Which antidepressants are contraindicated in patients with Impaired Renal Function (IRF)?

From the Guidelines

In patients with renal failure, antidepressants such as lithium, venlafaxine, desvenlafaxine, duloxetine, and milnacipran are contraindicated or require significant dose adjustments due to the risk of toxicity and adverse effects. The primary concern with these medications is the accumulation of parent compounds or active metabolites, which can lead to serious adverse effects including serotonin syndrome, hypertension, and seizures 1.

Key Considerations

• Lithium is exclusively eliminated by the kidneys and has a narrow therapeutic window, making it particularly problematic in renal failure.
• SNRIs like venlafaxine and duloxetine require cautious use due to the potential accumulation of active metabolites.
• Tricyclic antidepressants (TCAs) such as amitriptyline and nortriptyline should be used with reduced doses to avoid metabolite accumulation.
• SSRIs, including citalopram, escitalopram, and sertraline, are generally safer options and require minimal dose adjustments.
• Mirtazapine and bupropion can be used with appropriate dose reductions.

Safe Alternatives

• SSRIs: citalopram, escitalopram, and sertraline are preferred choices due to their minimal dose adjustment requirements.
• Mirtazapine and bupropion can be used with caution and appropriate dose reductions.

Dosing Considerations

• Reduced doses and careful monitoring are necessary when using antidepressants in patients with renal failure to minimize the risk of toxicity and adverse effects 1.

From the Research

Antidepressants Contraindicated in Renal Failure

• The following antidepressants are associated with adverse effects in patients with end-stage renal disease (ESRD) and should be used with caution or avoided:
  • Tricyclic antidepressants 2
  • Lithium, which is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users 3
• Specific antidepressants that require dose reduction in patients with chronic kidney disease (CKD) stages 3-5 include:
  • Selegiline
  • Amitriptylinoxide
  • Venlafaxine
  • Desvenlafaxine
  • Milnacipran
  • Bupropion
  • Reboxetine
  • Tianeptine 4
• Antidepressants that may be safer to use in patients with CKD include:
  • Selective serotonin reuptake inhibitors (SSRIs) 5, 3, 6
  • Mirtazapine, although it may be associated with a higher hazard of mortality compared to SSRIs 6
• It is essential to carefully monitor patients with CKD who are taking antidepressants and adjust doses as needed to minimize adverse effects 4, 2, 6