Somatic Symptom Disorder (DSM-V)Phase 4NCT06803485
Effect of Venlafaxine Versus Dosulepin in Pain Predominant Somatic Symptom Disorder
A Phase 4 study testing Venlafaxine and Dosulepin in people with Somatic Symptom Disorder (DSM-V), run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Somatic Symptom Disorder (DSM-V)
- What is being tested?
- Venlafaxine and Dosulepin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteIndia
- Study dates
- 11 Mar 2025to Nov 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
All India Institute of Medical Sciences (AIIMS)
Bhubaneswar, Odisha, 751019
Rituparna Maiti, MD, 9438884191, pharm_rituparna@aiimsbhubaneswar.edu.in
Biswa R Mishra, MD, 9438884220, psych_biswa@aiimsbhubaneswar.edu.in
About this study
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
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)
- Being tested
- Venlafaxine, Dosulepin
- Keywords
- Somatic symptom disorder, Dosulepin, Venlafaxine, Somatic syndrome disorder with pain predominance, Cortisol, TNF alpha
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenlafaxineDrug
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.
DosulepinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Dosulepin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Secondary outcomes (5)
Treatment response rate
Treatment response rate (defined as a reduction of ≥ 50% of the PHQ-15 score from baseline) will be evaluated.
Measured: 8 weeks
Change in serum cortisol
Change in serum levels of cortisol at baseline after 8 weeks from baseline will be evaluated.The sample will be collected at 8 am.
Measured: 8 weeks
Change in serum Tumor necrosis factor (TNF) alpha levels
Change in serum levels of TNF-α after 8 weeks from baseline will be evaluated.
Measured: 8 weeks
Change in quality of life
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).
Measured: 8 weeks
Incidence of treatment-emergent adverse events
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2025
- Study start11 Mar 2025
- Primary completionAug 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Somatic Symptom Disorder (DSM-V)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group Sequential Study Model
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06803485
- Sponsor's protocol ID
- PGThesis/2024-25/108
- Status last verified
- Sep 2025
- First submitted
- 27 Jan 2025
- Last updated
- 24 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 31125145Park 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.
PubMed 38360374Rief W, Auer C. Cortisol and somatization. Biol Psychol. 2000 May;53(1):13-23. doi: 10.1016/s0301-0511(00)00042-9.
PubMed 10876062Kurlansik SL, Maffei MS. Somatic Symptom Disorder. Am Fam Physician. 2016 Jan 1;93(1):49-54.
PubMed 26760840D'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/
PubMed 30335286Toussaint 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.
PubMed 28867423
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06803485
- Acronym / sponsor ID
- PGThesis/2024-25/108
- Conditions
- Somatic Symptom Disorder (DSM-V)
- Keywords
- Somatic symptom disorder, Dosulepin, Venlafaxine, Somatic syndrome disorder with pain predominance, Cortisol, TNF alpha
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- All India Institute of Medical Sciences, BhubaneswarUniversity, hospital or other
- Study start
- 11 Mar 2025 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 31 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Group Sequential Study Model
| Arm | Type | Receives |
|---|---|---|
| Venlafaxine group | Experimental | Drug: VenlafaxineVenlafaxine 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. |
| Dosulepin group | Active comparator | Drug: DosulepinDosulepin 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenlafaxineVenlafaxine 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 | Venlafaxine group |
| DosulepinDosulepin 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. | Drug | Dosulepin group |
Primary outcome
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.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
- Background: PubMed 31125145Miyauchi 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.
- Background: PubMed 38360374Park 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.
- Background: PubMed 10876062Rief W, Auer C. Cortisol and somatization. Biol Psychol. 2000 May;53(1):13-23. doi: 10.1016/s0301-0511(00)00042-9.
- Background: PubMed 26760840Kurlansik SL, Maffei MS. Somatic Symptom Disorder. Am Fam Physician. 2016 Jan 1;93(1):49-54.
- Background: PubMed 30335286D'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/
- Background: PubMed 28867423Toussaint 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Venlafaxine and Dosulepin in people with Somatic Symptom Disorder (DSM-V), run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rituparna Maiti, MD (9438884191, pharm_rituparna@aiimsbhubaneswar.edu.in), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in symptoms of Somatic Symptom Disorder using PHQ-15 (Patient health questionnaire) score (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06803485, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.