bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)

Introduction

Tradename: Wellbutrin.

Indications

• depression, especially with anergia &/or hypersomnia
  • start 100 mg PO BID
  • after 4-7 days, can increase to 100 mg TID
  • max 150 mg/dose, 450 mg/day
  • average effective dose 300-450 mg/day
  • sustained release (Wellbutrin SR)
    • start 150 mg PO QAM
    • may increase to 150 mg PO BID
• attention-deficit hyperactivity disorder (ADHD) in adults
• smoking cessation (sustained release)*
  • start 150 mg QAM for 3 days
  • increase to 150 mg PO BID for 7-12 days to 7 weeks
  • last dose no later than 5 pm
  • max dose 150 mg PO BID double rate of smoking cessation
  • quit date should be 1 week after starting therapy to achieve steady-state level
  • stop if no progress in smoking cessation by 7th week
• sexual dysfunction in women
  • may be used in combination with SSRI
  • erectile dysfunction in men with comorbid depression (NEJM)
• good choice for depression in Parkinson's disease
• neuropathic pain
• seasonal affective disorder (Wellbutin XL)
• mania

* avoid for smoking cessation

• risk of neuropsychiatric disorders cited

Contraindications

• seizures
• bulimia
• anorexia
• use of monoamine oxidase (MAO) inhibitor within past 14 days

Caution:

• allow 8 hours between doses
• avoid alcohol
• safety of use in children < 18 years of age has NOT been established

pregnancy category = b

safety in lactation = -

Dosage

• adults
  • start: 100 mg PO BID
  • maximum 450 mg QD, 150 mg/dose
  • usual dose 250-300 mg/day divided BID-TID
• elderly patients:
  • start: 50-100 mg/day
  • increase by 50-100 mg every 3-4 days as tolerated
  • usual effective dose: 150 mg QD

Tabs: 75 & 100 mg

Sustained release:

• Wellbutrin SR: 75, 100 & 150 mg. (BID dosing)
• Wellbutrin XL: 150, 300 mg (QD dosing)

Alpenzin is the hydrobromide salt of bupropion

Dosage adjustment in renal failure

(& hepatic impairment)

• use reduced dose
• use with caution

Pharmacokinetics

• bioavailability is low (5%), not affected by food
• peak plasma levels 2 hours after oral dose (5 hours for XL)
• > 80% bound to plasma proteins
• metabolites accumulate in patients with renal or hepatic dysfunction
• active metabolite hydroxybupropion
  • 1/2life > 24 hours
  • LD50 in mice 1/2 that of bupropion
• therapeutic window of 50-100 ng/mL
• no correlation between dose & response or plasma levels
• inhibits cyt P450 2D6, thus may increase plasma levels of drugs metabolized by cyt P450 2D6

elimination via kidney

1/2life = 9.6-21 hours

protein binding = 80 %

elimination by hemodialysis = -

elimination by peritoneal dialysis = -

Adverse effects

• common (> 10%)
  • agitation, anxiety, restlessness, insomnia, confusion, constipation, anorexia, dizziness, dry mouth, increased sweating, nausea/vomiting, tremor, weight loss
• less common (1-10%)
  • psychosis & hallucinations, skin rash, blurred vision, chills, fatigue
• uncommon (< 1%)
  • fainting, drowsiness, seizures*
• other
  • insomnia, agitation, headache, tinnitus, rash, diarrhea, tachycardia, akathisia, impotence, hostility, agitation, depression, suicidal ideation#
  • no excess risk for depression or self-harm
  • not associated with increased cardiovascular risk
  • reduced risk for combined outcome of stroke, MI, & cardiovascular death (RR=0.45)
  • not associated with excess risk for neuropsychiatric events when used for smoking cessation
  • less likely than venlafaxine to cause GI distress
• overdose results in:
  • seizures (most common)
  • prolongation of the QT interval

* increased potential with daily doses of 450-600 mg/day limit single doses to < 150 mg & daily doses to < 300 mg

# risk of serious side effects on mood, behavior, or thinking lower than previously suspected

• drug adverse effects of antidepressants
• drug adverse effects of psychotropic agents

Drug interactions

• L-dopa: higher incidence of adverse effects
• monoamine oxidase inhibitors
  • acute toxicity may be enhanced
  • discontinue MAO inhibitors at least 14 days before starting bupropion
• concurrent use of alcohol, tricyclic antidepressants (TCA) fluoxetine (Prozac) or phenothiazines lowers seizure threshold
• cimetidine & ritonavir decrease bupropion metabolism
• bupropion may increase metabolism of:
  • carbamazepine
  • phenytoin
  • phenobarbital
  • cimetidine
• no known interaction with warfarin

• drug interaction(s) of antidepressant in combination with GLP1-agonist
• drug interaction(s) of benzodiazepines with antidepressants
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of NSAIDs with antidepressants
• drug interaction(s) of antidepressant with opiates

Laboratory

• specimen:
  • plasma (heparin)
  • bupropion is unstable in human plasma
  • freeze soon after collection
  • stable frozen for 6 months
• methods: HPLC, TLC, GC, RIA

Mechanism of action

• monocyclic antidepressant
• inhibits reuptake of norepinephrine & dopamine

More general terms

• norepinephrine & dopamine reuptake inhibitor (NDRI)

Component of

• bupropion/dextromethorphan (Auvelity)
• bupropion/naltrexone (Contrave)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=444
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62884
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657316