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Table 2 Evidence for antidepressant treatment of depression during HCV Therapy and drug interactions with DAAs

From: Psychiatric treatment considerations with direct acting antivirals in hepatitis C

Level of evidence for depression treatment Antidepressant (route of metabolism) Known or potential interactions with DAAs Comments
Level 1 Escitalopram (CYP2C19, 3A4 >> 2D6) No interaction observed with boceprevir [37] 35% ↓ escitalopram AUC with telaprevir [38] Boceprevir: no dose adjustment required. Telaprevir: May need to titrate escitalopram dose according to clinical response.
Level 2 Citalopram (CYP2C19, 3A4 >> 2D6) Potential for ↓ antidepressant concentrations based on escitalopram interaction data. Monitor and titrate dose according to clinical response.
Paroxetine* (CYP2D6) No interaction expected based on known pharmacologic characteristics. Monitor and titrate dose according to clinical response.
Level 4 Bupropion (CYP2B6), Fluoxetine (CYP2D6) No interaction expected based on known pharmacologic characteristics. Monitor and titrate dose according to clinical response.
  Sertraline (CYP2B6 > 2C9/19, 3A4, 2D6, UGT1A1 - possible), Mirtazapine (CYP2D6, 1A2, 3A4), Venlafaxine (CYP2D6 > CYP3A4) Potential for ↑ sertraline, mirtazapine, venlafaxine concentrations (clinical significance unknown). Use with caution; monitor and titrate dose according to clinical response.
Desvenlafaxine (UGT>>3A4) [39, 40] Potential for ↑ desvenlafaxine concentrations (clinical significance unknown). Monitor and titrate antidepressant dose according to clinical response.
Tricyclic antidepressants i.e. Desipramine (CYP2D6>>UGT), Imipramine (CYP2D6, 1A2, 2C19, 3A > UGT), Trazodone** (CYP2D6> CYP3A) Potential increase in TCA concentrations resulting in dizziness, hypotension and syncope. Use with caution with DAAs, lower TCA doses are recommended.
Nortriptyline (CYP2D6) No interaction expected based on known pharmacologic characteristics. Monitor and titrate dose according to clinical response.
Avoid (exceptional circumstances only) Duloxetine (CYP1A2, 2D6) Duloxetine: risk of hepatotoxicity. Duloxetine is contraindicated in liver disease.
Nefazodone (CYP3A4) Nefazodone: potential for ↑ nefazodone and/or DAA concentrations; also risk of hepatotoxicity. Nefazone was discontinued in the United States and Canada in 2003 due to hepatotoxicity concerns. Avoid use in liver disease.
  St. John’s Wort (hypericum perforatum); induces CYP3A4 and P-gp [40]. Potential for ↓ DAA concentrations. St. John’s Wort is contraindicated with boceprevir [19] and telaprevir [18].
  1. *Evidence in RCT for depressed mood component of major depression only.
  2. **Trazodone is primarily used clinically for treating insomnia.
  3. Level of Evidence: Level I (≥ 2 RCTs or meta-analysis), Level 2 (1 RCT), Level 4 (Case reports/series or expert opinion).