Antidepressants in Dialysis Patients- Part 1

Antidepressants in Dialysis Patients- Part 1

 

Part 1 will focus on SSRIs, SNRIs, NDRIs, NaSSAs, NRI & Serotonin Modulators. 

 

1. SSRIs (Selective Serotonin Reuptake Inhibitors)

 

SSRI Dosage Adjustment Recommendations in Dialysis
Fluoxetine
    • Not removed by hemodialysis

 

    • Fluoxetine administered as 20 mg once daily for 2 months produced steady-state fluoxetine and norfluoxetine plasma concentrations comparable with those seen in patients with normal renal function.

 

  • Recommendation: Use of lower dose or less frequent dosing is NOT usually necessary.
Paroxetine
    • CrCl <30 mL/min: Plasma concentration is ~4 times compared to patient with normal kidney function.

 

  • Recommendation: Initial dose is 10 mg/day. Increases dose at longer intervals. Max dose: 40 mg/day.
Fluvoxamine
    • CrCl 5-45 mL/min: Plasma concentrations after 4 weeks and 6 weeks of treatment (50 mg given twice daily) were comparable to each other, suggesting no accumulation of fluvoxamine in these patients.

 

  • Recommendation: No dosage adjustment necessary.
Sertraline
    • Pharmacokinetics and protein binding are unaffected by renal disease.

 

    • Recommendation (per package insert): No dosage adjustment necessary.

 

  • According to European Renal Best Practice: in Dialysis patient start at 25 mg daily and consider reducing max dose.
Citalopram
    • No information is available about the pharmacokinetics of citalopram in patients with severely reduced renal function (creatinine clearance < 20 mL/min).

 

    • Study by Spigset et al: Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. They recommends that severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary.

 

  • Recommendation (per package insert): Use Caution.
Escitalopram
  • No information is available about the pharmacokinetics of escitalopram in patients with severely reduced renal function (creatinine clearance < 20 mL/min)
  • Recommendation: Use Caution.
  • According to European Renal Best Practice: in Dialysis patient initiate at 10 mg and increase carefully.

 

Based on above information Fluoxetine and Fluvoxamine are safer option for dialysis patients followed by Sertraline.

 

2. SNRI (Serotonin Norepinephrin Reuptake Inhibitor)

 

SNRI Dosage Adjustment Recommendations in Dialysis
Venelafaxine
  • With GFR of 10-70 mL/min: elimination half-life after oral administration was prolonged by about 50% and clearance was reduced by about 24%
  • In dialysis patients: elimination half-life was prolonged by about 180% and clearance was reduced by about 57%.
  • Recommendations (per package insert): Total daily dose be reduced by 50% in patients undergoing hemodialysis.
  • According to European Renal Best Practice37.5–112.5 mg
Duloxetine
    • Increased plasma concentration of CYMBALTA, and especially of its metabolites, occur in patients with end-stage renal disease.

 

    • Recommendations (per package insert): Avoid use in patients with severe renal impairment, GFR <30 mL/min.

 

  • According to European Renal Best Practice: Initiate at 40 mg and increase carefully.
Desvenlafaxine
  • The recommended dose in patients with severe renal impairment and end-stage renal disease (ESRD) is 50 mg every other day and the dose should not be escalated.

 

Based on above information SNRIs needs dose reductions in dialysis and are not first line antidepressants, compared to SSRIs above.

 

3. NDRI (Norepinephrine dopamine re-uptake inhibitor)

 

NDRI Dosage Adjustment Recommendations in Dialysis
Bupropion
  • Recommendations: use with caution in patients with renal impairment and a reduced frequency and/or dose should be considered as bupropion and its metabolites may accumulate in such patients to a greater extent than usual.
  • According to European Renal Best Practice: 150 mg daily

 

 

4. NaSSAs (Noradrenergics and Specific Serotonergics)

 

NaSSAs Dosage Adjustment Recommendations in Dialysis
 Mirtazapine
    • CrCl 11-40 ml/min: Total body clearance reduced by ~ 30%

 

    • Clcr < 10 mL/min: Total body clearance reduced by ~  50%

 

    • Recommendations: Use with caution

 

  • According to European Renal Best Practice: 15 mg and increase carefully.

 

 

5. Serotonin Modulators

 

Serotonin Modulators Dosage Adjustment Recommendations in Dialysis
Trazodone
    • Not been studied in patients with renal impairment.

 

    • Recommendations: used with caution in this population.

 

    • According to European Renal Best Practice:

 

  • 150 mg and increase carefully.
Nefazodone
    • In studies involving 29 renally impaired patients, renal impairment (creatinine clearances ranging from 7 to 60 mL/min) had no effect on steady-state nefazodone plasma concentrations.

 

    • RecommendationsNo dosage adjustment necessary.

 

  • According to European Renal Best Practice: 100 mg and increase carefully.

 

Based on above information Nefazodone should be preferred over Trazodone in dialysis patients.

 

6. NRI (Selective Norepinephrine Reuptake Inhibitor)

 

NRI Dosage Adjustment Recommendations in Dialysis
Reboxetine
    • An increase in systemic exposure and t1/2 up to threefold was observed in patients (n=6) with severe renal insufficiency (creatinine clearance = 10 to 20 mL/min) following a 4 mg oral dose of reboxetine.

 

  • Recommendations: Initiate at 2 mg twice daily and slow titration

 

Information on TCAs and MAOIs will be posted in PART-2 of this post.

 

References:

  1. Package Insert for: Fluoxetine, Paroxetine, Fluvoxamine, Sertraline, Citalopram, Escitalopram, Venelafaxine, DuloxetineDesvenlafaxine, Bupropion, Mirtazapine, Trazodone, Nefazodone, Reboxetine.
  2. Spigset et al. Eur J Clin Pharmacol. 2000 Dec;56(9-10):699-703.
  3. European Renal Best Practice. Nephrol Dial Transplant. 2012 Oct;27(10):3736-45.

 

 

Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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