Bupropion (Wellbutrin®) versus Venlafaxine (Effexor®)

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

Bupropion advantages over Venlafaxine

  • Unlike venlafaxine, bupropion does not require blood pressure monitoring.
  • It is not as nauseous as venlafaxine.
  • The incidence and severity of withdrawal syndrome is significantly lower.
  • Bupropion may be particularly useful in patients with psychomotor retardation, Parkinson's disease, attention deficit/hyperactivity disorder, and those who is quitting smoking.

Venlafaxine advantages over Bupropion

  • Does not produce meaningful inhibition of drug metabolizing CYP enzymes.
  • No risk of seizures. Suitable for patients with a history of seizure.
  • Unlike bupropion, venlafaxine is effective for various anxiety disorders.


Main differences between Bupropion and Venlafaxine

Bupropion Venlafaxine
Brand names
• Wellbutrin® • Effexor®
Drug class
Antidepressant, Norepinephrine-dopamine reuptake inhibitor Antidepressant, Serotonin-norepinephrine reuptake inhibitor
FDA-approved indications
• Major depression
• Seasonal affective disorder
• Smoking cessation
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder
• Hypersensitivity to bupropion
• Seizure disorder
• Bulimia or anorexia nervosa
• Abrupt discontinuation of alcohol or sedatives
• Concomitant use with MAOIs
• Hypersensitivity to venlafaxine
• Concomitant use with MAOIs
• Risk of seizures • Sustained hypertension
Drug interactions
• Potential for a drug interaction between bupropion and other drugs that inhibit or induce CYP2B6 isoenzyme • Low potential for pharmacokinetic drug interactions
Effects on sexual function
May improve sexual function Adverse effects on sexual function1
Weight changes
Often causes weight loss May cause weight gain 5
Abuse potential
• In comparison with venlafaxine bupropion is more frequently used for non-medical purposes.
• However, bupropion causes dependence and withdrawal problems less frequently 6.

Head-to-head comparative studies

Results of double-blind comparison between bupropion XL and venlafaxine XR for depression in relatively young, sexually active patients 1. Bupropion SR Venlafaxine
Changes in Sexual Functioning Questionnaire (self-report) increased decreased
Changes on the 17-item Hamilton Depression Rating Scale
Remission rates

Results of placebo-controlled, double-blind comparison of bupropion XR and venlafaxine XR for major depressive disorder2. Bupropion SR Venlafaxine XR
Mean changes from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF)
Most frequently reported side effects dry mouth and insomnia nausea, hyperhidrosis (excessive sweating), fatigue, and insomnia
Conclusion Comparable antidepressant efficacy

Adjunctive treatment of bipolar depression
Results of comparison of adjunctive venlafaxine and bupropion in bipolar depression 4. Bupropion Venlafaxine
Acute response
Risk of switches into hypomania or mania significantly increased risk of switches into hypomania or mania in patients treated with venlafaxine compared with bupropion


Further reading


  • 1. Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA. A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol. 2006 Oct;26(5):482-8. PubMed
  • 2. Hewett K, Chrzanowski W, Schmitz M, Savela A, Milanova V, Gee M, Krishen A, Millen L, Leary MO, Modell J. Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. J Psychopharmacol. 2009 Jul;23(5):531-8. PubMed
  • 3. Hewett K, Gee MD, Krishen A, Wunderlich HP, Le Clus A, Evoniuk G, Modell JG. Double-blind, placebo-controlled comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. J Psychopharmacol. 2010 Aug;24(8):1209-16 PubMed
  • 4. Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW, Suppes T, McElroy S, Keck PE, Denicoff KD, Grunze H, Walden J, Kitchen CM, Mintz J. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006 Aug;189:124-31. PubMed
  • 5. Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R. Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry. 2015 Jan-Feb;37(1):46-8. PubMed
  • 6. Schifano F, Chiappini S. Is There a Potential of Misuse for Venlafaxine and Bupropion? Front Pharmacol. 2018 Mar 21;9:239. PubMed

Published: March 24, 2014
Last updated: August 12, 2018


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