Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial

Abstract

Fibromyalgia is a syndrome characterized by chronic widespread pain and associated with sleep disturbance, depression, fatigue, and cognitive dysfunction. Polypharmacy is commonly used, but supportive evidence is limited. Most fibromyalgia trials focus primarily on pain reduction with monotherapy. This trial compares a pregabalin-duloxetine combination to each monotherapy. Using a randomized, double-blind, 4-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine, and pregabalin-duloxetine combination-for 6 weeks. Primary outcome was daily pain (0-10); secondary outcomes included global pain relief, Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. Of 41 participants randomized, 39 completed ≥2 treatments. Daily pain during placebo, pregabalin, duloxetine, and combination was 5.1, 5.0, 4.1, and 3.7, respectively (P < 0.05 only for combination vs placebo, and pregabalin). Participants (%) reporting ≥moderate global pain relief were 18%, 39%, 42%, and 68%, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Fibromyalgia Impact Questionnaire scores were 42.9, 37.4, 36.0, and 29.8, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). SF-36 scores were 50.2, 55.7, 56.0, and 61.2, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Medical Outcomes Study Sleep Scale scores were 48.9, 35.2, 46.1, and 32.1, respectively (P < 0.05 only for combination vs placebo, and duloxetine). BDI-II scores were 11.9, 9.9, 10.7, and 8.9, respectively (P < 0.05 only for combination vs placebo). Moderate-severe drowsiness was more frequent during combination vs placebo. Combining pregabalin and duloxetine for fibromyalgia improves multiple clinical outcomes vs monotherapy. Continued research should compare this and other combinations to monotherapy for fibromyalgia.

Treatment of fibromyalgia

“…3,24 The effect sizes for nonpharmacological approaches tend to be larger than those for drugs, but combinations of drugs have only recently started to be tested. There have been some positive results, [25][26][27] emphasising the potential utility of a multimodal approach.…”

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

“…Both pregabalin and duloxetine fibromyalgia clinical trials reveal that the pain relief is not related to alleviation of anxiety or depression symptom [5]. Recently, a clinical study indicates that combination of pregabalin with duloxetine for fibromyalgia increases multiple clinical outcomes [6]. However, there is little guideline on these medicines to manage pain and psychiatric comorbidity in fibromyalgia patients because of divergent comorbid symptoms (e.g.…”

“…Rats were placed on the platform for adaptation to the apparatus for 5-10 min prior to the experimental measurement. Discrete von Frey filaments of varying bending forces (2,4,6,8,10,15, and…”

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“…The use of multiple oral analgesics from different classes gives a more pronounced pain reduction compared to single oral analgesics [26][27][28][29]. Also there is some evidence that combinations of topical (co)analgesics lead to a more pronounced pain reduction compared to topical monotherapy [30][31][32].…”