Fibromyalgia

A review of studies of medications used to treat fibromyalgia. Results of interest mainly involved amitriptyline and duloxetine (Cymbalta). James W. Mold, MD, MPH

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Importance: Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.

Objective: To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.

Data sources: Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.

Study selection: Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.

Data extraction and synthesis: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.

Main outcomes and measures: Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.

Results: A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.

Conclusions and relevance: These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.

Author/s:

Farag, H. M., Yunusa, I., Goswami, H., Sultan, I., Doucette, J. A., Eguale, T.

Association of Therapies With Reduced Pain and Improved Quality of Life in Patients With Fibromyalgia: A Systematic Review and Meta-analysis

Devin Evans — Thu, 14 Jan 2021 06:00:00 +0000

Date Added:

January 14, 2021

Journal/Publication:

Journal of the American Medical Association Internal Medicine

Publication Date:

October 26, 2020

Issue:

Volume:

181

Pages:

104-112

URL:

Association of Therapies With Reduced Pain and Improved Quality of Life in Patients With Fibromyalgia: A Systematic Review and Meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2020.5651

Keywords

Fibromyalgia

quality of life

cognitive behavioral therapy

pain management

PMID (1):

33104162

MeSH

Cognitive Behavioral Therapy

This meta-analysis found that cognitive behavioral therapy, antidepressants, and CNS depressants like gabapentin had some effect in the short- and medium-term for relieving pain and/or improving quality of life in patients with fibromyalgia. No other therapies were supported by the current evidence. James W. Mold, MD, MPH

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Importance: Fibromyalgia is a chronic condition that results in a significant burden to individuals and society.

Objective: To investigate the effectiveness of therapies for reducing pain and improving quality of life (QOL) in people with fibromyalgia.

Data sources: Searches were performed in the MEDLINE, Cochrane, Embase, AMED, PsycInfo, and PEDro databases without language or date restrictions on December 11, 2018, and updated on July 15, 2020.

Study selection: All published randomized or quasi-randomized clinical trials that investigated therapies for individuals with fibromyalgia were screened for inclusion.

Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias using the 0 to 10 PEDro scale. Effect sizes for specific therapies were pooled using random-effects models. The quality of evidence was assessed using the Grading of Recommendations Assessment (GRADE) approach.

Main outcomes and measures: Pain intensity measured by the visual analog scale, numerical rating scales, and other valid instruments and QOL measured by the Fibromyalgia Impact Questionnaire.

Results: A total of 224 trials including 29 962 participants were included. High-quality evidence was found in favor of cognitive behavioral therapy (weighted mean difference [WMD], -0.9; 95% CI, -1.4 to -0.3) for pain in the short term and was found in favor of central nervous system depressants (WMD, -1.2 [95% CI, -1.6 to -0.8]) and antidepressants (WMD, -0.5 [95% CI, -0.7 to -0.4]) for pain in the medium term. There was also high-quality evidence in favor of antidepressants (WMD, -6.8 [95% CI, -8.5 to -5.2]) for QOL in the short term and in favor of central nervous system depressants (WMD, -8.7 [95% CI, -11.3 to -6.0]) and antidepressants (WMD, -3.5 [95% CI, -4.5 to -2.5]) in the medium term. However, these associations were small and did not exceed the minimum clinically important change (2 points on an 11-point scale for pain and 14 points on a 101-point scale for QOL). Evidence for long-term outcomes of interventions was lacking.

Conclusions and relevance: This systematic review and meta-analysis suggests that most of the currently available therapies for the management of fibromyalgia are not supported by high-quality evidence. Some therapies may reduce pain and improve QOL in the short to medium term, although the effect size of the associations might not be clinically important to patients.

Author/s:

Mascarenhas, Rodrigo O., Souza, Mateus B., Oliveira, Murilo X., Lacerda, Ana C., Mendonca, Vanessa A., Henschke, Nicholas, Oliveira, Vinicius C.

Duloxetine: Painful Diabetic Neuropathy and Fibromyalgia

Jeffrey Wilson — Wed, 31 Oct 2018 14:30:36 +0000

Date Added:

October 31, 2018

Journal/Publication:

Bandolier Journal

Publisher:

Bandolier

URL:

Duloxetine: painful diabetic neuropathy and fibromyalgia

Type:

Meta-analyses, Reviews, and Guidelines

Keywords

duloxetine hydrochloride

Fibromyalgia

diabetic neuropathies

MeSH

duloxetine hydrochloride

Fibromyalgia

diabetic neuropathies

There is good evidence that duloxetine helps some patients with either chronic neuropathic pain or fibromyalgia; 60mg/day worked just as well as 120mg/day.

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Clinical bottom line

There is good evidence that duloxetine at doses of 60 or 120 mg daily helps some people with painful diabetic neuropathy or fibromyalgia. The NNT for one person to have at least 50% pain relief is about 6. Nausea, somnolence constipation and reduced appetite are common adverse events.

Author/s:

Sultan, Asquad, Gaskell, Helen, Derry, Sheena, Moore, R. Andrew

Amitriptyline for Neuropathic Pain in Adults

Jeffrey Wilson — Wed, 26 Sep 2018 12:59:46 +0000

Date Added:

November 1, 2018

Journal/Publication:

Cochrane Database of Systematic Reviews

Publisher:

Cochrane Library

Publication Date:

July 6, 2015

Issue:

URL:

Amitriptyline for Neuropathic Pain in Adults

Type:

Meta-analyses, Reviews, and Guidelines, Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD008242.pub3

Keywords

PMID (1):

26146793

MeSH

Fibromyalgia

fatigue syndrome, chronic

amitriptyline

neuralgia

Amitriptyline and its less anticholinergic cousin, nortriptyline are probably very effective for some patients with neuropathic pain not due to cancer or HIV disease.

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BACKGROUND:

This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.

OBJECTIVES:

To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials.

SEARCH METHODS:

We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies.

SELECTION CRITERIA:

We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions.

DATA COLLECTION AND ANALYSIS:

We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.

MAIN RESULTS:

We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).

AUTHORS' CONCLUSIONS:

Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.

Author/s:

Moore, R. Andrew, Derry, Sheena, Aldington, Dominic, Cole, Peter, Wiffen, Phillip J.