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

Registration Number
NCT06025474
Lead Sponsor
Federico II University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
203
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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
  • pregnancy and lactation were exclusion criteria, and women of childbearing potential were required to receive a highly effective form of contraception.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Duloxetine+PregabalinDuloxetine 60 MGD 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
Vortioxetine+PregabalinVortioxetine 20Mg TabVO 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
Vortioxetine+PregabalinPregabalin 75mgVO 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
Paroxetine+PregabalinPregabalin 75mgP 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
Sertraline+PregabalinPregabalin 75mgS 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
Citalopram+PregabalinPregabalin 75mgC 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
Escitalopram+PregabalinEscitalopram 10mgE 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
Escitalopram+PregabalinPregabalin 75mgE 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
Duloxetine+PregabalinPregabalin 75mgD 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
Paroxetine+PregabalinParoxetine 20 Mg Oral TabletP 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
Sertraline+PregabalinSertraline 50 MGS 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
Citalopram+PregabalinCitalopram 20mgC 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
Primary Outcome Measures
NameTimeMethod
Visual Analog Scale (VAS)4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

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).

Short-form McGill Pain Questionnaire (SF-MPQ)4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks

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.

Secondary Outcome Measures
NameTimeMethod
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

The HAM-D is a clinician-administered depression assessment scale; it contains 21 items pertaining to the affective field. The scores can range from 0 to 54. A score \> 7 indicates an impairment. The scores in the range of 7-17 indicate a mild depression, the scores between 18 and 24 indicate a moderate depression, and the scores \>24 indicate a severe depression

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

The HAM-A (Hamilton, 1959) is a clinician-administered anxiety assessment scale. It comprises 14 items to measure both psychic anxiety and somatic anxiety. Each item is scored on a scale of 0-4, a total score \<17 indicates a mild severity, 18-24 mild to moderate, and 25-30 moderate to severe (Hamilton, 1967).

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

The PSQI (Buysse et al., 1989) explores the quality of sleep over a 1-month time interval generating seven "component" scores (0-3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction (Carpenter and Andrykowski, 1998). The total score is obtained by the sum of all the sub-scores and ranges between 0 and 21. A total score greater than five discriminates poor sleepers from good sleepers with a high sensitivity (90%-99%) and specificity (84%-87%) (Curcio et al., 2013).

Trial Locations

Locations (1)

University of Naples Federico II

🇮🇹

Napoli, Italia, Italy

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