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      Review of pharmacological therapies in fibromyalgia syndrome

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          Abstract

          This review addresses the current status of drug therapy for the management of fibromyalgia syndrome (FMS) and is based on interdisciplinary FMS management guidelines, meta-analyses of drug trial data, and observational studies. In the absence of a single gold-standard medication, patients are treated with a variety of drugs from different categories, often with limited evidence. Drug therapy is not mandatory for the management of FMS. Pregabalin, duloxetine, milnacipran, and amitriptyline are the current first-line prescribed agents but have had a mostly modest effect. With only a minority of patients expected to experience substantial benefit, most will discontinue therapy because of either a lack of efficacy or tolerability problems. Many drug treatments have undergone limited study and have had negative results. It is unlikely that these failed pilot trials will undergo future study. However, medications, though imperfect, will continue to be a component of treatment strategy for these patients. Both the potential for medication therapy to relieve symptoms and the potential to cause harm should be carefully considered in their administration.

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          Most cited references43

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          Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.

          Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related policies. Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.
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            Pregabalin for acute and chronic pain in adults.

            Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above. Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
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              Nabilone for the treatment of pain in fibromyalgia.

              A randomized, double-blind, placebo-controlled trial was conducted to determine the benefit of nabilone in pain management and quality of life improvement in 40 patients with fibromyalgia. After a baseline assessment, subjects were titrated up on nabilone, from 0.5 mg PO at bedtime to 1 mg BID over 4 weeks or received a corresponding placebo. At the 2- and 4-week visits, the primary outcome measure, visual analog scale (VAS) for pain, and the secondary outcome measures, number of tender points, the average tender point pain threshold, and the Fibromyalgia Impact Questionnaire (FIQ), were evaluated. After a 4-week washout period, subjects returned for reassessment of the outcome measures. There were no significant differences in population demographics between groups at baseline. There were significant decreases in the VAS (-2.04, P < .02), FIQ (-12.07, P < .02), and anxiety (-1.67, P < .02) in the nabilone treated group at 4 weeks. There were no significant improvements in the placebo group. The treatment group experienced more side effects per person at 2 and 4 weeks (1.58, P < .02 and 1.54, P < .05), respectively. Nabilone appears to be a beneficial, well-tolerated treatment option for fibromyalgia patients, with significant benefits in pain relief and functional improvement. To our knowledge, this is the first randomized, controlled trial to assess the benefit of nabilone, a synthetic cannabinoid, on pain reduction and quality of life improvement in patients with fibromyalgia. As nabilone improved symptoms and was well-tolerated, it may be a useful adjunct for pain management in fibromyalgia.
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                Author and article information

                Contributors
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central
                1478-6354
                1478-6362
                2014
                17 January 2014
                17 July 2014
                : 16
                : 1
                : 201
                Affiliations
                [1 ]Department of Internal Medicine I, Klinikum Saarbrücken, Winterberg 1, D-66119, Saarbrücken, Germany
                [2 ]Department Psychosomatic Medicine and Psychotherapy, Technische Universität München, Langerstr. 3, D-81675, München, Germany
                [3 ]Georgetown University Medical Center, Washington Hospital Center, 110 Irving Street, Washington, DC 20010, USA
                [4 ]Division of Rheumatology, McGill University Health Centre; Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal H3G 1A4, Canada
                [5 ]Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080, Würzburg, Germany
                Article
                ar4441
                10.1186/ar4441
                3979124
                24433463
                80b54319-4b41-44b6-bdab-257d2ec1eaf1
                Copyright © 2014 Häuser et al.; licensee BioMed Central Ltd.

                The licensee has exclusive rights to distribute this article, in any medium, for 6 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 July 2013
                : 9 January 2014
                Categories
                Review

                Orthopedics
                Orthopedics

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