Table 2.
Evidence for antidepressant treatment of depression during HCV Therapy and drug interactions with DAAs
| 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]. |
*Evidence in RCT for depressed mood component of major depression only.
**Trazodone is primarily used clinically for treating insomnia.
Level of Evidence: Level I (≥ 2 RCTs or meta-analysis), Level 2 (1 RCT), Level 4 (Case reports/series or expert opinion).