and increased to a stable dose of 75 mg/day from second week and will be continued till 8 weeks.
Drug: Venlafaxine
Venlafaxine will be started at a dose of 37.5 mg/day in first week and increased to a stable dose of 75 mg/day from second week and will be continued till 8 weeks.
Active Comparator: Dosulepin group
Dosulepin will be started at dose of 25 mg/day in first week and increased to a stable dose of 50 mg/day from second week and will be continued till 8 weeks.
Drug: Dosulepin
Dosulepin will be started at a dose of 25 mg/day in first week and increased to a stable dose of 50 mg/day from second week and will be continued till 8 weeeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in symptoms of Somatic Symptom Disorder using PHQ-15 (Patient health questionnaire) score
Time Frame: 8 weeks
The PHQ-15 is a freely accessible self-administered somatic symptoms scale that is based on the full Patient Health Questionnaire. Screening for 15 somatic symptoms.Each symptom is scored as 0, 1, or 2, with the total score ranging from 0 to 30. The scores of <5, 5-9, 10-14, and 15-30 indicate minimal, low, moderate, and high symptom levels, respectively.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment response rate
Time Frame: 8 weeks
Treatment response rate (defined as a reduction of ≥ 50% of the PHQ-15 score from baseline) will be evaluated.
8 weeks
Change in serum cortisol
Time Frame: 8 weeks
Change in serum levels of cortisol at baseline after 8 weeks from baseline will be evaluated.The sample will be collected at 8 am.
8 weeks
Change in serum Tumor necrosis factor (TNF) alpha levels
Time Frame: 8 weeks
Change in serum levels of TNF-α after 8 weeks from baseline will be evaluated.
8 weeks
Change in quality of life
Time Frame: 8 weeks
Quality of life will be evaluated using WHO-QOL BREF scores after 8 weeks from baseline. A condensed version of the WHOQOL-100 questionnaire, the WHOQOL-BREF has 26 items. There are four domains, namely, Physical (domain 1), Psychological (domain 2), Social (domain 3), and Environmental (domain 4) in WHOQOL-BREF. Each question will be evaluated on a scale of 1-5. Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life).
8 weeks
Incidence of treatment-emergent adverse events
Time Frame: 8 weeks
The Antidepressant Side-Effect Checklist (ASEC) will be used to evaluate the incidence of adverse events. 21 symptom-specific questions are evaluated on a 0-3 scale with "0" denoting absence, "1" denoting mild, "2" denoting moderate, "3" denoting severe, the final score lies in the range of 0-63. Additionally, the scale determines whether a symptom is associated with antidepressants.
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2025

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

January 27, 2025

First Posted (Actual)

January 31, 2025

Study Record Updates

Last Update Posted (Estimated)

September 24, 2025

Last Update Submitted That Met QC Criteria

September 19, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PGThesis/2024-25/108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) underlying the results of this study will be shared with qualified researchers upon reasonable request. Data will be available after publication and subject to review of a data access proposal and data use agreement.

IPD Sharing Time Frame

Data will be available after publication of data and will be for next 5 years.

IPD Sharing Access Criteria

Data will be shared with qualified researchers upon reasonable request and subject to review of a data access proposal and data use agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Somatic Symptom Disorder (DSM-V)

Clinical Trials on Venlafaxine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe