Savvy Psychopharmacology

When to adjust the dosing of psychotropics in patients with renal impairment

Current Psychiatry. 2016 August;15(8):60-66

References

1. Levy G. Pharmacokinetics in renal disease. Am J Med. 1977;62(4):461-465.
2. Preskorn SH. Clinically important differences in the pharmacokinetics of the ten newer “atypical” antipsychotics: part 3. Effects of renal and hepatic impairment. J Psychiatr Pract. 2012;18(6):430-437.
3. Cohen LM, Tessier EG, Germain MJ, et al. Update on psychotropic medication use in renal disease. Psychosomatics. 2004;45(1):34-48.
4. Baghdady NT, Banik S, Swartz SA, et al. Psychotropic drugs and renal failure: translating the evidence for clinical practice. Adv Ther. 2009;26(4):404-424.
5. Sheehan J, White A, Wilson R. Hazards of phenothiazines in chronic renal failure. Ir Med J. 1982;75(9):335.
6. Haloperidol [monograph]. In: Micromedex Drugdex [online database]. Greenwood Village, CO: Truven Health Analytics. Accessed December 17, 2014.
7. Sheehan JJ, Sliwa JK, Amatniek JC, et al. Atypical antipsychotic metabolism and excretion. Curr Drug Metab. 2010;11(6):516-525.
8. Clozaril [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2014.
9. Risperdal [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2014.
10. Invega [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2014.
11. Latuda [package insert]. Fort Lee, NJ: Sunovion Pharmaceuticals; 2013.
12. Aweeka F, Jayesekara D, Horton M, et al. The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function. Br J Clin Pharmacol. 2004;49(suppl 1):27S-33S.
13. Peeters P, Bockbrader H, Spaans E, et al. Asenapine pharmacokinetics in hepatic and renal impairment. Clin Pharmacol. 2011;50(7):471-481.
14. Mallikaarjun S, Shoaf SE, Boulton DW, et al. Effects of hepatic or renal impairment on the pharmacokinetics of aripiprazole. Clin Pharmacokinet. 2008;47(8):533-542.
15. Thyrum PT, Wong YW, Yeh C. Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment. Prog Neuropsychopharmacol Biol Psychiatry. 2000;24(4):521-533.
16. Lexi-Drugs. Lexicomp. Hudson, OH: Wolters Kluwer Health, Inc. http://online.lexi.com. Accessed May 28, 2015.
17. Lexapro [package insert]. Forest Pharmaceuticals, Inc.: St. Louis, MO; 2014.
18. Celexa [package insert]. Forest Pharmaceuticals, Inc.: St. Louis, MO; 2014.
19. Paxil [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2008.
20. Effexor [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2010.
21. Pristiq [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2014.
22. Cymbalta [package insert]. Indianapolis, IN: Lilly USA, LLC; 2014.
23. Savella [package insert]. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2013.
24. Fetzima [package insert]. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2014.
25. Kurella M, Bennett WM, Chertow GM. Analgesia in patients with ESRD: a review of available evidence. Am J Kidney Dis. 2003;42(2):217-228.
26. Wellbutrin [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2014.
27. Worrall SP, Almond MK, Dhillon S. Pharmacokinetics of bupropion and its metabolites in haemodialysis patients who smoke. A single dose study. Nephron Clin Pract. 2004;97(3):c83-c89.
28. Nagler EV, Webster AC, Vanholder R, et al. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2012;27(10):3736-3745.
29. Norpramin. [package insert] Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2014.
30. Tofranil [package insert]. Hazelwood, MO: Mallinckrodt Inc.; 2014.
31. Pamelor [package insert]. Hazelwood, MO: Mallinckrodt Inc.; 2014.
32. Marplan [package insert]. Parsippany, NJ: Validus Pharmaceuticals, LLC; 2012.
33. Nardil [package insert]. New York, NY: Parke-Davis Division of Pfizer Inc.; 2009.
34. EMSAM [package insert]. Morgantown, WV: Mylan Specialty, L.P.; 2014.
35. Eldepryl [package insert]. Morgantown, WV: Somerset Pharmaceuticals, Inc.; 2009.
36. Parnate [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2008.
37. Culpepper L. Reducing the burden of difficult-to-treat major depressive disorder: revisiting monoamine oxidase inhibitor therapy. Prim Care Companion CNS Disord. 2013;15(5). doi: 10.4088/PCC.13r01515.
38. Tossani E, Cassano P, Fava M. Depression and renal disease. Semin Dial. 2005;18(2):73-81.
39. Young AH, Hammond JM. Lithium in mood disorders: increasing evidence base, declining use? Br J Psychiatry. 2007;191:474-476.
40. Eskalith [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2003.
41. Rej S, Looper K, Segal M. The effect of serum lithium levels on renal function in geriatric outpatients: a retrospective longitudinal study. Drugs Aging. 2013;30(6):409-415.
42. Malhi GS, Tanious M, Das P, et al. The science and practice of lithium therapy. Aust N Z J Psychiatry. 2012;46(3):192-211.
43. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2014.
44. Kaufman KR. Lamotrigine and hemodialysis in bipolar disorder: case analysis of dosing strategy with literature review. Bipolar Disord. 2010;12(4):446-449.
45. Trileptal [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2014.
46. Rouan MC, Lecaillon JB, Godbillon J, et al. The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites. Eur J Clin Pharmacol. 1994;47(2):161-167.

