Table 2.
Antidepressants and liver toxicity
| Epidemiology | Type of lesion | Mechanism | |
| Tricyclic antidepressants | |||
| Imipramine | ALT transient elevation-20%[45] Cholestatic jaundice: 0.5%-1%[2] DILI: 4/100000 patient-years[2,46] Fatal/Trxp DILI: 1[47] | Hepatocellular, cholestatic | Immuno-allergic |
| Amitriptiline | ALT transient elevation-10%[45] Abnormal LFT: 3%[48] Fatal/Trxp DILI: 1[39] | Hepatocellular, cholestatic | Immuno-allergic |
| Clomipramine | Severe DILI: 2 reports[42,49] | Hepatocellular | Immuno-allergic |
| MAO inibitors | |||
| Moclobemide | Abnormal LFT: 3%[50] Fatal DILI: 1[51] | Hepatocellular, cholestatic | Immuno-allergic |
| Serotonin-norepinephrine reuptake inhibitors | |||
| Venlafaxine | ALT > 3ULN: 0.4%[52] Severe DILI: 6[53-56] Fatal DILI/Trxp: 1[57] | Hepatocellular, cholestatic | Immuno-allergic, metabolic |
| Duloxetine | ALT > 3ULN: 1.1%[58] ALT > 5ULN: 0.6%[59] DILI: 26.2/100000 patient-years[60,61] Severe DILI-7[5] Fatal/Trxp DILI: 13[60] | Hepatocellular, cholestatic, mixed | Immuno-allergic, metabolic |
| Serotonin-reuptake inhibitors | |||
| Sertraline | ALT > 3ULN: 0.5%-1.3%[46] DILI: 1.28/100000 patient-years[46] Severe DILI: 4[62-65] Fatal/Trxp DILI: 2[66,67] | Hepatocellular, cholestatic, mixed | Immuno-allergic, metabolic |
| Paroxetine | ALT > 3ULN: 1%[46] Severe DILI: 4[68-71] | Hepatocellular, cholestatic, chronic hepatitis | Metabolic |
| Fluoxetine | ALT > 3ULN: 0.5%[46] Severe DILI: 6[72-77] | Hepatocellular, cholestatic, chronic hepatitis | Metabolic |
| Fluvoxamine | Unknown[38] DILI: 3[78-80] | Hepatocellular | Metabolic |
| Citalopram, escitalopram | No difference in LFT vs placebo[81,82] | ? | ? |
| Other antidepressants | |||
| Nefazodone | DILI: 28.96/10000 patient-years[38] Severe DILI-35[83] Fatal-20[83] | Hepatocellular, cholestatic, mixed | Metabolic |
| Trazodone | ALT > 3 unknown[38] Severe DILI-7[84] Fatal/Trxp DILI-2[57,85] | Hepatocellular, cholestatic | Immuno-allergic |
| Bupropion | ALT > 3ULN: 0.1%-1%[86] Severe DILI: 3[86-88] Fatal/Trxp DILI: 2[89,90] | ? | ? |
| Agomelatine | ALT > 3ULN: 1.4% (25 mg/d) ALT > 3ULN: 2.5% (50 mg/d)[6,91] Severe DILI: 6 reports[92,93] Fatal/Trxp DILI: 1[94] | Hepatocellular | |
| Mirtazapine | ALT > 3ULN: 2%[95] Severe DILI 2: reports[96] | ||
DILI: Drug-induced liver injury; ALT: Alanine aminotransferase; LFT: Liver function tests; ULN: Upper normal limit.