What is the preferred treatment between bupropion and hydroxybupropion for conditions like major depressive disorder and smoking cessation?

Bupropion vs. Hydroxybupropion for Depression and Smoking Cessation

Bupropion is the preferred treatment over hydroxybupropion for both major depressive disorder and smoking cessation, as hydroxybupropion is actually the active metabolite of bupropion rather than a standalone medication. 1

Understanding Bupropion and its Metabolite

• Bupropion undergoes metabolic transformation to its active metabolite, 4-hydroxybupropion (hydroxybupropion), through hepatic cytochrome P450-2B6 (CYP2B6) 1
• Hydroxybupropion is not prescribed as a separate medication but is the active compound that contributes to bupropion's therapeutic effects 2
• Serum levels of hydroxybupropion correlate with therapeutic effects in depression treatment, with levels above 860 ng/mL associated with marked clinical improvement 2

Efficacy for Major Depressive Disorder

• Bupropion is FDA-approved as an antidepressant and has been shown to be effective for the long-term treatment of recurrent major depression 3
• The American College of Physicians recommends bupropion as one of the second-generation antidepressants that can be selected based on adverse effect profiles, cost, and patient preferences 3
• Unlike other antidepressants, bupropion has no serotonergic activity and works by inhibiting the reuptake of norepinephrine and dopamine 4
• At 300 mg daily, bupropion has demonstrated efficacy for treating major depression 3
• Bupropion is non-inferior to SSRIs such as escitalopram in treating major depressive disorder 4

Efficacy for Smoking Cessation

• Bupropion was first approved to treat depression, but its efficacy as a smoking cessation aid also became apparent 3
• A 2014 Cochrane review of 44 trials examining bupropion efficacy revealed a relative risk of 1.62 (95% CI, 1.49–1.76) for successful smoking cessation 3
• In the EAGLES trial (n=8,144), patients receiving bupropion achieved superior abstinence rates compared with placebo (OR, 2.07; 95% CI, 1.75–2.45) 3
• Bupropion may be particularly beneficial as a smoking cessation agent for persons with depression 3, 5
• Longer duration of bupropion treatment may help prevent relapse in those who have successfully quit smoking 3

Special Populations and Considerations

• For patients with both depression and tobacco use disorder:

  • Bupropion has demonstrated efficacy for smoking cessation independently of a former history of major depression 5
  • Studies show bupropion is effective when added to SSRI treatment in depressed patients trying to quit smoking 6
  • Minimal weight gain is observed during smoking cessation with bupropion, which is an advantage 6

• Gender differences:

  • Women attain significantly higher serum levels of hydroxybupropion than men under similar dosing and may exhibit better therapeutic effects 2

Safety and Adverse Effects

• Common side effects include nervousness and insomnia 1
• Bupropion has less sexual dysfunction compared to other antidepressants 1
• Bupropion reduces the seizure threshold and should be avoided in:
  • Patients with epilepsy 3
  • Patients with brain metastases who have a history or elevated risk of seizure 3
  • Those with clinical factors that may increase seizure risk 3
• Bupropion should not be combined with monoamine oxidase inhibitors 1
• Neuropsychiatric effects have been identified as a safety concern, although serious events are rare 3
• In the EAGLES trial, no significant increase in neuropsychiatric events was observed for bupropion relative to nicotine patch or placebo 3
• Recent meta-analyses do not show elevated risk of serious adverse cardiovascular effects with bupropion use for smoking cessation 3

Dosing Considerations

• For depression: Standard dose is typically 300 mg per day 3
• For smoking cessation: The dose is similar to that used for depression 3
• In patients with moderate to severe hepatic impairment, the total daily dose should be reduced 3
• In patients with moderate to severe renal impairment, the total daily dose should be reduced by one-half 3

Monitoring and Follow-up

• Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 3
• Treatment should be modified if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks 3
• Patients should be monitored for the emergence of agitation, irritability, or unusual changes in behavior 3
• Measuring 4-hydroxybupropion in serum can be useful for therapeutic drug monitoring 2