Table 5. Pharmacotherapies for management of coexistent psychosomatic comorbidities in patients with alcohol use disorder (AUD).
| Class | Acceptable in hepatic impairment | Generally avoid or notable clinical concerns |
|---|---|---|
| SSRI | Sertraline – generally safe, consider decreased dose with hepatic impairment, large dose range 25–200 mg is useful clinically | Fluoxetine – no absolute contraindication. Reduce dose, as half-life may triple with hepatic impairment, drug-drug and 2D6 interactions |
| Escitalopram (s-enantiomer of citalopram) – do not exceed 10 mg/d due to increased risk of QTc prolongation as concentrations may increase by 50% or more with cirrhosis | Paroxetine – Most frequently associated with liver toxicity. Short half-life requires strict compliance due to withdrawal symptoms of this SSRI | |
| Citalopram – do not exceed 20 mg/d due to increased risk of QTc prolongation, potential for doubling of half-life | Caution or minimize co-administration with antiplatelet or NSAIDs due to increased risk of bleeding | |
| SNRI | Desvenlafaxine (metabolite of venlafaxine) - generally preferable to venlafaxine | Duloxetine – do not use in hepatic impairment, up to 85% reduction in clearance |
| Venlafaxine – no absolute contraindication; dose reduction up to 50% with liver impairment, more so with cirrhosis | ||
| Levomilnacipran – no dose adjustment necessary | ||
| NDRI | Bupropion – generally safe; no significant concerns with CTP A r B class, but consider lowered dose or frequency with CTP class C | Not an absolute contraindication but caution if patient is actively consuming alcohol or with history of withdrawal seizures as it lowers threshold for seizures. Also avoid with history of an eating disorder |
| Antipsychotic | Paliperidone (metabolite of risperidone) – excreted by kidneys, generally safe, no adjustments in CTP A or B, limited data in CTP class C | Risperidone – undergoes hepatic biotransformation; free drug increased up to 35% in CTP class C |
| Olanzapine – generally safe, half-life may be increased, consider starting dose of 2.5 to 5mg and slower titration | ||
| Quetiapine – half-life may be increased but generally safe particularly at lower dosing; start at 25 mg can titrate by 25–50 mg/day | Use haloperidol (first generation) with caution, lower dosing and careful titrations after discussion with pharmacist, generally avoid with active alcohol use | |
| Ziprasidone – no dose adjustment necessary, avoid with prolonged QTc | ||
| Benzodiazepines | Lorazepam, Oxazepam, Temazepam – generally safe but recommend lower dosing | For anxiety or insomnia, prefer hydroxyzine or gabapentin (minimal liver dependence or clearance) due to benzodiazepine addiction potential |
| Other | Trazodone – generally safe; may require dose adjustment based on severity of impairment but minimal data; avoid in hepatic encephalopathy due to sedation | Avoid TCA due to lowered seizure threshold, bleeding risk especially when used with antiplatelet or NSAIDs, confusion and sedation. If used, keep the dose 50% of normal |
| Mirtazapine – generally safe; decreased clearance by up to a third of normal, careful titration | ||
| Vortioxetine – no adjustment for CTP A/B; not studied in CTP C |
AUC, area under the curve; CLD, chronic liver disease; CTP, Child-Turcotte-Pugh; NDRI, norepinephrine-dopamine reuptake inhibitor; NSAID, Nonsteroidal Anti-inflammatory Drugs; QTc, corrected QT interval; TCA, tricyclic antidepressant; QTc, corrected QT interval; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, serotonin-selective reuptake inhibitor.