Effect of Venlafaxine Versus Dosulepin in Pain Predominant Somatic Symptom Disorder

Official title

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

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Change in symptoms of Somatic Symptom Disorder using PHQ-15 (Patient health questionnaire) score [Time frame: 8 weeks]

Secondary outcome measures (5)

• Treatment response rate [Time frame: 8 weeks]
• Change in serum cortisol [Time frame: 8 weeks]
• Change in serum Tumor necrosis factor (TNF) alpha levels [Time frame: 8 weeks]
• Change in quality of life [Time frame: 8 weeks]
• Incidence of treatment-emergent adverse events [Time frame: 8 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

India · 1 center

• All India Institute of Medical Sciences (AIIMS) — Bhubaneswar

Publications

• 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
• 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
• 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
• Kurlansik SL, Maffei MS. Somatic Symptom Disorder. Am Fam Physician. 2016 Jan 1;93(1):49-54. PMID 26760840
• D'Souza RS, Hooten WM. Somatic Symptom Disorder. 2023 Mar 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK532253/ PMID 30335286
• 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

Identifiers

NCT: NCT06803485 · PGThesis/2024-25/108

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