Comparison of Vortioxetine Versus Other Antidepressants With Pregabalin Augmentation in Burning Mouth Syndrome

NCT06025474 | Unknown Phase 3 DMC

• 1 other identifier: 251/19
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The treatment of Burning Mouth Syndrome (BMS) presents a challenge in tailoring appropriate medication for individual patients. Antidepressants have demonstrated efficacy in alleviating symptoms in most cases; however, a subset of patients exhibit limited or no response to these treatments. The augmentation with pregabalin to conventional treatment has shown promising outcomes in relieving pain and improving quality of life in chronic pain conditions. This study aimed to compare the efficacy of vortioxetine with other antidepressants (SSRIs/SNRIs) in combination with pregabalin in a cohort of unresponsive BMS patients and to predict treatment response using clinical data. Methods: A 52-week randomized, open-label, active-controlled study was conducted, enrolling 203 BMS patients previously treated with one antidepressant for 12 weeks and non-responder to the treatment. The study sample have included two groups: Group A (136) received vortioxetine, while Group B (67) received SSRIs/SNRIs. Pregabalin (75mg/day) was added to both groups, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks. Treatment response was assessed by measuring reduction in VAS and SF-MPQ scores (\>50 or 1-2) and HAM-A and HAM-D scores (\>50% or ≤7) at 12, 24, 36 and 52 weeks. Classical logistic regression with a stepwise algorithm and Random Forest machine learning models were used to predict treatment response.

Conditions

Burning Mouth Syndrome

Keywords

Burning mouth syndrome; vortioxetine; pregabalin; Drug Therapy

Outcome Measures

Primary Outcomes (2)

• Visual Analog Scale (VAS)

  The Visual Analog Scale (VAS) (Hayes and Patterson, 1921) is a well-validated unidimensional instrument for the measure of pain intensity (Hawker et al., 2011). The score is determined by measuring the distance on the line between the "no pain" and the mark of a patient mark, providing a range of scores from 0 to 10 (0 = no oral symptoms and 10 = the worst imaginable discomfort).

  4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

• Short-form McGill Pain Questionnaire (SF-MPQ)

  the short form of the McGill Pain Questionnaire (SF-MPQ) is a measure of the quality of pain and is a multidimensional pain questionnaire, which measures the sensory, affective, and evaluative aspects of the perceived pain (Hawker et al., 2011). It comprises 15 items from the original MPQ, each scored from 0 (none) to 3 (severe). The SF-MPQ score is obtained by summing the item scores (range 0-45). There are no established critical cutoff points for the interpretation of the scores and, as for the MPQ, a higher score indicates the worse pain.

  4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

Secondary Outcomes (3)

• Hamilton rating scale for Depression (HAM-D)

  4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

• Hamilton rating scale for Anxiety (HAM-A)

  4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

• Pittsburgh Sleep Quality Index (PSQI)

  4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

Other Outcomes (1)

• Clinical Global Impression Scale - Improvement (CGI-I) and Severity (CGI-S)

  3 times evaluation: time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

Study Arms (6)

Vortioxetine+Pregabalin

EXPERIMENTAL

VO group(20mg)+ PGB (75mg) N= 136 Vortioxetine 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Vortioxetine 20Mg Tab; Drug: Pregabalin 75mg

Paroxetine+Pregabalin

ACTIVE COMPARATOR

P group (20mg) + PGB (75mg); N= 10 Paroxetine 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Paroxetine 20 Mg Oral Tablet; Drug: Pregabalin 75mg

Sertraline+Pregabalin

ACTIVE COMPARATOR

S group (50mg) + PGB (75mg); N= 8 Sertraline 50 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Sertraline 50 MG; Drug: Pregabalin 75mg

Citalopram+Pregabalin

ACTIVE COMPARATOR

C group (20mg)+ PGB (75mg) N= 8 Citalopram 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Citalopram 20mg; Drug: Pregabalin 75mg

Escitalopram+Pregabalin

ACTIVE COMPARATOR

E group (10mg) + PGB (75mg); N= 8 Escitalopram 10 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Escitalopram 10mg; Drug: Pregabalin 75mg

Duloxetine+Pregabalin

ACTIVE COMPARATOR

D group (60mg)+ PGB (75mg) N= 33 Duloxetine 60 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks

