Sertraline (Zoloft®) vs Bupropion (Wellbutrin®)

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

Sertraline advantages over Bupropion

  • Sertraline has more reliable cardiovascular safety. It is proven to be safe in patients with recent myocardial infarction or angina 1. Although bupropion is generally regarded as safe in patients with cardiovascular diseases, it may cause minor increase in blood pressure 2.
  • Sertraline has a relatively low potential to interfere with CYP isoenzymes and is therefore a good choice for persons taking multiple medications.
  • Sertraline is an acceptable antidepressant for use during breastfeeding. This is supported by absence of short term adverse events and undetectable serum levels in infants3.

Bupropion advantages over Sertraline

  • Unlike sertraline, bupropion does not negatively affect sexual function.
  • Bupropion has minimal risk of weight gain.
  • Drowsiness and sleepiness are very unlikely.


Sertraline Bupropion
Brand names
Zoloft® Wellbutrin®
Wellbutrin SR®
Wellbutrin XL®
Drug class
Selective Serotonin Reuptake Inhibitor Norepinephrine-Dopamine Reuptake Inhibitor
Dose formulations
• Tablets
• Oral concentrate
• Tablets
• Tablets, sustained-release
• Tablets, extended release
Legal status
• Rx only
• Not a controlled drug
FDA-approved indications
• Major depressive disorder
• Obsessive-compulsive disorder
• Panic attacks
• Post-traumatic stress disorder
• Social anxiety (social phobia)
• Premenstrual dysphoric disorder
• Seasonal affective disorder
• Smoking cessation
"Off-label" uses
• Postpartum depression (PPD)
Sertraline is used as active as well as preventive treatment for postpartum depression. Women with a history of postpartum depression episodes can be prescribed sertraline immediately after birth to reduce the risk of postpartum depression recurrence4.
Bupropion represents an effective and well-tolerated option for the acute treatment of postpartum depression5
• Binge eating disorder 7
Both drugs reduce anxious-depressive symptoms and binge frequency in persons with binge eating. Bupropion works better for reducing weight and improving sexual performance than sertraline.
• "Winter" depression (Seasonal affective disorder) • ADHD
• Weight loss
• SSRIs-induced sexual dysfunction
• Depression associated with bipolar disorder
Mechanism of action
• Selectively inhibit reabsorption (reuptake) of neurotransmitter serotonin in the brain.
• Sertraline has mild dopamine stimulating effects, and increases neurotransmission of dopamine.
• Enhances neurotransmission via inhibition of norepinephrine and dopamine reuptake.
• No appreciable serotonergic activity.
• 26 hours • 8-24 hours (immediate-release)
• 21 +/- 7 hours (extended-release)
Oral bioavailability
• 20-36% • 5% to 20%
Metabolism, Elimination
• Sertraline undergoes extensive hepatic metabolism by CYP enzymes. The drug is primarily metabolized by CYP3A4 to its active metabolite N-desmethylsertraline and several other metabolites.
• Excretion: urine 51-60%, feces 24-32%.
• Bupropion is extensively metabolized via CYP2B6.
• Three active metabolites: hydroxybupropion, threohydrobupropion and erythrohydrobupropion.
• Excretion: urine 87%, feces 10%.
• Use of MAO inhibitors
• Hypersensitivity to sertraline
• Concomitant use with pimozide
• Hypersensitivity to bupropion
• History of anorexia or bulimia
• Seizure disorder
• Abrupt discontinuation of alcohol or sedatives (including benzodiazepines)
Side effects
Sexual performance
Bupropion is relatively free of sexual side effects. About 60% of men and 40% of women who take sertraline develop sexual problems 16, 21. Bupropion SR represents a more appropriate antidepressant choice than sertraline in patients for whom sexual side effects are a concern.
• Nausea, diarrhea, insomnia, and somnolence occurs significantly more with sertraline treatment than with bupropion SR16, 21
• Dry mouth occurs more frequently with bupropion SR than with sertraline16, 21
• Tremor
• Indigestion
• Decreased appetite
• Excessive sweating
• Ejaculation problems
• Decreased libido
• Headache
• Headache
• Anorexia
• Weight loss
• Agitation
• Dizziness
• Constipation
• Anxiety
• Tinnitus
• Tremor
• Nervousness


Sertraline vs Bupropion for Anxiety

None of Wellbutrin® formulations are licensed for anxiety disorders. Zoloft® is indicated for several anxiety disorders, including panic attacks, social anxiety, obsessive-compulsive disorder. However, both antidepressants have anxiolytic activity.

