Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults

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.

Author(s)

Mattias Linde, Wim M Mulleners, Edward P Chronicle, Douglas C McCrory

Abstract

Plain language summary

Gabapentin or pregabalin for preventing migraine attacks in adults

Various medicines, collectively termed 'antiepileptics', are used to treat epilepsy. For several years, some of these drugs have also been used for preventing migraine attacks. For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of gabapentin and two related drugs (pregabalin and gabapentin enacarbil) in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013, along with three unpublished and previously confidential drug company research reports, and found six relevant studies, five of gabapentin and one of gabapentin enacarbil, both over a wide dose range. The studies showed that neither gabapentin nor gabapentin enacarbil was more effective than placebo at reducing the frequency of migraine headaches. Gabapentin commonly caused side effects, especially dizziness and somnolence (sleepiness). No studies of pregabalin were identified, and research on this drug is desirable.

Author(s)

Mattias Linde, Wim M Mulleners, Edward P Chronicle, Douglas C McCrory

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The evidence derived from trials of gabapentin suggests that it has little or no beneficial effect in migraine prophylaxis while generating side effects in the majority of patients. It may therefore be advocated that it should not be used in routine clinical practice.

The conclusions in this review cannot be extrapolated to chronic migraine, transformed migraine, or chronic daily headache. None of these conditions was considered for this review, as properly validated definitions are as yet lacking. There is no firm evidence for an effect of pregabalin for the prophylaxis of migraine.

Implications for research 

Published research on gabapentin for migraine prophylaxis has misled clinicians for a number of years. Enquiry is needed into the causes of this, and the harms that may have resulted.

While efficacy for high doses of gabapentin has not been ruled out, the evidence for this drug, overall, is not promising and does not lead us to recommend further studies with any degree of priority.

There are no controlled trials of pregabalin in the prophylaxis of migraine. Well‐designed studies comparing it to placebo and interventions with proven efficacy in migraine are needed.

In general, we feel that the quality of both methods and reporting is disappointing in this area of investigation. In particular, investigators wishing to report intention‐to‐treat analyses should carefully consider the recommendations of medical statisticians (eg, Hollis 1999). Future trialists should also be encouraged to follow the recommendations of the International Headache Society (Tfelt‐Hansen 2012) with regard to both trial design and reporting of data.

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