II. 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. Selective Serotonin Reuptake Inhibitor (SSRI) Failure
    2. Adjunctive therapy in combination with SSRI
  3. Other uses (off label)
    1. Attention Deficit Disorder
    2. Obesity Management
    3. Sexual Dysfunction
    4. Abuse potential (recreational drug use)

III. Precautions

  1. FDA Pregnancy Category C
  2. FDA Black Box Warning
    1. Increased risk of Suicidality in patients with Major Depression

IV. Efficacy: Smoking Cessation (with concurrent counseling)

  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]

V. 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

VI. Dosing: Major Depression

  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
    3. Maximum: 150 mg orally three times daily

VII. Dosing: Smoking Cessation

  1. Protocol (May substitute 2 of Wellbutrin 75 mg)
    1. Start: Bupropion 150 mg XR orally daily for 3 days
    2. Then: Bupropion 150 mg XR 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. Cost: $186/10 week supply (wholesale)
    4. Minimum of 8 hours between doses
    5. More is not better
    6. Swallow pills whole (not crushed, divided or chewed)

VIII. Dosing: Combination - Auvelity (Bupropion/Dextromethorphan)

  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

IX. Pharmacokinetics

  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

X. Drug Interactions

  1. Prozac associated with panic and Psychosis
  2. Increased toxicity with:
    1. MAO inhibitor
    2. Ritonavir
  3. Carbamazepine (Tegretol) increases metabolism

XI. Contraindications

  1. Seizure Disorder
  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

XII. Adverse Effects: Dopaminergic effects

  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 dose to 150 mg q6 hours

XIII. Management: Overdose

XIV. Advantages

  1. No Anticholinergic Toxicity
  2. No Antihistaminergic activity
  3. No cardiac toxicity
  4. No sexual side effects

XV. Resources: Tobacco Cessation Counseling

  1. Zyban Advantage Plan
    1. Free 3 month program to users of product
  2. Tobacco Cessation counseling course

XVI. References

  1. Sundberg (1995) Depression Primary Care, PGM, p. 45-57
  2. Mallin (2002) Am Fam Physician 65(6):1107-17 [PubMed]

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Cost: Medications

bupropion (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
BUPROPION HCL 100 MG TABLET Generic $0.31 each
BUPROPION HCL 75 MG TABLET Generic $0.25 each
BUPROPION HCL SR 100 MG TABLET Generic $0.20 each
BUPROPION HCL SR 150 MG TABLET Generic $0.15 each
BUPROPION HCL SR 200 MG TABLET Generic $0.30 each
BUPROPION HCL XL 150 MG TABLET Generic $0.40 each
BUPROPION HCL XL 300 MG TABLET Generic $0.50 each
wellbutrin (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
WELLBUTRIN SR 100 MG TABLET Generic $0.20 each
WELLBUTRIN SR 150 MG TABLET Generic $0.15 each
WELLBUTRIN SR 200 MG TABLET Generic $0.30 each
WELLBUTRIN XL 150 MG TABLET Generic $0.40 each
WELLBUTRIN XL 300 MG TABLET Generic $0.50 each