Annotated Bibliography for Migraine Research

Lipton et al.

The research question posted by Lipton et al. 1 focused on the effect of single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura. This research question was of obvious interest to any scholars interested in potential migraine treatments, insofar as the method tested by Lipton et al. represented a novel intervention. The problem addressed in the study was the pain associated with migraine headaches. Single-pulse transcranial magnetic stimulation is not a form of treatment for migraine, but, rather, a means of managing the pain associated with migraine. Lipton et al. used a two-sample posttest design in order to measure the efficacy of treatment with single-pulse transcranial magnetic stimulation. Lipton et al. began with a sample of 276 individuals, sampled from 18 medical centers in the United, and randomly divided the population into a control group and an experimental group. After Lipton et al. excluded those who did not experience migraine with aura and instances of protocol deviation, the original sample was trimmed to 201 individuals. Further trimming due to non-adherence or violated protocol conditions means that the final sub-sample sizes were 71 for the control group and 70 for the control group.  Lipton et al. found that mean proportion of pain-free individuals in the treatment group was significantly (at p < 0.001) higher than the mean proportion of pain-free individuals in the control group at (a) two hours after treatment, (b)24 hours after treatment, and (c) 48 hours after treatment. The differences between the control and experimental group remained statistically significant (at p < 0.001) after adjustment for photophobia, phonophobia, nausea, and other baseline characteristics of the sample. The findings supported the conclusion that the single-pulse transcranial magnetic stimulation was effective for acute treatment of migraine with aura, but only when measured against no form of treatment. The inclusion of other treatment conditions would have improved the quality of the findings.  

Diener et al.

Diener et al.2 posed a research question about the effectiveness and tolerability of topirimate as a treatment for migraines. As a preventive medication, topirimate is fundamentally different from a treatment such as the single-pulse transcranial magnetic stimulation studied by Lipton et al.1, which addresses management of pain after a migraine has already begun. Diener et al. were concerned with the ability of a pharmaceutical solution to prevent the emergence of migraines. Diener et al. employed a randomized, double-blind, placebo-controlled design to measure the effectiveness of topirimate, with the dependent variable being the change in migraine days from a 28-day observation period taking place before the intervention to the 28 days of the intervention period. The experiment was well designed, with appropriate monitoring of adherence to protocol. The study design also included adverse events as a dependent variable. Diener et al. found that the topirimate group experienced 3.5 fewer migraine days as compared to the placebo group. This difference was statistically significant at p < 0.05. However, topirimate use was associated with symptoms including paresthesia, nausea, dyspepsia, fatigue, anorexia, and disturbance in attention.  

Silberstein et al.

Like Diener et al.,2 Silberstein et al.3 posed a research question about the effectiveness and tolerability of topirimate as a treatment for migraines. Silberstein et al. addressed the same problem addressed by Diener et al., that is, the need to learn more about the efficacy of preventive medicines for migraines. Silberstein et al.’s methodology was nearly identical to that of Diener et al. in all respects, rendering the two studies highly comparable.  Silberstein et al. found that topirimate reduced migraine days by 1.7 in direct comparison to the control group; this difference was statistically significant at p = 0.01. However, Diener et al. found that topirimate was associated with a much greater effect—3.5 fewer migraine days—than that found in Silberstein et al.’s study. Moreover, as Silberstein et al. had an observation period that was over three times as long as that of Diener et al., the difference between these two sets of findings is large. While Silberstein et al.’s results triangulate those of Diener et al. in terms of finding topirimate to be effective in reducing migraine; Silberstein et al detected a much smaller effect. 

Wells et al. 

Wells et al.4 posed the following research question: What is the effect of meditation on migraine duration and severity? Wells et al. compared meditation to a group of individuals engaged in treatment as usual. The design of the study was a randomized controlled trial, but the small sample size was an important limitation, as there were only 10 individuals in the experimental group (meditation) and 9 in the control group (treatment as usual). Wells et al. exposed the treatment group to a standardized 8-week intervention designed to improve mindfulness. After the treatment group was exposed to this intervention, headache duration and severity was measured for a 28-day period. Finally, comparisons between the control and treatment group were made.   Wells et al. conceded that their sample was too small to allow for the calculation of statistical significance between groups. Therefore, the results obtained by Wells et al. do not merit discussion.  

Silberstein et al.

Silberstein et al.5 posed the following research question: What is the effect of botulinum toxin type A on migraine prevention? Like Lipton et al.1, Silberstein et al. were interested in preventive rather than treatment effects. Silberstein et al.’s hypothesized means of preventing migraines was the injection of botulinum toxin type A.  Silberstein et al employed a randomized, double-blind, placebo-controlled design to measure the effectiveness of botulinum toxin type A, with the dependent variables being migraine maximum severity, migraine days, migraine vomiting, and adverse effects. The experiment was well designed, with appropriate monitoring of adherence to protocol. Unlike Lipton et al., Silberstein et al. had two levels in the intervention, with a 25 U and a 75 U injection available. The effect of each of these treatment types was measured in the experiment. Silberstein et al. found that the 25 U treatments was more effective, as members of this treatment group experienced significant (at p < 0.05) reduced frequency of migraine attacks, maximum severity of migraines, and reduces instances of vomiting. In addition, members of the 25 U group did not experience adverse effects any more frequently than the members of the control group. Accordingly, 25 U botulinum toxin type A seems to be a promising treatment for migraines.  

Starling and Dodick

Starling and Dodick6 posed the following research question: What are best practices for patients who have chronic migraine? Unlike the other articles considered in this annotated bibliography, Starling and Dodick’s article did not consist of primary research. Rather, Starling and Dodick’s article was closer in form and methodology to a systematic analysis of the literature on migraine treatments. Starling and Dodick reviewed the evidence in favor of the effectiveness of different migraine treatments (in terms of both prevention and post-onset pain management) and evaluated the adverse effects associated with these treatments. The systematic review was, however, short and unaccompanied by a statistical meta-analysis that could have allowed for a more accurate evaluation of the efficacy of the different treatments under consideration. Starling and Dodick also failed to achieve analytical depth in explaining why, according to the literature, certain migraine treatments might be better than others.

References

1. Lipton R, Dodick D, Silberstein S, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurology. 2010;9:373-380.

2. Diener HC, Bussone G, Van Oene J, Lahaye M, Schwalen S, Goadsby P. Topiramate reduces headache days in chronic migraine: a randomized, double‐blind, placebo‐controlled study. Cephalalgia. 2007;27(7):814-823.

3. Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double‐blind, placebo‐controlled trial. Headache: The Journal of Head and Face Pain. 2007;47(2):170-180.

4. Wells RE, Burch R, Paulsen RH, Wayne PM, Houle TT, Loder E. Meditation for migraines: a pilot randomized controlled trial. Headache: The Journal of Head and Face Pain. 2014;54(9):1484-1495.

5. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. Headache: The Journal of Head and Face Pain. 2000;40(6):445-450.

6. Starling A, Dodick D. Best practices for patients with chronic migraine: Burden, diagnosis, and management in primary care. Mayo Clinic Proceedings. 2015;90(3):408-414.