Introduction
Migraine is characterized by recurrent moderate to severe headaches and autonomic nervous system symptoms such as aura. The headache pulsates on one side of the head only. Additional symptoms of migraine include sensitivity to light and sound, nausea and vomiting. According to Robbins and Lipton, migraines are caused by both genetic and environmental factors and affect up to 15% of the global population at some point in life.1 Typically, the severe headache persist for over two hours but may last up to three days.
Pathophysiology of Migraines
Migraines are chronic neurovascular disorder. Goadsby asserts that the condition starts in the brain and spreads quickly to the surrounding blood vessels.2 There is no scientific consensus on the neuronal mechanism involved but there is evidence from Goadsby and from Dodick suggesting that high levels of neurotransmitter serotonin (5-hydroxytryptamine) are involved.(2,3) Different parts of the nervous system are involved in generating the pain associated with migraine. The prognosis of migraine varies but the condition is fairly benign and is not fatal. However, the symptoms lead to loss of productivity and can get more severe and more frequent with time. In addition, Schurks, Rist, Bigal et al., have linked migraines with aura to an increased risk of ischemic stroke hence the benign nature of the condition should not be taken lightly.4 Pharmacologic management of acute migraine is centered on the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and the use of Triptans. Some commonly used NSAIDs include ibuprofen, naproxen sodium, flubiprofen, indomethacin and diclofenac potassium while common triptans include sumartriptan, eletriptan and rizatriptan.5-7
Pharmacology of NSAIDs and Triptans
Tepper, Rapoport and Sheftell assert that the mode of action of triptans is through their agonist effect on 5-hydroxytryptamine receptors in the cranial blood vessels.8 This causes a constriction of blood vessels and inhibits the secretion of pro-inflammation neuropeptides such as substance P and CGRP. This relieves pressure in the head and alleviates headaches. Triptans are effective in treating migraine episodes every time they occur but do not offer any preventive properties. The secretion of pro-inflammatory neuropeptides and prostaglandins is an important step in the pathophysiology of migraine headaches. The action of NSAIDs is centered on the preventing the synthesis of prostaglandins by blocking the enzyme cyclooxygenase as given by Pardutz and Sschoenen.9-10
Clinical Evidence on the Safety and Efficacy of NSAIDs and Triptans
Triptans have a higher efficacy than NSAIDs in the treatment of migraine headaches but the use of NSAIDs has persisted long after triptans were introduced due to their cheaper cost and wide availability as over the counter drugs. NSAIDs are analgesics and their use is supported by clinical evidence. Codispoti, Prior, Fu, Harte and Nelson have found that ibuprofen reduces migraine headache and has a low risk of adverse effects.11 Clinical evidence to support the use of diclofenac was found by Derry, Rabbie and More, who also found that diclofenac can be used in pregnant women for the first and second trimester.12
The higher efficacy of triptans in the management of migraines is based on their effectiveness in relieving both pain and other symptoms such as nausea and vomiting.13 Winner, Rother Saper et al. found that sumatripan a typical triptan drug is effective and safe in the treatment of chronic migraine.14 Triptans are not addictive but can cause drug overuse and their side effects on the heart make them unsuitable for use by patients with cardiovascular diseases. The use of both triptans and NSAIDs in the management of migraines is based on evidence of their efficacy. However, in evaluating the suitability of a drug, it is important to compare the efficacy of the drug with its side effects, interaction with other common drugs and costs.
Critical Evaluation of Evidence
The use of Triptans and NSAIDs is supported by clinical evidence. In this section, a critical evaluation of evidence summarized in the previous section will be conducted to appraise the evidence and recommend it for use in clinical practice. The evaluation will be conducted by evaluating different aspects of the study such as study design, inclusion and exclusion criteria, sampling, research limitations, findings and interpretation.
Efficacy and Safety of NSAIDs
The first evidence that is critically evaluated and apprised is by Codispoti, Prior, Fu, Harte and Nelson, and was published in an article titled “Efficacy of nonprescription doses of ibuprofen for treating migraine headache. A randomized controlled trial” published in the Journal of Head and Face pain.11 Ibuprofen is one of the most commonly used NSAID. The research objectives were to evaluate the efficacy and the safety of ibuprofen at a dosage level of 200mg and 400mg in the treatment of chronic migraine compared to placebo and to each other. Efficacy measures were reduction in baseline headache intensity, 2 hours after therapy and reduction of migraine related symptoms.
Study Design
The study was a placebo-controlled, double-blind, randomized clinical trial. Randomized clinical trial is the most effective study design for the determination of the effectiveness of a drug. Randomization eliminates sampling and internal errors while controlling allows the researchers to meet the objectives of the study. From the study design, the study meets scientific rigor as the design makes it possible to meet the study objectives.
Inclusion and Exclusion Criteria
Inclusion and exclusion criteria relate to the study participants and limit the application of the study findings. This is because the study findings cannot be applied to groups or conditions excluded from the study. In this research, the inclusion criteria were, adult participants with a diagnosis of chronic migraine with moderate or severe pain levels, at least one migraine attack every two months and less than six attacks every month in the previous year, ability to differentiate migraine headache from other types of headaches and a history of use of over the counter drugs for the treatment of migraine. In addition, female participants were required to be postmenopausal or to be using a reliable birth control method for more than three months before the study.11 The exclusion criteria for the study were, patients with severe migraines which require bed rest and interfere with performance of daily duties, vomiting in over 20% of the migraine attacks, history of routine headaches, neck or head trauma, alcohol and drug abuse, history of renal and hepatic disease, diabetes, tuberculosis, and psychiatric illness in the year before the study. The inclusion reduces the effects of hidden variables that may affect the study findings thereby increasing the reliability of the results.
