Bupropion (Wellbutrin®) versus Duloxetine (Cymbalta®)

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

Bupropion advantages over Duloxetine

  • Does not cause in sexual problems, hypertension, or urinary retention.
  • Safe for patients with increased intraocular pressure.

Duloxetine advantages over Bupropion

  • Large body of evidence of duloxetine efficacy in chronic pain syndromes.
  • Duloxetine can be useful for patients with concomitant chronic pain issues or anxiety.
  • Suitable for patients with eating disorders or with risk of seizures.


Main differences between Bupropion and Duloxetine

Bupropion Duloxetine
Brand names
• Wellbutrin® • Cymbalta®
Drug class
Antidepressant, Norepinephrine-dopamine reuptake inhibitor Antidepressant, Serotonin-norepinephrine reuptake inhibitor
Mechanism of action
• Blocks the reabsorption of norepinephrine and dopamine.
• Bupropion has mild stimulant effects.
• Blocks the reabsorption of serotonin and noradrenaline.
• Duloxetine also inhibits dopamine reuptake to a lesser extent.
FDA-approved indications
• Major depression
• Seasonal affective disorder
• Smoking cessation
• Generalized anxiety disorder
• Social anxiety disorder
• Chronic musculoskeletal pain
• Fibromyalgia
• Diabetic peripheral neuropathic pain
• Hypersensitivity to bupropion
• Seizure disorder
• Conditions that increase the risk of seizures, e.g. severe head trauma, CNS infection, anorexia nervosa, bulimia nervosa, benzodiazepine withdrawal
• Concomitant use of MAOIs
• Hypersensitivity to duloxetine
• Uncontrolled narrow-angle glaucoma (risk of increased intraocular pressure)
Frequent adverse effects
Headache, dry mouth, nausea, insomnia 3, agitation, aggravation of psychosis. Nausea, somnolence, headache, insomnia, dizziness, constipation, and dry mouth 2.
Other notes
Bupropion is particularly useful for patients suffering from sexual dysfunction or excessive sedation caused by other medications. Duloxetine is may be useful for patients who have concomitant pain symptoms.

SSRI-resistant major depression

Results of randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant depression 1. Bupropion XL Duloxetine
Response rates
60 to 70%
60 to 70%
Remission rates
30 to 40%
30 to 40%
Conclusion Patients who do not respond sufficiently to SSRIs may be treated with antidepressants that have different mechanisms of action

Further reading


  • 1. Rosso G, Rigardetto S, Bogetto F, Maina G. A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression. J Affect Disord. 2012 Jan;136(1-2):172-6. PubMed
  • 2. Carter NJ, McCormack PL. CNS Drugs. 2009;23(6):523-41. PubMed
  • 3. Aubin HJ. Drugs. 2002;62 Suppl 2:45-52. PubMed

Published: March 24, 2014
Last updated: October 24, 2017


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