Table 11Summary of the evidence by key question

Key questionComparisonStrength of evidenceConclusion
1. For adults with fibromyalgia, what is the comparative effectiveness/efficacy of included interventions?
1a. When used as monotherapy?
Direct evidenceImmediate-release paroxetine vs. amitriptylineLowPain: Significantly greater reduction with immediate-release paroxetine
LowFatigue: No significant difference
Insufficient50% response, FIQ mean change: No data available
Cyclobenzaprine vs. amitriptylineLowPain and fatigue: No significant differences
Insufficient50% response, FIQ mean change: No data available
Nortriptyline vs. amitriptylineLowPain and FIQ: No significant differences
Insufficient50% response, FIQ mean change: No data available
Indirect evidenceDuloxetine vs. milnacipranLowPain, sleep disturbance, depressed mood, and HRQOL: Significantly greater improvement with duloxetine
50% response, Fatigue and FIQ mean change: No significant difference
Duloxetine vs. pregabalinLowDepressed mood: Significantly greater improvement with duloxetine
Pain, 50% response, Fatigue, FIQ mean change, SF-36 physical and mental components, sleep disturbance, and HRQOL: No significant difference
Duloxetine vs. amitriptylineLowPain and Fatigue: No significant difference
Insufficient50% response and FIQ mean change: No significant difference
Milnacipran vs. pregabalinLowDepressed mood: Significantly greater improvement with milnacipran
Sleep disturbance: Significantly greater improvement with pregabalin
Pain, 50% response, 30% response, Fatigue, FIQ, and SF-36 physical and mental components: No significant difference
Milnacipran vs. pregabalinInsufficientPGII or PGIC: No significant difference
Milnacipran vs. amitriptylineLowPain, Fatigue: No significant difference
Insufficient50% response, FIQ, and PGII or PGIC: Insufficient data
Pregabalin vs. amitriptylineLowPain, Fatigue: No significant difference
Insufficient50% response, FIQ, and PGII or PGIC: Insufficient data
Gabapentin, cyclobenzaprine, citalopram, fluoxetine, controlled- release paroxetine vs. other drugsInsufficientNo conclusions can be drawn about comparative effectiveness/efficacy because the numbers of trials/patients were too few to provide meaningful results in indirect comparisons
1b. When used as adjunctive therapy?
AllInsufficientNo evidence found
2. For adults with fibromyalgia, what are the comparative harms of included interventions?
2a. When used as monotherapy?
Direct evidenceImmediate-release paroxetine vs. amitriptylineLowOverall AE: Significantly greater with amitriptyline
LowWithdrawals due to adverse events: No significant difference
Cyclobenzaprine vs. amitriptylineModerateOverall AE: No significant difference
LowWithdrawals due to adverse events: No significant difference
Nortriptyline vs. amitriptylineModerateOverall AE: Significantly greater with nortriptyline
LowWithdrawals due to adverse events: No significant difference
Indirect evidenceDuloxetine vs. milnacipranLowOverall withdrawal, overall adverse events, and withdrawal due to adverse events: No significant difference
Headache and Nausea: No significant difference
Diarrhea: Significantly greater with duloxetine
Duloxetine vs. pregabalinLowOverall withdrawal, overall adverse events, and withdrawal due to adverse events: No significant difference
Headache, Nausea, and Diarrhea: Significantly greater with duloxetine
Duloxetine vs. amitriptylineLowOverall withdrawal: No significant difference
InsufficientOverall adverse events and withdrawal due to adverse events: No significant difference
Milnacipran vs. pregabalinLowOverall withdrawal, overall adverse events, withdrawal due to adverse events, and diarrhea: No significant difference
Headache and nausea: Significantly greater with milnacipran
Milnacipran vs. amitriptylineLowOverall withdrawal: No significant difference
InsufficientOverall adverse events and withdrawal due to adverse events: No significant difference
Pregabalin vs. amitriptylineLowOverall withdrawal: No significant difference
InsufficientOverall adverse events and withdrawal due to adverse events: No significant difference
Gabapentin, cyclobenzaprine, citalopram, fluoxetine, controlled- release paroxetine vs. other drugsInsufficientNo conclusions can be drawn about comparative harms because the numbers of trials/patients were too few to provide meaningful results in indirect comparisons
2b. When used as adjunctive therapy?
AllInsufficientNo evidence found
3. Are there subgroups of patients based on demographics (age, racial or ethnic groups, and gender), socioeconomic status, other medications, or comorbidities for which any included drugs are more effective or associated with fewer harms?
Amitriptyline, cyclobenzaprineLowAge: Response to amitriptyline or cyclobenzaprine did not differ based on age.
OthersInsufficientSex: Efficacy findings (not specified) for cyclobenzaprine were not influenced by sex. However, effect of duloxetine on pain was no longer significant in males.
Race: Race did not influence efficacy for cyclobenzaprine, but pain reduction with duloxetine was significant in white but not nonwhite patients based on a small sample size.
Comorbidities: Compared with placebo, duloxetine, fluoxetine, controlled-release paroxetine, and pregabalin significantly improved fibromyalgia symptoms regardless of baseline depression. Controlled-release paroxetine and pregabalin significantly improved fibromyalgia symptoms regardless of baseline anxiety.

Abbreviations: AE, adverse event; FIQ, Fibromyalgia Impact Questionnaire total score; HRQOL, health-related quality of life; PGII, Patient Global Impression of Improvement; PGIC, Patient Global Impression of Change.

From: Summary

Cover of Drug Class Review: Drugs for Fibromyalgia
Drug Class Review: Drugs for Fibromyalgia: Final Original Report [Internet].
Smith B, Peterson K, Fu R, et al.
Portland (OR): Oregon Health & Science University; 2011 Apr.
Copyright © 2011, Oregon Health & Science University.

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