Newer Antidepressants in Combination With Pregabalin for Fibromyalgia Syndrome

Comparative Effectiveness of Newer Antidepressants in Combination With Pregabalin for Fibromyalgia Syndrome: A Controlled Randomized Study

Background: The investigator hypothesized that the combined use of pregabalin and paroxetine would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and higher tolerability than amitriptyline or venlafaxine.

Methods: After ethical approval, 75 patients with diagnosed fibromyalgia who were receiving pregabalin 75 mg/day, were randomly allocated to receive amitriptyline 25 mg/day (n = 24), venlafaxine 75 mg/day (n = 25), or paroxetine 25 mg/day (n = 26). All patients were assessed bi-monthly for consequent six months for the changes in the SSS-8, Center for Epidemiological Studies Depression Scale (CESDS), life satisfaction, mood, sleep quality, fatigue and medication tolerability and adverse effects.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Amitriptyline; Drug: Venlafaxine; Drug: Paroxetine

Detailed Description

Fibromyalgia is a common cause of chronic widespread disabling pain affecting 2-5% of the young to middle-aged women in developed countries. The American College of Rheumatology has been established new diagnostic criteria for fibromyalgia in 2010 included a widespread pain index (WPI) and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The definite pathophysiology of chronic pain in fibromyalgia remains unclear.

Fibromyalgia is usually associated with depression, anxiety, and alexithymia increasing over age which contribute significantly to reduced patient wellbeing. These may be due to alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal axis, and disturbances in the dopaminergic and serotonergic systems. Thus the European League Against Rheumatism (EULAR) recommends the use of serotonin and noradrenaline reuptake inhibitors (SNRIs) for the treatment of fibromyalgia, to reduce pain and improve function.

However, few patients achieve satisfactory pain relief with the sole use of SNRIs. A recent Cochrane review demonstrated only modest improvement in relieving pain without reducing of sleep disturbances, fatigue, or the poor quality of life with the use of duloxetine and milnacipran than placebo in patients with fibromyalgia. More patients experienced adverse events like as nausea, dry mouth, constipation, headache, somnolence, dizziness and insomnia leading to stopping medications. Whereas, the evidence from clinical studies shows that combined use of pregabalin and SNRIs such as duloxetine has potential efficacy and better tolerability during the treatment of improvement of pain, fatigue, and sleep disorders in patients with fibromyalgia.

The use of the second-generation antidepressants like as paroxetine (a selective serotonin reuptake inhibitors (SSRIs)) and venlafaxine (SNRIs) may be associated with more tolerability and reduce pain in patients with major depressive disorder.

To the best of the investigator's knowledge, the comparison of the long-term efficacy, tolerability, and safety of the combined use of pregabalin with one of the three antidepressants, namely, amitriptyline, venlafaxine, or paroxetine for the treatment of fibromyalgia has not yet been studied.

The investigators hypothesized that the combined use of pregabalin and paroxetine would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression scales (CESD) and higher tolerability than the use of pregabalin with either amitriptyline or venlafaxine.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fibromyalgia
• Receiving pregabalin daily

Exclusion Criteria:

• Pathologies mimicking the symptoms of fibromyalgia
• Acute systemic inflammatory diseases
• Infections
• Pregnancy
• Lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Amitriptyline; Amitriptyline 25 mg/day	Drug: Amitriptyline; Amitriptyline 25 mg/day
Active Comparator: Venlafaxine; Venlafaxine 75 mg/day	Drug: Venlafaxine; Venlafaxine 75 mg/day
Active Comparator: Paroxetine; Paroxetine 25 mg/day	Drug: Paroxetine; Paroxetine 25 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Somatic Symptoms Scale-8 (SSS-8)	Using the 8-points Somatic Symptoms Score	for six months after start of the medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Center for Epidemiological Studies Depression (CSED)	According to the Center for Epidemiological Studies Depression (CSED) questionnaire	for six months after start of the medication
Life satisfaction	Using a life satisfaction score	for six months after start of the medication
Mood	Using a mood score	for six months after start of the medication
Sleep quality	Using a sleep quality questionnaire	for six months after start of the medication
Fatigue	Using a fatigue questionnaire	for six months after start of the medication
Tolerability	Using a tolerability questionnaire	for six months after start of the medication

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Eiad Ramzy, MD, Lecturer of Anesthesia and Surgical ICU, Mansoura University , Mansoura City, Egypt

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: May 16, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 22, 2015

Study Record Updates

• Last Update Posted (Estimate): May 22, 2015
• Last Update Submitted That Met QC Criteria: May 21, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Fibromyalgia; Pregabalin
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Antidepressive Agents, Tricyclic; Cytochrome P-450 CYP2D6 Inhibitors; Adrenergic Uptake Inhibitors; Paroxetine; Amitriptyline; Venlafaxine Hydrochloride
• Other Study ID Numbers: MUH-ANES-2013-10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No