Sampling and Randomization
The study was carried out by 15 investigators in 17 private referral centers. 721 outpatient subjects were recruited for the study11 The participants were randomly assigned to three groups. Group one (n=240) was give ibuprofen 200mg, group two (n=241) was given ibuprofen 400mg while group three (n=240) was given placebo. Figure 1.0 shows the profile of the study.
Fig 1.0 Profile of the Study
Study Findings and Interpretation
After two hours 41.7%, 40.8% and 28.15 of participants on 200mg, 400mg and placebo reported mild to no pain. Both doses of ibuprofen provide greater differences in mean pain intensity compared to placebo. Both of the ibuprofen doses were statistically more effective in alleviating secondary symptoms of migraine than placebo. Figure 2.0 shows the percentages of patients with reduced to mild (or none). These results demonstrate that ibuprofen doses at 200mg and at 400mg have high efficacy in treating migraine and are safe to use. In addition to relieving pain, ibuprofen alleviates the secondary symptoms of migraine such as nausea, photophobia, phonophobia and functional disability.11
Fig 2.0 Percentage of patient with reduced pain levels on the Mantel-Haenszel test by the treatment group versus placebo. (*p≤0.05)
Efficacy and Safety of Triptans
The second evidence that is evaluated relates to the efficacy of triptans in the treatment of migraine. The triptan drug evaluated is sumatriptan which is one of the most common triptan baseddrugs. The study was conducted by Winner, Rothner, Saper et al., and published in volume 106, issue 5 of the Journal Pediatrics under the title “A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents.”14 The study objectives were to determine the comparative efficiency and tolerability of sumatriptan nasal spray, 5mg, 10mg and 20mg in the treatment of acute migraines in adolescents aged 12 to 17 years.
Study Design
The study was a placebo controlled, randomized, double blind, single attack study in which adolescents with a history of migraine were recruited and given different doses of sumatriptan nasal spray or placebo and then observed to determine efficacy.
Inclusion and Exclusion criteria
The inclusion criteria for the study were adolescent participants aged 12 to 17 years with a 6 month history of migraine. The participants had to meet the International Headache Society Criteria 1.1 (with aura) and 1.2 (without aura) for migraine. In addition, the participants had 2 to 8 moderate to severe attacks of migraine in the two months preceding the study and below 15 tension headaches per month. The participants had also failed at least one over the counter or prescription treatment of migraine.
Those with a history of congenital heart disease, cardiovascular disease, prinzmental angina, Kawasaki disease, cardiac arrhythmia, systemic lupus erythematosus, renal and hepatic complication, cerebrovascular pathologies and use of drugs and alcohol were excluded from the study.14 In addition; female participants were excluded if they were pregnant, breast feeding or were sexually active and used no reliable contraceptive.
Sampling, Randomization and group interventions
653 participants were recruited for the study in 46 sites in the US. Figure 3.0 shows the profile of the study. The participants were trained in the use of NS device and patient diaries and were contracted by the investigators every two weeks because of follow up on some inclusion criteria such as use of contraceptives. The participants were randomly allocated to groups that received a single dose of sumatriptan (5mg, 10mg or 20mg) or placebo NS.14 The participants self administered the therapy at home. The efficacy measure was headache relief 2 hours after application of therapy. Safety of sumatriptan and its tolerability were assessed through ECG, vital sighs, physical examinations and clinical laboratory tests. 14
Fig 3.0 Profile of the Study
Research Findings and Interpretation
Participants using 10mg and 20 mg of sumatriptan had the significantly greater headache relief levels at 56% each compared to 41% for those on placebo. Two hours after therapy application, 66% of participants on 5mg sumatriptan had headache relief compared to 53% of placebo. Sumatriptan doses were statistically superior to placebo based on cumulative percentages in 2 hours. Figure 4.0 shows the probability of headache relief in 2 hours of taking a therapy based on Kaplan-Meier survival analysis. Sumatriptan participants had better outcomes in terms of alleviation of symptoms of migraine and had no detectable serious adverse effect. This demonstrates that sumatriptan is safe, tolerable and effective for use in treating migraine in adolescents.
Fig 4.0 Estimated probabilities of headache relief within 2 hours of therapy based on Kaplan-Meier survival analysis
Conclusion
Migraines affect a substantial part of the population. Pharmacologic management of migraine is based on triptans and NSAIDs. From the evaluated evidence, both triptans and NSAIDs have high efficacy for the management of migraine pains. In addition, triptans alleviate other symptoms of migraine hence its higher efficacy. The evaluated evidence is drawn from randomized controlled trials which is the research design of choice when conducting clinical trials and the comparison of the efficacy of various drugs. The evaluated evidence has scientific rigor due to the use of suitable research designs, and suitable data analysis. From the evaluated evidence, the use of triptans and NSAIDs is recommended in the clinical management of migraine headache within the limitations of the study. The most significant limitation is that since both studies excluded pregnant women and nursing mothers, the findings should not be used as evidence for the use of triptans and NSAIDs by these women.
References
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- Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ (Clinical research ed.) 2009 Oct 339: b3914
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- Tepper SJ, Rapoport AM, Sheftell FD. Mechanisms of action of the 5-HT1B/1D receptor agonists Archives of neurology 2002 59 (7): 1084–1088.
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- Derry S, Rabbie R, Moore RA. Diclofenac with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2010 2: CD008783.
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