The Pharmacotherapeutics of Migraines - Report Example

The pharmacotherapeutics of migraines Course: Lecturer: Date: Migraine headaches exhibit a neurological disorder causing episodic headaches and other associated symptoms (1). Sensory stimuli and sensitivity to environment are critical factors for migraine headaches. Acute episodes of migraine have different approaches to treatment. NSAIDS fall under nonspecific treatment while Triptans are administered under specific treatment (2). The goal for acute treatment is to reduce the rapid and consistent recurrence. NSAIDs have a long history of use from ancient use of it raw products to the recent example of Aspirin while Triptans have been used over decades from 1990 and there are now the second generation triptans that have turned out to be more useful (3). The formulations and sales of the drugs through physicians’ prescriptions and OTC, evidence to their efficacy in relief of migraine headaches. The first generation triptans have been fast-acting drugs in hindering migraine chemistry and thus halts migraine pain and combat the accompanying symptoms such as light sensitivity, nausea and vomiting. The 7 triptans in the market has established efficacy profile through well controlled trials. However, triptans has a disadvantage since they are of high cost and restricted to be used in presence of cardiovascular diseases. NSAIDs have marginal and moderate side-effects and are of low cost (4). Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for long for lower fever and headache treatment. Since they are anti-inflammatory, they reduce swelling through their mechanism that blocks proteins ad enzymes made by the body. Under non-specific treatment of migraine, NSAIDs provides the PGI2 and PGE2 that reduce the threshold of nociceptors stimulation that causes peripheral sensitization. PGE2 modulate the CGRP released from trigeminal sensory neurons terminals. This blocks cyclooxygenase which further reduces PG synthesis. NSAIDs are efficacious for the relief from associated symptoms and sustained pain (5). Caffeine also combines with NSAIDs to produce metoclopramide that effectively reduce nausea and vomiting that are associated with various headaches. The antagonistic action of D2 is taken as a factor for migraine relieve. Intake of caffeine promotes the vasoconstriction action, hence block the adenosine receptor. The treatment approach with NSAIDs ensures that sensory stimuli are inhabited and thus migraineur part of brain is not sensitive to changes around it. NSAIDs reduce the reactive vasodilatation which activates the primary sensory neurons. Most NSAIDs are used with short-term headaches of migraine disease; however, they are limited for long-term prevention (6). They are however successful with menstrual migraines and those caused by exertion and exercise. Some NSAIDs are OTC drugs which does not need any prescription. However others must be prescribed by a doctor. NSAIDs are often used, but there are various reported mild side-effects such as upset stomach, rash, heartburn and ulcers. However, if they are taken with food, the digestive side effects are reduced and thus it assures safety. In addition, due to often usage, there are various options and formulations of medications to ensure compatibility and particularly if a patient is vomiting or experiencing nausea. The various forms such as tablet, chewable, capsule and liquid make it easy for patient to swallow and further digest medications (7). Triptans are relatively effective prescription that is used for migraines treatment. 2 out of 3 people that take Triptans have been confirmed for pain relieve within two hours (8). This is successfully achieved if medication is taken when the attack surfaces or as early as migraine occurs. Triptans relieves pain and alleviate other migraine symptoms like vomiting and nausea. They halt migraine discomfort through relieve of the narrowing and swelling blood vessels. They are used for treatment of specific acute treatment. They act through selective activities that promote cranial vasoconstriction and modulate the release of neurotransmitter from neuronal terminals (9). During migraine three things happen in the brain; neural activation, CGRP degranulation and hence blood vessel dilation. The Triptans 5-hydroxytrytamine receptor agonists (5HT) inhibit degranulation through the serotonin agonist which further inhibits the vessel dilation. Triptans prevent the release of vasoactive peptides and reduce PPE. It also inhibits abnormal activation of nociceptors peripheral. The 5-HT1D has greater potency