1.3. Renal Impairment

Many antidepressants do not require significant dosage modifications in renal impairment. However, dosage guidelines for select non-SSRI antidepressants in renal impairment are available. Tables 12-15 summarizes dosage modifications and/or restrictions for specific non-SSRI antidepressant medications.

Table 12: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Tetracyclic Antidepressants1-2, 19-20
Drug Name Dosage in Renal Impairment 
Mirtazapine Initiate with the lowest dosage and titrate slowly as renal clearance reduced by approximately 30% in moderate (Creatinine clearance 11-39 ml/min) and 50% in severe (Creatinine clearance less than 10 ml/min) renal impairment
Table 13: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Monoamine Oxidase Inhibitors1-2, 21-23, 25
Drug Name Dosage in Renal Impairment 
Isocarboxazid Contraindicated in severe renal impairment; use cautiously in moderate renal impairment due to potential accumulation of active metabolites
Phenelzine Contraindicated for use in severe renal impairment
Table 14: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Serotonin and Norepinephrine Reuptake Inhibitors 1-2, 26-32
Drug Name Dosage in Renal Impairment 
Desvenlafaxine
  • Moderate renal impairment (CrCl 30-50 ml/min):
    • 50 mg/day
  • Severe renal impairment (CrCl less than 30 ml/min), ESRD:
    • 25 mg once daily or 50 mg every other day
Duloxetine
  • Mild to moderate renal impairment: start with lower dose, titrate gradually
  • Severe renal impairment (GFR less than 30 ml/min)
  • ESRD: avoid use
Levomilnacipran
  • Moderate renal impairment (CrCl 30-59 ml/min):
    • 80 mg/day
  • Severe renal impairment (CrCl 15-29 ml/min):
    • 40 mg/day
  • ESRD:
    • not recommended
Milnacipran
  • Moderate renal impairment (CrCl 30-49 ml/min): use cautiously
  • Severe renal impairment (CrCl 5-29 ml/min): reduce dose by 50% to 25 mg twice daily or -50 mg once daily (based on response and tolerability)
  • ESRD: not recommended
Venlafaxine
  • Mild to moderate renal impairment (CrCl 30-89 ml/min):
    • IR:  reduce total daily dose by 25%
    • ER:  reduce total daily dose by 25% to 50%
  • Severe renal impairment (CrCl less than 30 ml/min) and hemodialysis:
    • reduce total daily dose by 50%
  • Adjust doses based on response and tolerability due to variability in renal clearance

Legend:

  • CrCl = creatinine clearance
  • ESRD = end-stage renal disease
  • ER = extended-release
  • IR = immediate-release 
Table 15: Select non-SSRI Antidepressant Dosage Modifications in Renal Impairment – Other Miscellaneous Agents1-2, 35-38, 40
Drug Name Dosage in Renal Impairment
Bupropion Administer cautiously in renal impairment due to potential for accumulation and risk for adverse events (e.g., seizures); consider reduced dosage/dosage frequency Forfivo™ XL: not recommended in renal impairment as no lower dose available
Trazodone Use cautiously in patients with renal impairment 

Legend:

  • CrCl = creatinine clearance