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Bupropion

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Bupropion, Wellbutrin, Zyban, Norepinephrine Dopamine Reuptake Inhibitor, NDRI, Auvelity, Aplenzin, Buproban, Forfivo XL

  • See Also
  1. Bupropion Overdose
  • Indications
  1. Tobacco Cessation (Zyban)
    1. May be used in combination with Nicotine Replacement
    2. Not considered first-line therapy for adolescents
  2. Reasonable second line Antidepressant in Major Depression
    1. Adjunctive therapy in combination with SSRI
      1. Add to Selective Serotonin Reuptake Inhibitor (SSRI) when SSRI insufficient alone
  3. Other uses (off label)
    1. Attention Deficit Disorder
    2. Obesity Management
    3. Sexual Dysfunction
    4. Seasonal effective disorder
  4. Abuse potential (recreational drug use)
    1. Has been inhaled or injected illicitly, with risk of Seizure and death
  • Precautions
  1. FDA Pregnancy Category C
  2. Avoid in Lactation
  3. FDA Black Box Warning
    1. Increased risk of Suicidality in patients with Major Depression
  1. Predictors of quitting with Bupropion
    1. Higher dose (Bupropion 300 mg/day divided twice daily)
    2. Male gender
    3. Prior Tobacco abstinence previously
    4. Abstinence for >2 weeks with current attempt
  2. Quit Rates (Study: n=893 over 10 weeks)
    1. Note these rates are higher than with other studies
    2. Placebo: 20% quit
    3. Transdermal Nicotine (21 mg): 32% quit
    4. Bupropion SR 150 mg bid: 46% quit
    5. Bupropion and Transdermal Nicotine: 51% quit
  3. Reference
    1. (1997) Med Lett Drugs Ther 39(1007):77-8 [PubMed]
    2. Dale (2001) Chest 119:1357-64 [PubMed]
  • Mechanism
  1. Monocyclic aminoketone
    1. Structurally similar to Amphetamine
  2. Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
    1. Marked Norepinephrine reuptake inhibitor effect
    2. Also has Dopamine reuptake inhibitor activity
    3. Some selective Dopamine reuptake inhibitor effect
  3. Smoking Cessation effect
    1. Enhances Dopamine levels in the mesolimbic system
      1. Reduces desire for Nicotine dramatically
    2. Affects noradrenergic Neurons in the locus ceruleus
      1. Reduces Nicotine withdrawal symptoms
  1. Bupropion Immediate Release Tablets
    1. Elderly: 100 mg orally twice daily
    2. Usual dosing
      1. Initial: 100 mg orally twice daily for 4 days
      2. Next: 100 mg orally three times daily (at least 6 hours between doses)
      3. Maximum: 150 mg orally three times daily (450 mg/day)
  2. Bupropion Sustained Release Tablets (Bupropion SR, Wellbutrin SR)
    1. Start 150 mg orally daily each morning
    2. May increase to 150 mg orally twice daily after 3 or more days
    3. Maximum: 200 mg orally twice daily (400 mg/day)
      1. Moderate to severe hepatic Impairment: 100 mg/day or 150 mg every other day
  3. Bupropion Extended Release Tablets (Bupropion XL, Wellbutrin XL)
    1. Start 150 mg orally daily each morning
    2. May increase after 4 or more days to maximum of 300 mg orally each morning
  4. Bupropion Extended Release (Aplenzin)
    1. Start 174 mg orally every morning
    2. May increase to target dose after 4 or more days to 348 mg orally each morning
    3. Maximum: 522 mg/day (if transitioning from prior Bupropion immediate release 450 mg/day)
  5. Bupropion Extended Release (Forfivo XL)
    1. Take 450 mg orally daily in morning
    2. Use only when transitioning patients already on max dose Wellbutrin (e.g. immediate release 450 mg/day)
  1. Protocol (May substitute 2 of Bupropion immediate release 75 mg)
    1. Start: Bupropion 150 mg SR orally daily in morning for 3 days
