(128) Bupropion/Hydroxybupropion Therapeutic Drug Monitoring: A Case of Elevated Hydroxybupropion Serum Levels in a Patient with Major Depressive Disorder and Chronic Kidney Disease

Abstract:

Background:
Bupropion is a unique antidepressant medication, acting as a dopamine and norepinephrine reuptake inhibitor, with no direct action on serotonin receptors (Khan, 2015). Bupropion is extensively broken down by CYP2B6, with only 1% being eliminated in the urine unchanged, and a mean half-life of 3.5h. Hydroxybupropion, the major active metabolite of bupropion, has a longer half-life, reaches higher concentrations, and is renally cleared with significantly reduced clearance in renal failure patients (Costa, 2019).

The authors present a patient with chronic kidney disease (CKD) and major depressive disorder (MDD), treated with bupropion for many years. He was found to have significantly reduced clearance of hydroxybupropion while maintaining normal bupropion serum levels, which raised concerns regarding safety with use.

Case:
A 69-year-old male with a history of coronary artery disease, ischemic cardiomyopathy, CKD stage 3, and MDD treated with bupropion and vortioxetine for decades was hospitalized for orthotopic heart transplantation. Hospital course was complicated by encephalopathy, acute kidney injury, and cardiac arrest requiring cardioversion. Psychiatry was consulted and recommended continuing vortioxetine 15mg once daily and converting bupropion SR 100mg three times daily to bupropion XL 300mg once daily.

At his first outpatient psychiatry appointment following hospitalization, he reported no active symptoms of MDD or encephalopathy. MDD had remained in remission for decades and was historically aggravated by heavy alcohol use. He expressed desire to downtitrate his antidepressant medications due to concerns of CKD and polypharmacy. Creatine clearance was noted to be 39mL/min, so serum levels of bupropion and hydroxybupropion were obtained. Bupropion level was found to be 15ng/mL (normal range 10-100), and hydroxybupropion level was 1,730ng/mL (normal range 850-1500). Bupropion downtitration was thus initiated.

Discussion:
Therapeutic drug monitoring of bupropion appears to be rarely used clinically, but may play an important role in patients with CKD. While this patient had a normal bupropion level, the hydroxybupropion level was elevated and near the toxic range, consistent with normal hepatic function and significantly reduced renal function. Prior literature has advised dose reduction and raised concerns regarding the benefit of antidepressant use in patients with CKD (Nagler 2012).

Conclusions:
Bupropion should be used with caution in patients with renal failure, and psychiatrists should consider obtaining serum drug levels when appropriate.

References:

1. Khan SR et al (2016). Bupropion Hydrochloride. Profiles of drug substances, excipients, and related methodology, 41, 1–30.


2. Costa R et al (2019). Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects. Drug metabolism reviews, 51(3), 293–313.


3. Nagler EV et al (2012), 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), Nephrology Dialysis Transplantation, 27(10), 3736–3745.