in blocking the electrically induced PPE with little or no detectable vascular activity in meningeal arteries (10). Clinical Trial Design Critique of Clinical Trials This is a contrasting critique of the quality of two clinical trials evaluated in the light of the guidelines set by the CONsolidating Standard of Reporting Trials (CONSORT) for reporting randomized controlled trials (11). Schulz says that randomized trials can yield biased results if they lack methodological rigour (12). The two randomised trials include one by Lampl et al that investigated the efficacy and safety of 1, 000mg of effervescent aspirin and one by Silberstein et al on the efficacy and safety of topiramate for the treatment of migraines. The CONSORT guidelines require researchers to give a statement of all the suspects of how the study is set up. They sought to compare the efficacy of 1000 mg effervescent aspirin (eASA) with 50 mg sumatriptan and placebo in an individual. It was designed as a three randomised, placebo-controlled, single dose migraine trial. Pain relief at 2 hours, pain-free at 2 hours and sustained pain free for up to 2 hours were calculated. This study design was good for measuring the levels of efficacy but may not be effective in determining the safety of aspirin. The efficacy and safety of Topiramate study was designed as a randomised, placebo controlled, parallel group multicenter study. This study consisted of 16 weeks of double-blind treatment (13). While the first trial was done on an individual, the second study was a parallel-group. This study for’s design is better for determining safety since it uses a group. It eliminates bias by preventing concomitant preventive migraine treatment and acute headache medication was not to exceed 4 days. On measuring the efficacy of Topiramate 100/day, the dose started as 25mg/day and was increased daily by 25mg/day to the maximum dose of 100mg/day (14). Inclusion and exclusion criteria All the subjects had to be between ages 18 to 65 years. This criterion was successful as young people below 18 years of age tend to experience headaches through routine changes of activities, geographical location which cannot be identified in a pattern. The old above 65 years are also susceptible to many ailments which affect their health and headache might be brought by multiple factors or diseases. The subjects had to have a record of 15 and over days of headaches in a month. Concomitant preventive migraine kind of treatment was not allowed so that the study may deliver precise result on efficacy after treatment was applied. Preventive treatment may have affected the measures of efficacy as its approach is different with that of treatment after headache. Acute headache medication did not exceed 4 days in a week during the period of study. This was meant to ensure safety of treatment and reduce the side effects that are pertinent with acute modes of treatment (13, 14). Sample Size, Randomization, Blinding, Bias In the first case, where topiramate efficacy and safety was being accessed, 328 subjects were provided with efficacy assessment. However, this was a higher not as the intent was to take 306 where topiramate, n=153 and placebo, n=153. Ultimately, discontinuous occurred for 18 subjects due to serious adverse events. Registered nurses were hired for specific performance of randomization, administration of intervention and as sole persons aware of allocation and access to record of the study during the study. The randomization procedure had to divide the patients into intervention group having a structured program that included the designed treatment (15). Some factors as indicated were variable that could have interfered with study results and thus a restricted randomization was taken to achieve the right balance (16). All studies were double blind since the patients nor did the nurse who administered treatment know the group the patients belonged. The nurses were only involved with informing the patients of the trial, assessing the patients’ eligibility and obtained an informed consent. This reduced bias in response and generalization as the patient and the nurse were unaware of who was being studied (17). Reports were made at least after 30 minutes during the study intervention period. Collected information described the various adverse effects that were experienced after treatment. The primary end point was reduction of headache severity within two hours and the secondary end point involved the total duration of feeling nausea, vomiting and photosensitivity (18). Limitations & Interpretation The test of efficacy