    2. Then: Bupropion 150 mg SR orally twice daily for 7-12 weeks
  2. General
    1. Stop smoking during second week of medication
    2. Stop Bupropion if unable to quit by 7 weeks
    3. Minimum of 8 hours between doses
    4. Take second dose by 5 pm to avoid interference with sleep
    5. Higher dosing is not better
    6. Swallow pills whole (not crushed, divided or chewed)
  1. Auvelity taken orally twice daily
    1. Bupropion 105 mg/tablet
    2. Dextromethorphan 45 mg/tablet
  2. Mechanism
    1. Bupropion, in addition to Antidepressant effects, also increases Dextromethorphan levels via CYP2D6 inhibition
    2. Dextromethorphan is proposed to have Antidepressant effect
  3. Precautions
    1. See Dextromethorphan Toxicity (including Serotonin Syndrome)
    2. New combination released in 2022, with limited efficacy data, and a monthly cost > $1000
      1. At time of 2022 release, no evidence of benefit over standard SSRI, SNRI agents at monthly costs < $10-30
  4. References
    1. (2022) Presc Lett 29(12): 69-70
  • Pharmacokinetics
  • Bupropion Regular Release
  1. Rapid gastrointestinal absorption
  2. Peak Concentration at 3-5 hours
  3. Serum Half Life: >15-20 hours
  4. Therapeutic Blood Level: 50-100 ng/ml
  • Drug Interactions
  1. Fluoxetine (Prozac)
    1. Associated with panic and Psychosis
  2. Avoid with MAO Inhibitor (Serotonin Syndrome risk), including Linezolid
  3. Increased toxicity with Ritonavir
  4. Carbamazepine (Tegretol) increases metabolism
  5. Increased Blood Pressure when combined with agents increasing Norepinephrine or Dopamine
  6. May cause False Positive immunoassay Urine Drug Screen for Amphetamines
  • Contraindications
  1. Seizure Disorder
    1. Also avoid when Seizure risk is increased (e.g. Alcohol Withdrawal)
  2. Concurrent psychiatric medications
    1. MAO Inhibitor (allow 14 day interval between these two Medication Classes)
    2. Ritonavir
    3. Other forms of Bupropion (Wellbutrin, Zyban)
  3. Eating Disorder
    1. Anorexia Nervosa
    2. Bulimia
  4. Pregnancy
  5. Uncontrolled Hypertension
  1. Very Activating, Agitation
    1. Good choice in withdrawn people
    2. Decreases in 1-2 weeks after starting medication
    3. Consider starting with Benzodiazepine and tapering
  2. Insomnia (35-40%)
  3. Dry Mouth (10%)
  4. Restlessness
  5. Tremor
  6. Gastrointestinal upset
  7. Headache
  8. Appetite suppression and weight loss
    1. Avoid in Eating Disorders
  9. Lowers Seizure threshold
    1. Avoid if concurrent Seizure Disorder
    2. Avoid in abrupt cessation of Alcohol, Barbiturates, Benzodiazepines or antiepileptics (risk of withdrawal Seizure)
    3. Seizure Incidence
      1. Regular release: 1%
        1. Increased with dose >150 mg/dose or 450 mg/day
      2. Sustained release: 0.1%
        1. Increased with dose >200 mg/dose or 400 mg/day
    4. Minimize risk by limiting to lower dose
  10. Neuropsychiatric effects in patients using Bupropion for Tobacco Cessation
    1. Psychosis (Hallucinations, Delusions, mania, homicidal ideation)
    2. Mood and behavior effects (anxiety, depression, Suicidality, hostility, Agitation, aggression)
  1. See Bupropion Overdose
  • Advantages
  1. No Anticholinergic Toxicity
  2. No Antihistaminergic activity
  3. No cardiac toxicity
  4. No sexual side effects
  • Resources
  1. See Tobacco Cessation
  2. Bupropion (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4100232-a25d-4468-9057-af7e66205154
  • References
  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. Sundberg (1995) Depression Primary Care, PGM, p. 45-57
  5. Mallin (2002) Am Fam Physician 65(6):1107-17 [PubMed]