bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)

^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]

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^[20]
- 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^[6]
- may be used in combination with SSRI^[26]
- erectile dysfunction in men with comorbid depression (NEJM)^[26]
good choice for depression in Parkinson's disease
neuropathic pain^[9]
seasonal affective disorder (Wellbutin XL)
mania^[16]

* avoid for smoking cessation^[22]

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^[14]#
- no excess risk for depression or self-harm^[17]
- not associated with increased cardiovascular risk^[18]
- reduced risk for combined outcome of stroke, MI, & cardiovascular death (RR=0.45)^[18]
- not associated with excess risk for neuropsychiatric events when used for smoking cessation^[19]
- less likely than venlafaxine to cause GI distress^[25]
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^[3]

# risk of serious side effects on mood, behavior, or thinking lower than previously suspected^[21]

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:
no known interaction with warfarin^[25]

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

References

↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
↑ ^{Jump up to: 3.0} ^3.1 Kaiser Permanente Northern California Regional Drug Formulary, 1998
↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
↑ Prescriber's Letter 8(4):23 2001
↑ ^{Jump up to: 6.0} ^6.1 Prescriber's Letter 8(6):34 2001
↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
↑ Journal Watch 21(20):162, 2001 Hayes et al, Ann Intern Med 135:423, 2002
↑ ^{Jump up to: 9.0} ^9.1 Journal Watch 22(1):10, 2002 Semenchunk et al, Neurology 57:1583, 2001
↑ Prescriber's Letter 9(3):13-14 2002
↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
↑ Prescriber's Letter 10(10):57 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=191003&pb=PRL (subscription needed) http://www.prescribersletter.com
↑ Prescriber's Letter 13(9): 2006 Drug Treatment of Seasonal Affective Disorder (SAD) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220904&pb=PRL (subscription needed) http://www.prescribersletter.com
↑ ^{Jump up to: 14.0} ^14.1 FDA Safety Alert Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170090.htm
↑ Stahl SM et al A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor Prim Care Companion J Clin Psychiatry. 2004; 6(4):159-166 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/ http://www.bmj.com/content/347/bmj.f5704http://www.bmj.com/content/347/bmj.f5704
↑ ^{Jump up to: 16.0} ^16.1 Deprecated Reference
↑ ^{Jump up to: 17.0} ^17.1 Thomas KH et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: Prospective cohort study. BMJ 2013 Oct 11; 347:f5704. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24124105 <Internet> http://www.bmj.com/content/347/bmj.f5704
↑ ^{Jump up to: 18.0} ^18.1 ^18.2 Mills EJ et al Cardiovascular Events Associated with Smoking Cessation Pharmacotherapies: A Network Meta-Analysis. Circulation. Dex 9, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24323793 <Internet> http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.003961.abstract
Samet J Smoking Cessation: Benefits versus Risks of Using Pharmacotherapy to Quit. Circulation. Dex 9, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24323794 <Internet> http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.006928.abstract
↑ ^{Jump up to: 19.0} ^19.1 Anthenelli RM et al Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo- controlled clinical trial. The Lancet. April 22, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27116918 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2930272-0/abstract
↑ ^{Jump up to: 20.0} ^20.1 Fossati R, Apolone G, Negri E et al A double-blind, placebo-controlled, randomized trial of bupropion for smoking cessation in primary care. Arch Intern Med. 2007 Sep 10;167(16):1791-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17846399
↑ ^{Jump up to: 21.0} ^21.1 FDA Safety Alert. Dec 16, 2016 Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533517.htm
FDA Safety Aommunication. Dec 16, 2016 FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm
↑ ^{Jump up to: 22.0} ^22.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
↑ Clayton AH, Croft HA, Horrigan JP et al. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry 2006 Jul 18; 67:736. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16841623
↑ Patel K, Allen S, Haque MN et al. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol 2016 Apr; 6:99. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27141292 Free PMC Article
↑ ^{Jump up to: 25.0} ^25.1 ^25.2 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
↑ ^{Jump up to: 26.0} ^26.1 ^26.2 NEJM Knowledge+ Psychiatry

