title: Choosing the safest acute therapy during chronic migraine prophylactic treatment: pharmacokinetic and pharmacodynamic considerations.
abstract: BACKGROUND
  Drugs used in the treatment of migraine have been reported to be highly associated with the occurrence of clinically significant drug-drug interactions (DDIs). Multiple drug therapy regimens are used for migraine treatment, particularly for chronic migraine. In fact, additional pharmacological agents are usually administered during an acute migraine attack in patients chronically treated with the prophylactic therapy. The variety of drugs available for migraine prophylactic and acute treatment, and consequently their pharmacological interactions, might complicate the choice of a safe combination therapy.
  
  
  METHODS
  This study discusses the prophylactic-acute DDIs from a pharmacokinetic and pharmacodynamic perspective, particularly interactions between antiepileptic drugs, tricyclic antidepressants, β-blockers, calcium channel blockers, triptans, nonsteroidal anti-inflammatory drugs and ergot derivatives. The available online tools have been used to evaluate the clinically significant DDIs.
  
  
  CONCLUSIONS
  The interactions between different drugs might be accurately predicted by the huge and detailed knowledge about the molecular pathways involved in pharmacodynamics and pharmacokinetics. Pharmacogenomic research has shed further light onto the mechanisms involved in the inter-individual variation in drug response and DDIs. Based on this knowledge, this paper will provide suggestions to improve the appropriateness of the drug choice in the prescription of preventative and acute migraine medications.
authors.affiliation: a IDI, Istituto Dermopatico dell'Immacolata-IRCCS , Rome , Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.affiliation: b NESMOS Department , Sapienza University of Rome , Rome , Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Borro
authors.affiliation: c Department of Psychiatry , McLean Hospital, Harvard Medical School , Boston , MA , USA.|d Department of Clinical and Molecular Medicine , Sapienza University of Rome , Rome , Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Curto
authors.affiliation: e Advanced Molecular Diagnostics Unit , Sant'Andrea Hospital , Rome , Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Capi
authors.affiliation: d Department of Clinical and Molecular Medicine , Sapienza University of Rome , Rome , Italy.|f Regional Referral Headache Center , Sant'Andrea Hospital , Rome , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Negro
authors.affiliation: e Advanced Molecular Diagnostics Unit , Sant'Andrea Hospital , Rome , Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Cipolla
authors.affiliation: b NESMOS Department , Sapienza University of Rome , Rome , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gentile
authors.affiliation: d Department of Clinical and Molecular Medicine , Sapienza University of Rome , Rome , Italy.|f Regional Referral Headache Center , Sant'Andrea Hospital , Rome , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Martelletti
mesh_terms: D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000627:therapeutic use; D002908:Chronic Disease; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D010597:Pharmacogenetics; D014363:Tryptamines / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D014363:Tryptamines; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6
keywords: Acute treatment; CYP450; chronic migraine; drug-drug interactions; prophylactic treatment