Effect of Venlafaxine Versus Dosulepin in Pain Predominant Somatic Symptom Disorder

NCT06803485 | Recruiting Phase 4

• 1 other identifier: PGThesis/2024-25/108
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Somatic Symptom Disorder (DSM-V)

Keywords

Somatic symptom disorder; Dosulepin; Venlafaxine; Somatic syndrome disorder with pain predominance; Cortisol; TNF alpha

Outcome Measures

Primary Outcomes (1)

• Change in symptoms of Somatic Symptom Disorder using PHQ-15 (Patient health questionnaire) score

  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 Outcomes (5)

• Treatment response rate

  8 weeks

• Change in serum cortisol

  8 weeks

• Change in serum Tumor necrosis factor (TNF) alpha levels

  8 weeks

• Change in quality of life

  8 weeks

• Incidence of treatment-emergent adverse events

  8 weeks

Study Arms (2)

Venlafaxine group

EXPERIMENTAL

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

Dosulepin group

ACTIVE COMPARATOR

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

Interventions

Venlafaxine DRUG

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.

Venlafaxine group

Dosulepin DRUG

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.

Dosulepin group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, 751019, India

RECRUITING

Related Publications (6)

• Miyauchi T, Tokura T, Kimura H, Ito M, Umemura E, Sato Boku A, Nagashima W, Tonoike T, Yamamoto Y, Saito K, Kurita K, Ozaki N. Effect of antidepressant treatment on plasma levels of neuroinflammation-associated molecules in patients with somatic symptom disorder with predominant pain around the orofacial region. Hum Psychopharmacol. 2019 Jul;34(4):e2698. doi: 10.1002/hup.2698. Epub 2019 May 24.

  PMID: 31125145 BACKGROUND

• Park B, Lee S, Jang Y, Park HY. Affective dysfunction mediates the link between neuroimmune markers and the default mode network functional connectivity, and the somatic symptoms in somatic symptom disorder. Brain Behav Immun. 2024 May;118:90-100. doi: 10.1016/j.bbi.2024.02.017. Epub 2024 Feb 13.

  PMID: 38360374 BACKGROUND

• Rief W, Auer C. Cortisol and somatization. Biol Psychol. 2000 May;53(1):13-23. doi: 10.1016/s0301-0511(00)00042-9.

  PMID: 10876062 BACKGROUND

• Kurlansik SL, Maffei MS. Somatic Symptom Disorder. Am Fam Physician. 2016 Jan 1;93(1):49-54.

  PMID: 26760840 BACKGROUND

• D'Souza RS, Hooten WM. Somatic Symptom Disorder. 2023 Mar 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK532253/

  PMID: 30335286 BACKGROUND

• Toussaint A, Kroenke K, Baye F, Lourens S. Comparing the Patient Health Questionnaire - 15 and the Somatic Symptom Scale - 8 as measures of somatic symptom burden. J Psychosom Res. 2017 Oct;101:44-50. doi: 10.1016/j.jpsychores.2017.08.002. Epub 2017 Aug 2.

  PMID: 28867423 BACKGROUND

MeSH Terms

Interventions

Venlafaxine Hydrochloride; Dothiepin

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Dibenzothiepins; Thiepins; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Rituparna Maiti, MD

CONTACT

9438884191; pharm_rituparna@aiimsbhubaneswar.edu.in

Biswa R Mishra, MD

CONTACT

9438884220; psych_biswa@aiimsbhubaneswar.edu.in

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Group Sequential Study Model

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: January 31, 2025
• Study Start: March 11, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available after publication of data and will be for next 5 years.
• 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.

Locations

IN (1)