Database

[ref1-1] The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996

[ref2-2] Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998

[ref3-3] {Jump up to: 3.0} ^3.1 Kaiser Permanente Northern California Regional Drug Formulary, 1998

[ref4-4] Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995

[ref5-5] Prescriber's Letter 8(4):23 2001

[ref6-6] {Jump up to: 6.0} ^6.1 Prescriber's Letter 8(6):34 2001

[ref7-7] UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001

[ref8-8] Journal Watch 21(20):162, 2001 Hayes et al, Ann Intern Med 135:423, 2002

[ref9-9] {Jump up to: 9.0} ^9.1 Journal Watch 22(1):10, 2002 Semenchunk et al, Neurology 57:1583, 2001

[ref10-10] Prescriber's Letter 9(3):13-14 2002

[ref11-11] Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001

[ref12-12] Prescriber's Letter 10(10):57 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=191003&pb=PRL (subscription needed) http://www.prescribersletter.com

[ref13-13] Prescriber's Letter 13(9): 2006 Drug Treatment of Seasonal Affective Disorder (SAD) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220904&pb=PRL (subscription needed) http://www.prescribersletter.com

[ref14-14] {Jump up to: 14.0} ^14.1 FDA Safety Alert Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170090.htm

[ref15-15] Stahl SM et al A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor Prim Care Companion J Clin Psychiatry. 2004; 6(4):159-166 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/ http://www.bmj.com/content/347/bmj.f5704http://www.bmj.com/content/347/bmj.f5704

[ref16-16] {Jump up to: 16.0} ^16.1 Deprecated Reference

[ref17-17] {Jump up to: 17.0} ^17.1 Thomas KH et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: Prospective cohort study. BMJ 2013 Oct 11; 347:f5704. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24124105 <Internet> http://www.bmj.com/content/347/bmj.f5704

[ref18-18] {Jump up to: 18.0} ^18.1 ^18.2 Mills EJ et al Cardiovascular Events Associated with Smoking Cessation Pharmacotherapies: A Network Meta-Analysis. Circulation. Dex 9, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24323793 <Internet> http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.003961.abstract
Samet J Smoking Cessation: Benefits versus Risks of Using Pharmacotherapy to Quit. Circulation. Dex 9, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24323794 <Internet> http://circ.ahajournals.org/content/early/2013/11/25/CIRCULATIONAHA.113.006928.abstract

[ref19-19] {Jump up to: 19.0} ^19.1 Anthenelli RM et al Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo- controlled clinical trial. The Lancet. April 22, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27116918 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2930272-0/abstract

[ref20-20] {Jump up to: 20.0} ^20.1 Fossati R, Apolone G, Negri E et al A double-blind, placebo-controlled, randomized trial of bupropion for smoking cessation in primary care. Arch Intern Med. 2007 Sep 10;167(16):1791-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17846399

[ref21-21] {Jump up to: 21.0} ^21.1 FDA Safety Alert. Dec 16, 2016 Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm533517.htm
FDA Safety Aommunication. Dec 16, 2016 FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm

[ref22-22] {Jump up to: 22.0} ^22.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/

[ref23-23] Clayton AH, Croft HA, Horrigan JP et al. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry 2006 Jul 18; 67:736. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16841623

[ref24-24] Patel K, Allen S, Haque MN et al. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol 2016 Apr; 6:99. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27141292 Free PMC Article

[ref25-25] {Jump up to: 25.0} ^25.1 ^25.2 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019

[ref26-26] {Jump up to: 26.0} ^26.1 ^26.2 NEJM Knowledge+ Psychiatry

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bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)

Contents

Introduction

Indications

Contraindications

Dosage

Dosage adjustment in renal failure

Pharmacokinetics

Adverse effects

Drug interactions

Laboratory

Mechanism of action

More general terms

Component of

References

Database

Navigation menu

bupropion (Wellbutrin, Wellbutrin SR, Zyban, Aplenzin)

Introduction

Indications

Contraindications

Dosage

Dosage adjustment in renal failure

Pharmacokinetics

Adverse effects

Drug interactions

Laboratory

Mechanism of action

More general terms

Component of

References

Database

Navigation menu

Search