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Triptans

Triptans. Efficacy and tolerability Steven Ryan Essex University. Migraine and Headaches. Migraine thought to affect 43% of women and 18% of men in their lifetime (US) This is thought to cost the US economy $20 billion in working hours lost annually (2002)

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Triptans

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  1. Triptans Efficacy and tolerability Steven Ryan Essex University

  2. Migraine and Headaches • Migraine • thought to affect 43% of women and 18% of men in their lifetime (US) • This is thought to cost the US economy $20 billion in working hours lost annually (2002) • Only 50% of patients receive the correct diagnosis and only 23% of those use triptans • 21% of people suffering with headaches manage them with opioids or barbiturates • Migraine is ranked by WHO as the 19th most debilitating disease • Headaches • Thought to affect 10 million people in the UK (1:4 women 1:12 men) • Can be classified as cluster headaches, tension headaches, secondary headaches

  3. Triptans • Triptans are selective serotonin (5-HT1B/1D) receptor agonists • “abortive migraine drugs” that are not painkillers Proposed Mechanism • The exact mechanism of action is still not fully understood • Selective vasoconstrictor of the cranial vasculature that were thought to distend (Graham and Wolff 1938) • It is believed that compression of the common carotid artery reduces pain in migraine attacks. • Inhibit abnormal activation of peripheral nociceptors • Effects on the neurons in the trigeminal nucleus caudalis • Sumatriptan is a hydrophilic drug and cannot pass the blood-brain barrier, zolmitriptan and rizatripton are lyphophilic drugs which can potentially pass through the brain blood barrier but sumatriptan is still more effective

  4. Available Types Approved Triptan Brand Formulation 1992 SumatriptanImitrex, Imigran Injections 1995 SumatriptanImitrex, Imigran Tablets 1997 SumatriptanImitrex, Imigran Nasal spray 1997 ZolmitriptanZomig Tablets 1998 NaratriptanAmerge, Naramig Tablets 1998 RizatriptanMaxalt, Maxalt-MLT Tablets 2001 ZolmitriptanZomig-ZMT Dissolvable tablets 2001 AlmotriptanAxert Tablets 2001 FrovatriptanFrova Tablets 2002 EletriptanRelpax Tablets 2003 ZolmitriptanZomig Nasal spray (Adapted from Cologno et al 2012)

  5. End-points and terminology • 30 minutes – pain relief and pain free • 1 hour – pain relief and pain free • 2 hour – pain relief and pain free • Recurrence – 24/48 hours • Adverse events – Relative risks RR • NNT – Numbers needed to treat. eg 5:1, for every 5 patients there was a treatment benefit for 1 • Recurrence is limited - in order to have recurrence a drug has to remove the pain

  6. Pascual J et al 2007 – Systematic Review • Reviewed studies only using oral triptans • Inclusion criteria • Double-blinded RCTs • Placebo arm • Detailed and repeatable literature search procedure provided • Hand search of reference lists • 225 studies were refined to 35. • Studies showed that 6 out of seven triptans were superior to placebo after 2 hours (except naratriptan) • Sumatriptan 50 almotriptan 12.5 and frivotriptan 2.5 were no different than placebo at 1 hour • Almotriptan was the only triptan to have an effect after 1 hour. • The forms of triptan that proved most effective (sumatriptan 100, almotriptan 12.5) had the highest volume of adverse effects • Adverse effects include nausea, vomiting, dizzyness, vertigo, parasthesia • Review funded by GSK Spain and all authors are funded to lecture by pharmaceutical company

  7. Pascual et al.. • Review not clear on specific effects of each type of triptan • Provides a table but neglects to explain the table with a legend or adequate headings • Not explained in text either • ….GO TO PASCUAL PAPER

  8. Adelman JU & Belsey J (2003) • Sumatriptan 50 mg • 602 patients -24% pain free • 5.4 NNT • Sumatriptan 100 mg • 1837 patients - 30% pain free • 4.7 NNT • Rizatriptan 10 mg • 2073 patients – 40% pain free • 3.2 NNT • Zolmitriptan 2.5mg • 727 patients – 29% pain free • 5.1 NNT • Zolmitriptan 5 mg • 936 patients – 31% pain free • 4.2 NNT • Naratriptan 2.5 mg • 213 patients – 20% pain free • 8.2 NNT • Almotriptan 12.5 mg • 730 patients 36% pain free • 4.7 NNT • Frovatriptan 2.5 mg • 1611 patients – 11% pain free • 11.3 NNT • WITHIN 2 Hours

  9. Cost effectiveness of Triptans in 2003 (US) Adapted from Adelman JU & Belsey J (2003) First column: price in dollars for one tablet/dose (2003) Second Column: Available packages at the time Third Column: Price for effective treatment based on NNT (calculated from previous slide) Fourth column: Cost based on two commissioning groups 2012

  10. Johnston MM & Rapoport AM (2010) Review of Literature • Review looking at more recent research • No detail given about literature searching • No detail about specific effects • Sumatriptan • 100 mg had a 5:1 NNT for a painfree response in 2 hours. • recurrence at 24 hours was the same as placebo • High instance of adverse events • 25 mg had a 7.5:1 NNT pain free at 2 hours and 3.5:1 for any significant improvement • Nasal spray is better tolerated with less adverse events. • Higher doses of sumatriptan are more effective but can cause higher risk of adverse events • Zolmitriptan has a 50% higher half life than sulmatriptan but not as effective • Eletriptan has a NNT of 7:1 at 2 hours and 5:1 at 4 hours • Rizatriptan designed to be faster acting • Naratriptan is slower acting, less effective but more tolerable

  11. Frovatriptan and menstrual migraine • 50% of women with migraine associate it with the menstrual cycle • Menstrual migraines are reported as being more severe, disabling, and longer lasting than other migraine. • Frovatriptan designed as a preventative migraine medication with a long lasting effect and a low risk of adverse events. • The pooled results of 3 RCTs assessed 346 women with migraine (187 classified as menstrual) • Frovatriptan found to be no different to three other triptans (almotriptan, rizatriptan and zolmatriptan) for immediate effect but had a lower rate of recurrence after 24 hours • Lower adverse events are found in Frovatription

  12. References • Ahn AH and Basbaum AI (2005) ‘Where do triptans act in the treatment of migraine?” Pain 115(1-2): 1–4. • Adelman A & Belsey J (2003) ‘Meta-analysis of Oral Triptan Therapy for Migraine: Number Needed to Treat and Relative Cost to Achieve Relief Within 2 Hours’ Journal of Managed Care Pharmacology (9)1: 45-52 • Allais VincenzoTullo Stefano OmboniChiaraBenedettoGraziaSances Dario Zava Michel D. Ferrari GennaroBussone (2012) Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies Neuroscience 33(1) 565-569 • Cologno D Mazzeo A Lecce B Mundi C Petretta V Casucci G d’Onofrio F (2012) ‘Triptans: over the migraine’ Neuroscience 33(1) 193-198 • Johnston MM & Rapoport AM (2010) ”Triptans for the Management of Migraine’ Drugs 70 (12); 1505-1616 • National Health Service (2013) Headaches • Pascual J Mateos V Roig Sanchez-del-Rio M Jimenez D (2007) ‘Marketed Oral Triptans in the Acute Treatment of Migraine: A Systematic Review on Efficacy and Tolerability’ Headache 47:1152-1168 • NHS Corby Clinical Commissioning group (2012) http://www.neneccg.nhs.uk/resources/uploads/files/Triptan%20comparison.pdf

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