Topiramate Versus Amitriptyline in Migraine Prevention: A 26-Week, Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Group Noninferiority Trial in Adult Migraineurs

Mayo Clinic Hospital, Phoenix, Arizona 85054, USA.
Clinical Therapeutics (Impact Factor: 2.73). 03/2009; 31(3):542-59. DOI: 10.1016/j.clinthera.2009.03.020
Source: PubMed


The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache.
This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment.
The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ (P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction (P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in +/-5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%).
In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.

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Available from: David W Dodick, Feb 24, 2014
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    • "Topiramate is a popular preventive migraine treatment (Kowacs et al., 2009). Topiramate monotherapy is at least as effective as amitriptyline monotherapy in preventing headaches and improving functionality (Dodick et al., 2009), and it is hypothesized to cause centrally mediated weight loss (Schütt et al., 2010). Topiramate has been suggested as a single-agent short-term adjuvant to exercise and caloric restriction regimens for weight loss in the non-headache population (Bays, 2010). "
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    ABSTRACT: Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogenesis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.
    Frontiers in Neurology 11/2012; 3(article 161):161. DOI:10.3389/fneur.2012.00161
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    • "Consistently strong evidence was found for the positive effect of prophylactic and symptomatic medications. Prophylactic therapies, such as Topiramate [32, 43], Amitriptyline [43] and Botulinum Toxin type A [33], or symptomatic therapies such as Sumatriptan [22, 42] or Almotriptan [26], determine a reduction of headache frequency and intensity but also provide beneficial effects on the reduction of emotional problems associated with migraine, in particular low mood and anxiety [33]. Two studies report limited evidence that complementary non-medical treatments, such as massage therapy [44] and yoga [45], determine a reduction of anxiety and mood problems. "
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    ABSTRACT: Migraine is a common disease which causes significant burden to individuals, in terms of personal suffering and activity reduction, and to societies, in terms of disease cost. The purpose of this study is to identify the most relevant psychosocial difficulties related to migraine, the variables associated with them and the most relevant determinants of their evolution over time. MEDLINE and PsychINFO were searched for studies published in English between 2000 and 2010 that examined psychosocial difficulties in persons with migraine with and without aura, from clinical trials and observational studies. Information on the description of each difficulty, its determinants of onset and change over time and associated variables were extracted and categorized at a higher level. In total, 34 difficulties have been collected from 51 papers: the most frequent were reduced vitality and fatigue, emotional problems, pain, difficulties at work, general physical and mental health, social functioning and global disability. Evidence exists that pharmacological treatments have an impact toward improvement in patients’ difficulties, in particular emotional problems, physical and mental health, difficulties with employment and global disability. Migraine treatments and decreased headaches frequency are the major determinants of improvements in psychosocial difficulties, while no information is available for determinants of worsening; understanding the role of such factors is of primary public health relevance, given the high prevalence and the relevant personal and societal costs of migraine. Electronic supplementary material The online version of this article (doi:10.1007/s10194-012-0482-1) contains supplementary material, which is available to authorized users.
    The Journal of Headache and Pain 09/2012; 13(8). DOI:10.1007/s10194-012-0482-1 · 2.80 Impact Factor
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    • "There is generally little reporting of effect size and its precision, which was only presented in seven abstracts [17, 26, 34, 36–38, 45]. Effect size (active minus control) in percentages or absolute value, with 95% confidence intervals (CI), is the clinically relevant measure. "
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    ABSTRACT: A CONSORT statement on the content of abstracts of randomised, controlled trials (RCTs) was published in 2008. I therefore reviewed the abstracts from 2009 to 2010 published on RCTs in Cephalalgia, Headache and other (non-headache) journals. The following items were reviewed: number of patients, reporting of response either in percentages or absolute values, the use of p values, and effect size with its precision. The latter was recommended in the CONSORT statement. A total of 46 abstracts were reviewed and effect size with 95% confidence intervals was only reported in seven abstracts. The influence of the CONSORT statement on reporting in abstracts has so far only had a limited influence on the headache literature.
    The Journal of Headache and Pain 06/2011; 12(5):505-10. DOI:10.1007/s10194-011-0361-1 · 2.80 Impact Factor
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