Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia

Abstract

Background Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co‐exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review. Objectives To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. Search methods For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017. Selection criteria We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults. Data collection and analysis Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health‐related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta‐analysis using a random‐effects model. We assessed the evidence using GRADE and created a 'Summary of findings' table. Main results We added eight new studies with 1979 participants for a total of 18 included studies with 7903 participants. Seven studies investigated duloxetine and nine studies investigated milnacipran against placebo. One study compared desvenlafaxine with placebo and pregabalin. One study compared duloxetine with L‐carnitine. The majority of studies were at unclear or high risk of bias in three to five domains. The quality of evidence of all comparisons of desvenlafaxine, duloxetine and milnacipran versus placebo in studies with a parallel design was low due to concerns about publication bias and indirectness, and very low for serious adverse events due to concerns about...

Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation

“…Additionally, serotonin/noradrenaline reuptake inhibitors (SNRIs; e.g., duloxetine, milnacipran, etc.) are among the most commonly prescribed pharmacological treatments for FM, and show moderate effectiveness in reducing some FM symptoms (Welsch et al, 2018). While the primary mechanism of action of SNRIs is to normalize concentrations of endogenous monoamine neurotransmitters, which are thought to be imbalanced in FM (Albrecht et al, 2016; Kosek et al, 2016; Russell et al, 1992; Wood, 2008), one potential additional mechanism may be glial modulation, as both duloxetine (Yamashita et al, 2016) and milnacipran (Shadfar et al, 2018) attenuate microglial activation in animal models.…”

Advances in Achieving Opioid Analgesia Without Side Effects

“…Clearly, conventional opioids produce numerous side effects, yet they are the strongest painkillers. As all other, non-opioid pain medications also exert adverse actions, none of them produces as powerful pain relief as opioids ( Stein and Kopf, 2009 ; Sondergaard and Gislason, 2017 ; Welsch et al, 2018 ). Therefore, opioids will remain the main therapy for moderate and severe pain, which makes efforts to improve their action profile highly desirable and relevant.…”

Fibromyalgia

“…Дулоксетин в нескольких рандомизированных контролируемых исследованиях (РКИ) показал преимущество перед плацебо в купировании боли и уменьшении симптомов депрессии, однако не влиял на степень выраженности утомляемости и нарушений сна. Дулоксетин для лечения ФМ рекомендуют назначать в дозе 60 мг/сут [54,55].…”

“…Милнаципран по сравнению с плацебо показал статистически значимо более высокую эффективность в отношении уменьшения интенсивности боли и снижения выраженности утомляемости, в меньшей степени препарат влиял на симптомы депрессии и нарушения сна. При ФМ эффективные дозы милнацпрана составляют 100-200 мг/ сут [55,56].…”