Below the abstract, please see the “Plain language summary” of this study.
Anticonvulsants for fibromyalgia.
By Nurcan Üçeyler, et al.
BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Anticonvulsants (antiepileptic drugs) are drugs frequently used for the treatment of chronic pain syndromes.
OBJECTIVES: To assess the benefits and harms of anticonvulsants for treating FM symptoms.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2013), MEDLINE (1966 to August 2013), PsycINFO (1966 to August 2013), SCOPUS (1980 to August 2013) and the reference lists of reviewed articles for published studies and www.clinicaltrials.gov (to August 2013) for unpublished trials.
SELECTION CRITERIA: We selected randomised controlled trials of any formulation of anticonvulsants used for the treatment of people with FM of any age.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion.
MAIN RESULTS: We included eight studies: five with pregabalin and one study each with gabapentin, lacosamide and levetiracetam. A total of 2480 people were included into anticonvulsants groups and 1099 people in placebo groups. The median therapy phase of the studies was 13 weeks.
The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM. The amount and quality of evidence was sufficient to draw definite conclusions on the efficacy and safety of pregabalin in FM. Therefore, we focused on our interpretation of the evidence for pregabalin due to our greater certainty about its effects and its greater relevance to clinical practice.
All pregabalin studies had a low risk of bias.
Reporting a 50% or greater reduction in pain was more frequent with pregabalin use than with a placebo (risk ratio (RR) 1.59; 95% confidence interval (CI) 1.33 to 1.90; number needed to treat for an additional beneficial outcome (NNTB) 12; 95% CI 9 to 21).
The number of people who reported being 'much' or 'very much' improved was higher with pregabalin than with placebo (RR 1.38; 95% CI 1.23 to 1.55; NNTB 9; 95% CI 7 to 15).
Pregabalin did not substantially reduce fatigue (SMD -0.17; 95% CI -0.25 to -0.09; 2.7% absolute improvement on a 1 to 50 scale) compared with placebo.
Pregabalin had a small benefit over placebo in reducing sleep problems by 6.2% fewer points on a scale of 0 to 100 (standardised mean difference (SMD) -0.35; 95% CI -0.43 to -0.27).
The dropout rate due to adverse events was higher with pregabalin use than with placebo use (RR 1.68; 95% CI 1.36 to 2.07; number needed to treat for an additional harmful outcome (NNTH) 13; 95% CI 9 to 23).
There was no significant difference in serious adverse events between pregabalin and placebo use (RR 1.03; 95% CI 0.71 to 1.49).
Dizziness was reported as an adverse event more frequently with pregabalin use than with placebo use (RR 3.77; 95% CI 3.06 to 4.63; NNTH 4; 95% CI 3 to 5).
AUTHORS' CONCLUSIONS: The anticonvulsant, pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep problems. Pregabalin use was shown not to substantially reduce fatigue compared with placebo. Study dropout rates due to adverse events were higher with pregabalin use compared with placebo. Dizziness was a particularly frequent adverse event seen with pregabalin use. At the time of writing this review, pregabalin is the only anticonvulsant drug approved for treating FM in the US and in 25 other non-European countries. However, pregabalin has not been approved for treating FM in Europe. The amount and quality of evidence were insufficient to draw definite conclusions on the efficacy and safety of gabapentin, lacosamide and levetiracetam in FM.
Plain language summary – Anticonvulsants for fibromyalgia
Researchers in The Cochrane Collaboration conducted a review of research about the effects of anticonvulsants (antiepileptic drugs) on fibromyalgia (FM). After searching for all relevant studies, they found eight studies with up to 3579 people. The anticonvulsants that they studied were gabapentin, lacosamide, levetiracetam and pregabalin. They found reliable conclusions for pregabalin only.
Key results: pregabalin compared with fake medication after an average of 13 weeks
Pregabalin slightly reduces pain and sleep problems. Pregabalin slightly reduces fatigue. Pregabalin increases medication side effects, in particular dizziness. Pregabalin does not differ from fake medication in serious side effects.
Possible side effects may include drowsiness, weight gain, swelling in the legs, blurred vision and co-ordination problems. Rare complications may include angio-oedema (swelling that happens just below the surface of the skin, most often around the lips and eyes), allergies and diseases of the immune system, worsening of heart failure, impairment of a person's ability to drive or operate machinery, and abuse or dependency on pregabalin. Serious side effects, such as suicidal thoughts, are very rare.
What is FM and what are anticonvulsants?
People with FM suffer from chronic widespread pain, sleep problems and fatigue. There is no cure for FM at present. Treatments aim at relieving the symptoms and improving quality of life.
Anticonvulsants are medications which help people with epileptic seizures. Neurons are cells that send messages to the brain. For example some neurons send messages about light, sound or touch to the brain. If something goes wrong and the neurons send too many messages quickly, then people may feel pain more strongly. Anticonvulsants can help slow the neurons down in the spinal cord and the brain. Some anticonvulsants can reduce pain and sleep problems in chronic pain due to nerve damage and can stabilize mood in people with anxiety and depressive disorders. People with fibromyalgia can have more brain activity and stronger reactions to the stimulus from their senses, so anticonvulsants might help with that. Pregabalin is approved for use in FM patients in most countries of North and South America and Asia, but not in Europe.
Best estimate of what happens to people with FM when they take pregabalin
9 more people out of 100 who took pregabalin reached 50% or greater pain reduction than people who took fake medication (9% absolute improvement).
23 out of 100 people had their pain reduced by 50% or greater when they took pregabalin compared with 14 out of 100 people when they took a fake medication.
11 more people out of 100 who took pregabalin improved 'much' and 'very much' globally than people who took fake medication (12% absolute improvement).
39 out of 100 people improved 'much' and 'very much' globally when they took pregabalin compared with 28 out of 100 people when they took a fake medication.
Fatigue (measured on a 1 to 50 scale):
People who took pregabalin reported a slight reduction of fatigue (2.7% absolute improvement) than people who took a fake medication.
People who took pregabalin rated their fatigue as 34.6 compared with 35.6 in people who took a fake medication.
Sleep problems (measured on a 0 to 100 scale):
People who took pregabalin reported a reduction of sleep problems (6.2% absolute improvement) than people who took a fake medication.
People who took pregabalin rated their sleep problems to be 54.9 compared with 58.6 in people who took fake medication.
Stopping medication due to side effects:
7 more people out of 100 stopped pregabalin compared with fake medication because of side effects (8% absolute deterioration).
18 people out of 100 who took anticonvulsants stopped medication due to side effects compared with 11 people out of 100 who took a fake medication.
Serious side effects:
24 more people out of 100 reported dizziness as a side effect of pregabalin (28% absolute deterioration).
35 people out of 100 who took pregabalin reported dizziness as a side effect compared with 11 people out of 100 who took a fake medication.
Source: Cochrane Database of Systematic Reviews, October 16, 2013. By Nurcan Üçeyler, Claudia Sommer, Brian Walitt, and Winfried Häuser. Department of Neurology, University of Würzburg, Würzburg, Germany, 97080.