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 Antidepressants^{1-2, 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 Inhibitors^{1-2, 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 Agents^{1-2, 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