and safety for 1,000 mg eASA in comparison with 50 mg sumatriptan and placebo had response rates for eASA was of 51.5% (pain relief 2h), 27.1% (pain-free at 2h) and 23.5% (sustained pain free 24h). For sumatriptan it was 46.6%, 29% and 22.2% in all cases. The corresponding for placebo were 33.9 %, 15.1 % and 14.6 % showing a significant difference of (p < 0.001). However the difference between the eASA and sumatriptan were insignificant (13). Safety was not conclusive as it depended on frequency of adverse events that were reported. However, eASA had lower incidence in adverse events than sumatriptan. For treatment of acute migraine, both eASA 1,000 mg and 50mg sumatriptan are effective. eASA can proceed during migraine attacks but triptan can be used later in case there is no response (19). In Topiramate treatment case, the daily dose of 100 mg led to significant improvements when compared with that of placebo for mean monthly migraine. Topiramate was therefore concluding to be safe and well tolerated in subjects having chronic migraine. Topiramate safety and tolerability were consistent compared with those in previous carried clinical trials of the drug (20). References 1. Diener, HC, & Limmroth, V. Medication-overuse headache: a worldwide problem. The Lancet Neurology. 2004;3(8), 475-483. 2. Moloney, MF, & Cranwell-Bruce, LA. Pharmacological management of migraine headaches. The Nurse Practitioner.2010; 35(9), 16-22. 3. Pascual, J., Mateos, V., Roig, C., Sanchez‐del‐Rio, M., & Jiménez, D. Marketed oral triptans in the acute treatment of migraine: a systematic review on efficacy and tolerability. Headache: The Journal of Head and Face Pain.2007; 47(8), 1152-1168. 4. Kurth, T., Gaziano, JM, Cook, NR, Logroscino, G., Diener, HC, & Buring, JE. Migraine and risk of cardiovascular disease in women. JAMA: the journal of the American Medical Association.2006; 296(3), 283-291. 5. Tfelt-Hansen, P., & McEwen, J. Nonsteroidal anti-inflammatory drugs in the acute treatment of migraine. The headaches.2006; 3, 449-457. 6. Diener, HC, & Wang, SJ. Topiramate in migraine prophylaxis. Journal of neurology.2005; 251(8), 943-950. 7. Kurth, T., Slomke, MA, Kase, CS, Cook, NR, Lee, IM, Gaziano, JM, & Buring, JE. Migraine, headache, and the risk of stroke in women a prospective study. Neurology.2005; 64(6), 1020-1026. 8. Mathew, NT. Antiepileptic drugs in migraine prevention. Headache: The Journal of Head and Face Pain.2001; 41(s1), 18-25. 9. Eiland, LS, & Hunt, MO. The use of triptans for pediatric migraines. Pediatric Drugs.2010; 12(6), 379-389. 10. Rocheville, M., Lange, DC, Kumar, U., Patel, SC, Patel, RC, & Patel, YC. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science signaling.2000; 288(5463), 154. 11. Moher, D., Schulz, K., & Altman, D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Medical Research Methodology. (2001); 1(1), 2. 12. Schulz, KF, Chalmers, I., Hayes, RJ, & Altman, DG. Empirical evidence of bias. JAMA: the journal of the American Medical Association. (1995); 273(5), 408-412. 13. Lampl, C., Voelker, M. & Diener, HC. Efficacy and safety of 1,000 mg effervescent aspirin: individual patient data meta-analysis of three trials in migraine headache and migraine accompanying symptoms. Journal of neurology. (2007) 254(6), 705-712. 14. Silberstein, SD, Lipton, RB, Dodick, DW, Freitag, FG, Ramadan, N., Mathew, N., & Hulihan, J. 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. 15. Jadad, AR, Moore, RA., Carroll, D., Jenkinson, C., Reynolds, DJM. Gavaghan, DJ., & McQuay, HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled clinical trials. (1996); 17(1), 1-12. 16. Friedman, BW, Corbo, J., Lipton, RB, Bijur, PE, Esses, D., Solorzano, C., & Gallagher, EJ. A trial of metoclopramide vs. sumatriptan for the emergency department treatment of migraines. Neurology.2005; 64(3), 463-468. 17. Katsarava, Z., Schneeweiss, S., Kurth, T., Kroener, U., Fritsche, G., Eikermann, A. & Limmroth, V. Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology.2004; 62(5), 788-790. 18. Diener, HC, Rahlfs, VW, & Danesch, U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. European neurology.2004; 51(2), 89-97. 19. Silberstein, SD, Olesen, J., Bousser, MG, Diener, HC, Dodick, D, First, M., & Steiner, TJ. The International Classification of Headache Disorders, (ICHD‐II)—revision of criteria for 8.2 Medication‐overuse headache. Cephalalgia.2005; 25(6), 460-465. 20. Wilding, J., Van Gaal, L., Rissanen, A., Vercruysse, F., & Fitchet, M. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. International journal of obesity. (2004); 28(11), 1399-1410. Read More