Clinical trial NCT06803485: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Somatic Symptom Disorder (DSM-V)
Keywords: Somatic symptom disorder
Dosulepin
Venlafaxine
Somatic syndrome disorder with pain predominance
Cortisol
TNF alpha
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2025-01-31
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group Sequential Study Model
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in symptoms of Somatic Symptom Disorder using PHQ-15 (Patient health questionnaire) score
timeFrame: 8 weeks
Secondary outcomes:
measure: Treatment response rate
timeFrame: 8 weeks
measure: Change in serum cortisol
timeFrame: 8 weeks
measure: Change in serum Tumor necrosis factor (TNF) alpha levels
timeFrame: 8 weeks
measure: Change in quality of life
timeFrame: 8 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences (AIIMS)
state: Odisha
Study officials:
References:
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citation: 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.
citation: Rief W, Auer C. Cortisol and somatization. Biol Psychol. 2000 May;53(1):13-23. doi: 10.1016/s0301-0511(00)00042-9.
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citation: 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/
citation: 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.