Drug: Duloxetine 60 MG; Drug: Pregabalin 75mg

Interventions

Vortioxetine 20Mg Tab DRUG

Encapsulated vortioxetine immediate release tablets, once daily

Also known as: Brintellix

Vortioxetine+Pregabalin

Paroxetine 20 Mg Oral Tablet DRUG

Encapsulated paroxetine tablets, once daily

Paroxetine+Pregabalin

Sertraline 50 MG DRUG

Encapsulated sertraline tablets, once daily

Sertraline+Pregabalin

Citalopram 20mg DRUG

Encapsulated citalopram tablets, once daily

Citalopram+Pregabalin

Escitalopram 10mg DRUG

Encapsulated escitalopram tablets, once daily

Escitalopram+Pregabalin

Duloxetine 60 MG DRUG

Encapsulated duloxetine tablets, once daily

Duloxetine+Pregabalin

Pregabalin 75mg DRUG

Encapsulated pregabalin tablets, once daily

Citalopram+Pregabalin; Duloxetine+Pregabalin; Escitalopram+Pregabalin; Paroxetine+Pregabalin; Sertraline+Pregabalin; Vortioxetine+Pregabalin

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with a confirmed diagnosis of BMS based on the International Classification of Orofacial Pain, 1st edition \[International Classification of Orofacial Pain, 1st edition (ICOP) Cephalalgia, 2020\]
• patients of any race or gender; complaining of oral burning recurring daily for \>2 h per day for \>3 months;
• normal blood test findings (including blood count, blood glucose levels, glycated hemoglobin, serum iron, ferritin and transferrin).
• BMS patients previously treated with one antidepressant for 12 weeks and non-responder to the treatment

You may not qualify if:

• the presence of any disease that could be recognized as a causative factor of BMS,
• a history of a psychiatric disorder or a neurological or organic brain disorder,
• a history of alcohol or substance abuse,
• the presence of Obstructive Sleep Apnea Syndrome (OSAS)
• uncontrolled hypertension, diabetes, HIV, narrow-angle glaucoma, or participants enrolled in other investigational studies.
• participants requiring continued treatment with medications that adversely interact with the study medications (eg, quinolone antibiotics, warfarin, agents inhibiting serotonin reuptake) or with hereditary problems of fructose intolerance, glucose galactose malabsorption, or sucrose isomaltase insufficiency

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

University of Naples Federico II

Napoli, Italia, 80131, Italy

RECRUITING

Related Publications (3)

• Adamo D, Calabria E, Coppola N, Pecoraro G, Mignogna MD. Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update. Ther Adv Psychopharmacol. 2021 Sep 3;11:20451253211034320. doi: 10.1177/20451253211034320. eCollection 2021.

  PMID: 34497709 BACKGROUND

• Adamo D, Pecoraro G, Coppola N, Calabria E, Aria M, Mignogna M. Vortioxetine versus other antidepressants in the treatment of burning mouth syndrome: An open-label randomized trial. Oral Dis. 2021 May;27(4):1022-1041. doi: 10.1111/odi.13602. Epub 2020 Sep 15.

  PMID: 32790904 BACKGROUND

• Adamo D, Canfora F, Pecoraro G, Leuci S, Coppola N, Marenzi G, Ottaviani G, Rupel K, Pellegrini L, Aria M, D'Aniello L, Mignogna MD, Albert U. Vortioxetine versus SSRI/SNRI with Pregabalin Augmentation in Treatment-Resistant Burning Mouth Syndrome: A Prospective Clinical Trial. Curr Neuropharmacol. 2025;23(7):800-819. doi: 10.2174/1570159X22999240729103717.

  PMID: 40016875 DERIVED

MeSH Terms

Conditions

Burning Mouth Syndrome

Interventions

Vortioxetine; Paroxetine; Tablets; Sertraline; Citalopram; Escitalopram; Duloxetine Hydrochloride; Pregabalin

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Dosage Forms; Pharmaceutical Preparations; 1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Propylamines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Daniela Adamo

CONTACT

+39 3925253864; danielaadamo.it@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant

Study Record Dates

• First Submitted: August 29, 2023
• First Posted: September 6, 2023
• Study Start: January 1, 2023
• Primary Completion: October 30, 2023
• Study Completion: July 24, 2024
• Last Updated: September 6, 2023

Record last verified: 2023-08

Locations

IT (1)