Combination pharmacotherapy for the treatment of fibromyalgia in adults

Abstract

BackgroundFibromyalgia is a chronic widespread pain condition a ecting millions of people worldwide. Current pharmacotherapies are o en ine ective and poorly tolerated. Combining di erent agents could provide superior pain relief and possibly also fewer side e ects. ObjectivesTo assess the e icacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults. Search methodsWe searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries. Selection criteriaDouble-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain. Data collection and analysisFrom all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of e icacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table. Main resultsWe identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a di erent agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and ca eine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination Combination pharmacotherapy for the treatment of fibromyalgia in adults (Review)

Fibromyalgia

“…Опубликованы данные РКИ, в которых проведена оценка эффективности комбинированной терапии. Наибольшая эффективность в купировании боли при хорошей переносимости показана для трех комбинаций: дулоксетин и прегабалин; мелатонин и амитриптилин; флуоксетин и амитриптилин [68]. К препаратам, не рекомендованным для фармакотерапии ФМ, относят сильные опиоиды, кортикостероиды, гормон роста, ингибиторы моноаминоксидазы и селективные ингибиторы обратного захвата серотонина в силу отсутствия доказательств эффективности и/или наличия высокого риска развития нежелательных явлений [45].…”

Nonopioid drug combinations for cancer pain: protocol for a systematic review

“…In the setting of chronic noncancer pain, a considerable number of trials have evaluated analgesic drug combinations. 10 , 13 – 17 , 20 , 30 , 35 In theory, combinations of 2 mechanistically distinct analgesic drugs may have additive, or sometimes even synergistic, interactions with regards to analgesia, such that a lower dose of each drug would be needed to achieve the same, or possibly greater, analgesic effect, which may also reduce the incidence of adverse effects. 5 , 18 , 29 , 34 In support of this theory, several clinical trials have demonstrated superior pain reduction with certain combinations of analgesic drugs in the setting of chronic noncancer pain treatment.…”

“…5 , 18 , 29 , 34 In support of this theory, several clinical trials have demonstrated superior pain reduction with certain combinations of analgesic drugs in the setting of chronic noncancer pain treatment. 10 , 13 – 17 , 20 , 30 , 35 Of note, several of these trials involved combinations of nonopioid analgesic drugs. 13 , 15 , 20 …”

Pain and Neuropathic Pain in Rheumatic Diseases

“…In addition, the features of peripheral and central pain processing may be exacerbated by inflammation, and disturbed pain processing may be a feature contributing to widespread pain [4,5]. There are many different strategies of pain therapy such as pharmacological and non-pharmacological in patients with rheumatic diseases [6,7]. The approach to reduce pain in clinical trials and practice should be further developed.…”