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Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect.
- Source :
-
British journal of clinical pharmacology [Br J Clin Pharmacol] 2019 Nov; Vol. 85 (11), pp. 2487-2498. Date of Electronic Publication: 2019 Sep 04. - Publication Year :
- 2019
-
Abstract
- In randomised controlled trials (RCTs) of oral drug treatment of migraine attacks, efficacy is evaluated after 2 hours. The effect of oral naratriptan 2.5 mg with a maximum blood concentration (T <subscript>max</subscript> ) at 2 hours increases from 2 to 4 hours in RCTs. To check whether such a delayed effect is also present for other oral antimigraine drugs, we hand-searched the literature for publications on RCTs reporting efficacy. Two triptans, 3 nonsteroidal anti-inflammatory drugs (NSAIDs), a triptan combined with an NSAID and a calcitonin gene-related peptide receptor antagonist were evaluated for their therapeutic gain with determination of time to maximum effect (E <subscript>max</subscript> ). E <subscript>max</subscript> was compared with known T <subscript>max</subscript> from pharmacokinetic studies to estimate the delay to pain-free. The delay in therapeutic gain varied from 1-2 hours for zolmitriptan 5 mg to 7 hours for naproxen 500 mg. An increase in effect from 2 to 4 hours was observed after eletriptan 40 mg, frovatriptan 2.5 mg and lasmiditan 200 mg, and after rizatriptan 10 mg (T <subscript>max</subscript>  = 1 h) from 1 to 2 hours. This strongly indicates a general delay of effect in oral antimigraine drugs. A review of 5 possible effects of triptans on the trigemino-vascular system did not yield a simple explanation for the delay. In addition, E <subscript>max</subscript> for triptans probably depends partly on the rise in plasma levels and not only on its maximum. The most likely explanation for the delay in effect is that a complex antimigraine system with more than 1 site of action is involved.<br /> (© 2019 The British Pharmacological Society.)
- Subjects :
- Administration, Oral
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Arteries drug effects
Arteries innervation
Calcitonin Gene-Related Peptide Receptor Antagonists administration & dosage
Humans
Migraine Disorders physiopathology
Nociception drug effects
Nociception physiology
Serotonin 5-HT1 Receptor Agonists administration & dosage
Thalamus drug effects
Thalamus physiopathology
Time Factors
Treatment Outcome
Trigeminal Ganglion drug effects
Trigeminal Ganglion physiopathology
Vasoconstriction drug effects
Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics
Calcitonin Gene-Related Peptide Receptor Antagonists pharmacokinetics
Migraine Disorders drug therapy
Randomized Controlled Trials as Topic
Serotonin 5-HT1 Receptor Agonists pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2125
- Volume :
- 85
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- British journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31389059
- Full Text :
- https://doi.org/10.1111/bcp.14090