Lamotrigine and its main glucuronidated metabolite, lamotrigine-2N-glucuronide (L-2-N-G), are primarily excreted renally. In severe renal impairment and ESRD, the L-2-N-G levels are elevated but are not pharmacologically active and, therefore, do not affect plasma concentration or efficacy of lamotrigine.⁴³ Although data are limited regarding the use of lamotrigine in severe renal impairment and ESRD, Kaufman⁴⁴ reported a 17% to 20% decrease in concentration after dialysis—suggesting that post-dialysis titration might be needed in these patients.

Oxcarbazepine is metabolized by means of cytosolic enzymes in the liver to its primary pharmacologically active metabolite, 10-monohydroxy, which is further metabolized via glucuronidation and then renally excreted. There are no dosage adjustment recommendations for patients with an eCrCl >30 mL/min.⁴⁵ Rouan et al⁴⁶ suggest initiating oxcarbazepine at 50% of the recommended dosage and following a longer titration schedule in patients with an eCrCl 10 to 30 mL/min. No dosing suggestions for severe renal impairment and ESRD were provided because of study limitations; however, the general recommendation for psychotropic agents in patients in a severe stage of renal impairment is dosage reduction with close monitoring.⁴⁶

Table 3^41,44,46 summarizes dosage adjustments for mood stabilizers in patients with renal impairment.

Related Resources

Cohen LM, Tessier EG, Germain MJ, et al. Update on psychotropic medication use in renal disease. Psychosomatics. 2004;45(1):34-48.
Baghdady NT, Banik S, Swartz SA, et al. Psychotropic drugs and renal failure: translating the evidence for clinical practice. Adv Ther. 2009;26(4):404-424.

Drug Brand Names
Aripiprazole • Abilify
Asenapine • Saphris
Bupropion • Wellbutrin
Citalopram • Celexa
Clozapine • Clozaril, Fazaclo
Desipramine • Norpramin
Desvenlafaxine • Pristiq
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Haloperidol • Haldol
Iloperidone • Fanapt
Imipramine • Tofranil
Isocarboxazid • Marplan
Lamotrigine • Lamictal
Levomilnacipran • Fetzima
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Mesoridazine • Serentil
Milnacipran • Savella
Nortriptyline • Pamelor
Olanzapine • Zyprexa
Oxcarbazepine • Trileptal
Paliperidone • Invega
Paroxetine • Paxil
Phenelzine • Nardil
Quetiapine • Seroquel
Risperidone • Risperdal
Selegiline • EMSAM, Eldepryl
Thioridazine • Mellaril
Tranylcypromine • Parnate
Venlafaxine • Effexor, Effexor XR
Ziprasidone • Geodon

Disclosures
The contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. This material is the result of work supported with resources and the use of facilities at the Chillicothe Veterans Affairs Medical Center in Chillicothe, Ohio.

When to adjust the dosing of psychotropics in patients with renal impairment

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