Bupropion (Wellbutrin®) versus Escitalopram (Lexapro®)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Bupropion advantages over Escitalopram

  • Bupropion works better for sleepiness and fatigue in patients with depression4.
  • Bupropion has no negative impact on sexual function.
  • Bupropion has the lowest incidence of weight gain and sedation.
  • Bupropion may be added to the treatment regimen for depression partially or not responding to SSRI antidepressant5.
  • Escitalopramis associated with decreased platelet count, and bupropion is less likely to influence platelet count1.

Escitalopram advantages over Bupropion

  • Suitable for patients with seizure disorders, anorexia, or bulimia.
  • Escitalopram has anxiolytic activity.
  • Escitalopram has a relatively low potential for drug-drug interactions.


Difference between Bupropion and Escitalopram

Bupropion Escitalopram
Brand names
Wellbutrin SR®
Wellbutrin XL®
Drug class
Norepinephrine-Dopamine Reuptake Inhibitor Selective Serotonin Reuptake Inhibitor
Dose formulations
• Tablets
• Tablets, sustained-release
• Tablets, extended release
• Tablets
• Solution, oral
Legal status
• Rx only
• Not a controlled drug
FDA-approved indications
• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation
• Generalized anxiety disorder
"Off-label" uses
• Obesity
• Antidepressant-induced sexual dysfunction
• Depression associated with bipolar disorder
• Social anxiety
• Panic disorder
• Vasomotor symptoms associated with menopause (hot flashes)excessive internet game playing
• Excessive internet game playing8
Mechanism of action
• Enhances neurotransmission via inhibition of norepinephrine and dopamine reuptake.
• No noticeable serotonergic activity.
• Escitalopram is the most selective SSRI antidepressant and has little or no affinity for other neurotransmitter receptors.
• 8-24 hours (immediate-release)
• 21 +/- 7 hours (extended-release)
• 27-32 hours
Oral bioavailability
5% to 20% 80%
Metabolism, Elimination
• Bupropion is extensively metabolized via CYP2B6.
• Three active metabolites: hydroxybupropion, threohydrobupropion and erythrohydrobupropion.
• Excretion: urine 87%, feces 10%.
• Escitalopram is metabolized via hepatic isoenzymes CYP2C19 and CYP3A4.
• Excretion: urine 8% as unchanged drug; metabolite S-desmethylcitalopram 10%.
• Use of MAO inhibitors
• Hypersensitivity to bupropion
• History of anorexia or bulimia
• Seizure disorder
• Abrupt discontinuation of alcohol or sedatives (including benzodiazepines)
• Other formulations of bupropion
• Hypersensitivity to escitalopram or citalopram
• Initiation of escitalopram in a patient receiving linezolid or intravenous methylene blue
• Use of pimozide
Side effects
• Headache
• Dry mouth
• Nausea
• Insomnia
• Anorexia
• Weight loss
• Agitation
• Dizziness
• Constipation
• Anxiety
• Diarrhea
• Tinnitus
• Tremor
• Nervousness
• Headache
• Nausea
• Diarrhea
• Ejaculation disorder
• Drowsiness
• Insomnia
• Dry mouth
• Constipation
• Fatigue
• Libido decrease
• Anorgasmia
• Weight gain
Drug interactions
• Drugs that are metabolized by CYP2D6 isoenzyme (e.g., beta-blockers, antiarrhythmics, and antipsychotics)
• Drugs that lower seizure threshold (e.g., antipsychotics, theophylline, systemic steroids, etc.)
• Escitalopram has little or no effect on the CYP pathways

Head-to-head comparative studies


Results of 2 randomized, double-blind, placebo-controlled studies of bupropion extended release versus escitalopram 2. Bupropion XL Escitalopram
Orgasm dysfunction, % of patients in study 1 13% 32%
Orgasm dysfunction, % of patients in study 2 16% 29%
17-item Hamilton Rating Scale for Depression remission rates and Hospital Anxiety and Depression total scores in patients with MDD

Generalized Anxiety Disorder

Results of pilot controlled trial of bupropion XL versus escitalopram in generalized anxiety disorder 3. Bupropion XL Escitalopram
Anxiolytic efficacy

Internet Gaming Disorder

Both bupropion and escitalopram are effective in managing symptoms of Internet gaming disorder7. Bupropion improves attention and reduces impulsivity better than escitalopram8.


Further reading


  • 1. Song HR, Jung YE, Wang HR, et al. Platelet count alterations associated with escitalopram, venlafaxine and bupropion in depressive patients.Psychiatry ClinNeurosci. 2012 Aug;66(5)
  • 2. Clayton AH, Croft HA, Horrigan JP, Wightman DS, Krishen A, Richard NE, Modell JG. 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 May;67(5):736-46. PubMed
  • 3. Bystritsky A, Kerwin L, Feusner JD, Vapnik T.A pilot controlled trial of bupropion XL versus escitalopram in generalized anxiety disorder. Psychopharmacol Bull. 2008;41(1):46-51.
  • 4. Cooper JA, Tucker VL, Papakostas GI. Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in major depressive disorder achieving remission at doses approved in the European Union. J Psychopharmacol. 2014 Feb;28(2):118-24.
  • 5. Fava M, Papakostas GI, Petersen T, et al. Switching to bupropion in fluoxetine-resistant major depressive disorder.Ann Clin Psychiatry. 2003 Mar;15(1):17-22
  • 6. Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, Ascher JA, Lineberry CG. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991 Aug;52(8):329-35. PubMed
  • 7. Song J, Park JH, Han DH, et al. Comparative study of the effects of bupropion and escitalopram on Internet gaming disorder. Psychiatry Clin Neurosci. 2016 Nov;70(11):527-535 PubMed
  • 8. Nam B, Bae S, Kim SM, Hong JS, Han DH. Comparing the Effects of Bupropion and Escitalopram on Excessive Internet Game Play in Patients with Major Depressive Disorder. Clin Psychopharmacol Neurosci. 2017 Nov 30;15(4):361-368.

Published: March 31, 2008
Last updated: August 12, 2018


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