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Meta-Analysis
. 2013 Jun 24;2013(6):CD010609.
doi: 10.1002/14651858.CD010609.

Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults

Mattias Linde  1 , Wim M Mulleners, Edward P Chronicle, Douglas C McCrory
Affiliations
Meta-Analysis

Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults

Mattias Linde et al. Cochrane Database Syst Rev. .

Abstract

Background: Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.

Objectives: To describe and assess the evidence from controlled trials on the efficacy and tolerability of gabapentin/gabapentin enacarbil or pregabalin for preventing migraine attacks in adult patients with episodic migraine.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.

Selection criteria: Studies were required to be prospective, controlled trials of gabapentin/gabapentin enacarbil or pregabalin taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.

Data collection and analysis: Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between gabapentin and comparator (placebo, active control, or gabapentin in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and numbers needed to treat (NNTs). We also summarised data on adverse events from all single dosage studies and calculated risk differences (RDs) and numbers needed to harm (NNHs).

Main results: Five trials on gabapentin and one trial on its prodrug gabapentin enacarbil met the inclusion criteria; no reports on pregabalin were identified. In total, data from 1009 patients were considered. One trial each of gabapentin 900 mg (53 patients), and gabapentin titrated to 1200 mg (63 patients) and 1800 mg (122 patients) failed to show a statistically significant reduction in headache frequency in the active treatment group as compared to the placebo group, whereas one trial of gabapentin titrated to 1800 to 2400 mg (113 patients) demonstrated a small but statistically significant superiority of active treatment for this outcome (MD -0.80; 95% confidence interval (CI) -1.55 to -0.05). The pooled results of these four studies (MD -0.44; 95% CI -1.43 to 0.56; 351 patients) do not demonstrate a significant difference between gabapentin and placebo. One trial of gabapentin titrated to 1800 mg (122 patients) failed to demonstrate a significant difference between active treatment and placebo in the proportion of responders (OR 0.97; 95% CI 0.45 to 2.11), whereas one trial of gabapentin titrated to 1800 to 2400 mg (113 patients) demonstrated a small but statistically significant superiority of active treatment for this outcome (OR 2.79; 95% CI 1.09 to 7.17). The pooled results of these two studies (OR 1.59; 95% CI 0.57 to 4.46; 235 patients) do not demonstrate a significant difference between gabapentin and placebo. Comparisons from one study (135 patients) suggest that gabapentin 2000 mg is no more effective than gabapentin 1200 mg. One trial of gabapentin enacarbil (523 participants) failed to demonstrate a significant difference versus placebo or between doses for gabapentin enacarbil titrated to between 1200 mg and 3000 mg with regard to proportion of responders; there was also no evidence of a dose-response trend. Adverse events, most notably dizziness and somnolence, were common with gabapentin.

Authors' conclusions: The pooled evidence derived from trials of gabapentin suggests that it is not efficacious for the prophylaxis of episodic migraine in adults. Since adverse events were common among the gabapentin-treated patients, it is advocated that gabapentin should not be used in routine clinical practice. Gabapentin enacarbil is not efficacious for the prophylaxis of episodic migraine in adults. There is no published evidence from controlled trials of pregabalin for the prophylaxis of episodic migraine in adults.

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Conflict of interest statement

Prof Linde: During the process of preparing this review the author received a travel grant from Allergan in Sweden and was involved as an investigator in a clinical trial in Norway sponsored by AstraZeneca and comparing candesartan, propranolol, and placebo in the prophylaxis of migraine.

Dr Mulleners: The author was a paid consultant for the Merck Dutch Migraine Advisory Board and received a speaker's fee from Merck Sharp & Dohme Corp.

Prof Chronicle: Author deceased. During the process of preparing the original review the author was a paid consultant for Johnson & Johnson and NPS Pharmaceuticals in the USA.

Assoc Prof McCrory: During 2008, the author was a paid expert witness for the plaintiffs in a legal action against the manufacturer of Neurontin (gabapentin). In this capacity, he prepared a systematic review examining previously confidential research reports obtained from the manufacturer (through discovery), along with published trial reports of gabapentin for migraine prophylaxis, and testified at trial.

Figures

1
1
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
1.2
1.2. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
1.3
1.3. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 3 Any adverse event.
1.4
1.4. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 4 Asthenia/fatigue.
1.5
1.5. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 5 Dizziness.
1.6
1.6. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 6 Flu syndrome.
1.7
1.7. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 7 Somnolence.
1.8
1.8. Analysis
Comparison 1 Gabapentin versus placebo, Outcome 8 Abnormal thinking.
2.1
2.1. Analysis
Comparison 2 Gabapentin enacarbil (GEn) versus placebo, Outcome 1 Responders (patients with ≥ 50% reduction in headache frequency).
3.1
3.1. Analysis
Comparison 3 Gabapentin dose comparisons, Outcome 1 Headache frequency (post‐treatment).
3.2
3.2. Analysis
Comparison 3 Gabapentin dose comparisons, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
4.1
4.1. Analysis
Comparison 4 Gabapentin enacarbil (GEn) dose comparisons, Outcome 1 Responders (patients with ≥ 50% reduction in headache frequency).
See this image and copyright information in PMC

References

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