Abstract

Background

This review replaces part of an earlier review that evaluated gabapentin for both neuropathic pain and fibromyalgia, now split into separate reviews for the two conditions. This review will consider pain in fibromyalgia only.

Fibromyalgia is associated with widespread pain lasting longer than three months, and is frequently associated with symptoms such as poor sleep, fatigue, depression, and reduced quality of life. Fibromyalgia is more common in women.

Gabapentin is an antiepileptic drug widely licensed for treatment of neuropathic pain. It is not licensed for the treatment of fibromyalgia, but is commonly used because fibromyalgia can respond to the same medicines as neuropathic pain.

Objectives

To assess the analgesic efficacy of gabapentin for fibromyalgia pain in adults and the adverse events associated with its use in clinical trials.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid and Embase via Ovid from inception to 24 May 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.

Selection criteria

Randomised, double‐blind trials of eight weeks' duration or longer for treating fibromyalgia pain in adults, comparing gabapentin with placebo or an active comparator.

Data collection and analysis

Two independent review authors extracted data and assessed trial quality and risk of bias. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.

Main results

Two studies tested gabapentin to treat fibromyalgia pain. One was identified in previous versions of the review and is included here. We identified another study as a conference abstract, with insufficient detail to determine eligibility for inclusion; it is awaiting assessment. The one included study of 150 participants was a 12‐week, multi‐centre, randomised, double‐blind, placebo‐controlled, parallel‐group study using last‐observation‐carried‐forward imputation for withdrawals. The maximum dose was 2400 mg daily. The overall risk of bias was low, except for attrition bias.

At the end of the trial, the outcome of 50% reduction in pain over baseline was not reported. The outcome of 30% or greater reduction in pain over baseline was achieved by 38/75 participants (49%) with gabapentin compared with 23/75 (31%) with placebo (very low quality). A patient global impression of change any category of "better" was achieved by 68/75 (91%) with gabapentin and 35/75 (47%) with placebo (very low quality).

Nineteen participants discontinued the study because of adverse events: 12 in the gabapentin group (16%) and 7 in the placebo group (9%) (very low quality). The number of serious adverse events were not reported, and no deaths were reported (very low quality).

Authors' conclusions

We have only very low quality evidence and are very uncertain about estimates of benefit and harm because of a small amount of data from a single trial. There is insufficient evidence to support or refute the suggestion that gabapentin reduces pain in fibromyalgia.

Author(s)

Tess E Cooper, Sheena Derry, Philip J Wiffen, R Andrew Moore

Abstract

Plain language summary

Gabapentin for pain in adults with fibromyalgia

Bottom Line

There is no good evidence to support or contradict the suggestion that gabapentin at daily doses of 1200 to 2400 mg reduces pain in fibromyalgia.

Background

Fibromyalgia is a complex disorder characterised by widespread pain, fatigue, poor sleep, low mood, and other bodily symptoms. Common pain‐relieving medicines such as paracetamol and ibuprofen are not usually considered effective. Antiepileptic drugs are commonly used to treat fibromyalgia, but there is uncertainty about how good they are.

Gabapentin is a medicine used to treat pain caused by nerves that are not working properly. Gabapentin changes the way that the nerves send messages to the brain. It can be taken in a tablet or a liquid, with or without food. Doses are usually 1200 mg to 2400 mg each day. At the start of treatment low doses are used to minimise side effects, but the dose is usually increased after a few weeks.

Study characteristics

In May 2016 we searched for clinical trials where gabapentin was used to treat pain due to fibromyalgia in adults. We found one study that met the requirements for this review. The study tested 1200 to 2400 mg/day of gabapentin compared with a placebo over 12 weeks, in 150 people.

Key results

The study did not report the number of people with pain reduced by half at the end of week 12. At that time 5 in 10 people taking gabapentin and 3 in 10 taking the placebo had their pain reduced by at least one third. A report of feeling better to any degree was reported by 9 in 10 taking gabapentin and 5 in 10 taking placebo.

About 2 in 10 people taking gabapentin stopped taking the medicine because of side effects, compared with 1 in 10 taking the placebo. The study did not report the number of people with serious side effects, but did report that there were no deaths.

Quality of the evidence

We rated the quality of the evidence as very low because there was only a single small study with important study limitations. Several factors reduced our confidence in the result. Very low quality evidence means that we are very uncertain about the results.

Author(s)

Tess E Cooper, Sheena Derry, Philip J Wiffen, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For people with fibromyalgia

The evidence that gabapentin improves pain or other symptoms of fibromyalgia is weak and of very low quality. At best it may benefit a few people with the condition.

For clinicians

The evidence that gabapentin improves pain or other symptoms of fibromyalgia is weak and of very low quality. At best it may benefit a few people with the condition.

For policy‐makers

Because gabapentin is used widely for neuropathic pain, therapeutic trials may be considered, particularly if it is possible to switch to another drug in place in the event of failure.

For funders

Since no single treatment is effective in a majority of individuals with fibromyalgia, the relatively small number who benefit from gabapentin may be considered worthwhile, particularly if switching rules are in place. The magnitude of benefit in those people who do respond makes studying potential treatments worthwhile, as the benefit can extend to major improvements in quality of life, function, and ability to work (Moore 2010b; Moore 2014b). This probably makes successful treatment of fibromyalgia cost‐effective, as people with moderate or severe chronic pain consume much more health service and non‐health service resources than those with well treated pain (Moore 2014b)

Implications for research 

General

Because the classic trial design of the study included in this review used the LOCFimputation method for study withdrawals, post‐hoc individual participant level analyses using baseline observation carried forward would be regarded as appropriate to strengthen the findings, especially if the pain reduction was linked to improved quality of life and function.

There is, however, a gap between the dosing regimens used in clinical trials, where fairly rapid dose elevations are made over a few weeks, and clinical practice, where dosing increases can be quite slow. Practical research about the most effective use of medicines known to be effective in only a small proportion of patients might be important. Indeed, situations could be envisaged where the degree of recruitment to successful treatment might have a major impact on treating a very difficult, debilitating, and costly condition.

Design

The trial design is generally adequate, but reporting of clinically relevant outcomes using appropriate imputation for withdrawal would improve the relevance of the findings for clinical practice. The comparison of enriched enrolment, randomised withdrawal (EERW) design to classic trial design indicates that good quality EERW designs of long duration may be appropriate for fibromyalgia (Moore 2015).

We know of no obvious design for testing whether differences in initial dosing regimens might produce better overall results, especially flexible dosing regimens over a longer period of time compared with the typically fixed dosing regimens over a shorter period of time as typically used in clinical trials.

Measurement (endpoints)

Assessment of fibromyalgia symptoms should be based on dichotomous participant‐reported outcomes of proven clinical utility. For EERW trials, the end point of maintenance of therapeutic response without withdrawal might be more clearly stated in trial reports, and used as a primary outcome in future trials, including pragmatic trials of dosing regimens.

Comparison between active treatments

Studies involving other treatments, including non‐pharmacological interventions, may be valuable in this context. A multi‐component approach reflects current practice.

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