title: Psychiatric treatment considerations with direct acting antivirals in hepatitis C.
abstract: BACKGROUND
  Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications.
  
  
  METHODS
  We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies.
  
  
  RESULTS
  Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John's Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized.
  
  
  CONCLUSIONS
  Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.
authors.affiliation: University Health Network, Program in Medical Psychiatry, Toronto General Hospital, 200 Elizabeth Street 8EN-228, Toronto, ON M5G 2C4, Canada. sanjeev.sockalingam@uhn.ca
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sockalingam
authors.forename: Alice
authors.initials: A
authors.lastname: Tseng
authors.forename: Pierre
authors.initials: P
authors.lastname: Giguere
authors.forename: David
authors.initials: D
authors.lastname: Wong
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000075202:Contraindications; D004347:Drug Interactions; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D055118:Medication Adherence; D001523:Mental Disorders / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009842:Oligopeptides / Q000009:adverse effects; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives; D011619:Psychotropic Drugs / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011619:Psychotropic Drugs; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline