From the FDA Drug Label
Liver Disease As might be predicted from its primary site of metabolism, liver impairment can affect the elimination of sertraline In patients with chronic mild liver impairment (N=10,8 patients with Child-Pugh scores of 5 to 6 and 2 patients with Child-Pugh scores of 7 to 8) who received 50 mg sertraline per day maintained for 21 days, sertraline clearance was reduced, resulting in approximately 3-fold greater exposure compared to age-matched volunteers with no hepatic impairment (N=10) The exposure to desmethylsertraline was approximately 2-fold greater compared to age-matched volunteers with no hepatic impairment. There were no significant differences in plasma protein binding observed between the two groups. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied The results suggest that the use of sertraline in patients with liver disease must be approached with caution. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
The safest SSRI for someone with liver cirrhosis cannot be determined from the provided information, as the effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. However, for patients with mild liver impairment, a lower or less frequent dose of sertraline should be used.
- Key considerations:
- Liver impairment can affect the elimination of sertraline.
- Patients with liver disease should be approached with caution.
- The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied.
- For mild liver impairment, a lower or less frequent dose should be used. 1
From the Research
For patients with liver cirrhosis, citalopram and escitalopram are generally considered the safest SSRI options, as they undergo less hepatic metabolism and typically require minimal dose adjustments in liver disease. When starting treatment, it's advisable to begin with a lower dose - for citalopram, 10mg daily instead of the usual 20mg; for escitalopram, 5mg daily instead of 10mg. Dose increases should be made cautiously, with close monitoring for side effects. Some key points to consider when prescribing SSRIs to patients with liver cirrhosis include:
- Sertraline may be considered as an alternative, though it requires more hepatic processing, as shown in a study from 2
- Fluoxetine and paroxetine should generally be avoided in cirrhosis patients due to their extensive liver metabolism and longer half-lives, which increase the risk of drug accumulation and adverse effects
- Regular liver function monitoring is essential with any antidepressant in cirrhosis patients, as antidepressant-induced liver injury can be idiosyncratic and unpredictable, and is generally unrelated to drug dosage, as noted in 3
- The recommendation for citalopram or escitalopram is based on their pharmacokinetic profiles, as they have simpler metabolic pathways and fewer active metabolites, reducing the burden on the compromised liver and decreasing the risk of drug interactions in patients who are often on multiple medications, as discussed in 4 and 5. It is also worth noting that all antidepressants can induce hepatotoxicity, especially in elderly patients and those with polypharmacy, as mentioned in 6 and 3.