title: Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants.
abstract: BACKGROUND
  Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant.
  
  
  METHODS
  This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed.
  
  
  CONCLUSIONS
  The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.
authors.affiliation: University of Messina, Department of Clinical and Experimental Medicine , Messina , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Italiano
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004790:Enzyme Induction; D006801:Humans
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents
keywords: antidepressants; antiepileptics; drug interactions; pharmacodynamics; pharmacokinetics