Sertraline provides more benefits in the treatment of in the treatment of depression with high levels of anxiety (anxious depression) than bupropion6. Enhancement of serotonin neurotransmission by sertraline may explain its more beneficial results.

Bupropion SR and sertraline produce comparable antidepressant and anti-anxiety effects and have equally rapid onset of symptom improvement in patients who suffer from both anxiety and depressive symptoms 22.

Results of retrospective analysis of the effects of bupropion SR and sertraline on anxiety in patients with recurrent major depressive disorder 22. Bupropion SR Sertraline
Effectiveness in reducing depressive symptoms
Effect on anxiety symptoms
Median time to reach a clinically significant anxiolytic effect 4 weeks 4 weeks
Somnolence   more common

Sertraline vs Bupropion for Depression

Bupropion SR and sertraline are similarly effective in the treatment of depression 16, 21.

Results of double-blind comparison of bupropion SR and sertraline in depression 21. Bupropion SR Sertraline
Orgasm dysfunction, nausea, diarrhea, somnolence, and sweating   more frequently

Results of placebo-controlled comparison of bupropion SR and sertraline 16. Bupropion SR Sertraline
Efficacy measures
similar improvements
Orgasm dysfunction   significantly more patients
Headache 30-40% 30-40%
Nausea 18% 31%
Diarrhea 7% 26%
Insomnia 13% 18%
Somnolence 3% 17%
Dry mouth 19% 14%
Decrease in mean body weight -1.06 kg -1.06 kg

Further reading


  • 1. O'Connor CM, Glassman AH, Harrison DJ. Pharmacoeconomic analysis of sertraline treatment of depression in patients with unstable angina or a recent myocardial infarction. J Clin Psychiatry. 2005 Mar;66(3):346-52
  • 2. Thase ME, Haight BR, Johnson MC, Hunt T, Krishen A, Fleck RJ, Modell JG. A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension. J ClinPsychopharmacol. 2008 Jun;28(3):302-7.
  • 3. Lanza di Scalea T, Wisner KL. Antidepressant medication use during breastfeeding. ClinObstet Gynecol. 2009 Sep;52(3):483-97.
  • 4. Kim DR, Epperson CN, Weiss AR, Wisner KL. Pharmacotherapy of postpartum depression. Expert Opin Pharmacother. 2014 Jun;15(9):1223-34.
  • 5. Nonacs RM, Soares CN, Viguera AC, Pearson K, Poitras JR, Cohen LS. Bupropion SR for the treatment of postpartum depression: a pilot study. Int J Neuropsychopharmacol. 2005 Sep;8(3):445-9.
  • 6. Papakostas GI, Stahl SM, Krishen A, Seifert CA, Tucker VL, Goodale EP, Fava M. Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression). J Clin Psychiatry. 2008 Aug;69(8):1287-92.
  • 7. Calandra C, Russo RG, Luca M. Bupropion versus sertraline in the treatment of depressive patients with binge eating disorder: retrospective cohort study. Psychiatr Q. 2012 Jun;83(2):177-85
  • 16. Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther. 1999 Apr;21(4):643-58. PubMed
  • 21. Kavoussi RJ, Segraves RT, Hughes AR, Ascher JA, Johnston JA. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. J Clin Psychiatry. 1997 Dec;58(12):532-7. PubMed
  • 22. Trivedi MH, Rush AJ, Carmody TJ, Donahue RM, Bolden-Watson C, Houser TL, Metz A. Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? J Clin Psychiatry. 2001 Oct;62(10):776-81. PubMed

Published: March 31, 2008
Last reviewed: January 22, 2018


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