Key result
Initiation of SNRIs or other antidepressants was not associated with an increased risk of serious liver injury compared with SSRIs (e.g., venlafaxine HR 1.17).
Why the study?
Does the initiation of SNRIs or other antidepressants increase the risk of serious liver injury compared to SSRIs in adults?
Cohort (n=4,966,825)
Does the initiation of SNRIs or other antidepressants increase the risk of serious liver injury compared to SSRIs in adults?
In a large real-world cohort of nearly 5 million individuals, initiation of SNRIs or other atypical antidepressants was not associated with a higher risk of serious liver injury compared to SSRIs.
Answers are grounded in this paper and cite their sources.
No elevated serious liver injury risk with SNRIs or other antidepressants versus SSRIs; supports comparable hepatic safety but leaves open need for prospective confirmation.
BACKGROUND: Hepatotoxicity may be a concern when prescribing antidepressants. Nevertheless, this risk remains poorly understood for serotonin and noradrenaline reuptake inhibitors (SNRIs: venlafaxine, milnacipran, duloxetine) and 'other antidepressants' (mianserin, mirtazapine, tianeptine and agomelatine), particularly in comparison with selective serotonin reuptake inhibitors (SSRIs: fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram), which are by far the most commonly prescribed antidepressants. OBJECTIVE: We quantified the risk of serious liver injury associated with new use of SNRIs and 'other antidepressants' compared with SSRIs in real-life practice. METHODS: Based on the French national health insurance database, this cohort study included 4,966,825 individuals aged 25 years and older with a first reimbursement of SSRIs, SNRIs or 'other antidepressants' between January 2010 and June 2015. We compared the risk of serious liver injury within the 6 months following antidepressant initiation according to antidepressant class, with SSRIs as the reference, using an inverse probability-of-treatment-weighted Cox proportional hazard model adjusted for demographic characteristics and risk factors of liver injury. RESULTS: We identified 382 serious liver injuries overall (none for milnacipran initiators). Age and gender standardized incidence rates per 100,000 person-years were 19.2 for SSRIs, 22.2 for venlafaxine, 12.6 for duloxetine, 21.5 for mianserin, 32.8 for mirtazapine, 31.6 for tianeptine and 24.6 for agomelatine initiators. Initiation of antidepressants of interest versus SSRIs was not associated with an increased risk of serious liver injury [adjusted hazard ratios (95% confidence interval): venlafaxine 1.17 (0.83-1.64), duloxetine 0.54 (0.28-1.02), mianserin 0.90 (0.58-1.41), mirtazapine 1.17 (0.67-2.02), tianeptine 1.35 (0.82-2.23) and agomelatine 1.07 (0.51-2.23)]. This finding was confirmed by the results of an additional study using a case-time-control design. CONCLUSION: These results do not provide evidence of an increased risk of serious liver injury following initiation of SNRIs or 'other antidepressants' compared with SSRIs in real-life practice. This could reflect an inherent lack of difference in risk between the drug classes, or the fact that individuals with higher susceptibility to drug-induced liver injury are not prescribed drugs considered to be more hepatotoxic.
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Gage et al. (2018) conducted a cohort in Antidepressant initiation (n=4,966,825). SNRIs and other antidepressants (e.g., venlafaxine) vs. Selective serotonin reuptake inhibitors (SSRIs) was evaluated on Serious liver injury resulting in hospitalization within 6 months (HR 1.17, 95% CI 0.83-1.64, p=0.36). Initiation of SNRIs or other antidepressants was not associated with an increased risk of serious liver injury compared with SSRIs (e.g., venlafaxine HR 1.17).
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