Sertraline (Zoloft) versus ...

Sertraline vs. Amitriptyline

Major depressive disorder
Sertraline and amitriptyline have comparable antidepressant efficacy in the treatment of major depression. Sertraline has been shown a tendency to produce greater improvements on quality of life measures 23, 24.

Side effects and tolerability
Sertraline has more favorable safety profile and is better tolerated than amitriptyline.

Sertraline produces higher rate of gastrointestinal complaints and sexual dysfunction than the amitriptyline. Amitriptyline produces a higher rate of dizziness, anticholinergic, sedative, autonomic and circulatory side effects compared with sertraline25. Sertraline has a considerably less detrimental effect on psychomotor performance and may have a slight activating effect not found with amitriptyline 26.

Amitriptyline therapy is associated with significantly more discontinuations due to treatment-related adverse events, in comparison to sertraline 23, 24.

Sertraline vs. Imipramine

Depression, panic disorder
Both sertraline and imipramine are highly effective treatments for major depressive disorder and panic disorder 27.

Side effects
Sertraline has more favorable side effect profile than Imipramine. Sertraline is significantly better tolerated with significantly fewer discontinuations due to adverse events 1, 27.

Onset of action
The improvement begins more rapid with Imipramine than with Sertraline. But no enduring differences beyond week 8 of treatments 1.

Sertraline vs. Nortriptyline

Sertraline and nortriptyline are equally effective in the treatment of late-life major depression, including those patients presenting with severe depression. However, secondary efficacy (posttreatment measures of cognitive function, memory, and quality of life) may be significantly higher with sertraline treatment. Nortriptyline treatment may be associated with a mildly negative effect on cognition. Sertraline-treated patients may have greater improvement in energy and in most quality-of-life measures. Both drugs have similarly beneficial effects on anxiety and sleep 2.

Side effects
Nortriptyline is associated with a significant higher rate of increase in pulse rate 2.

Onset of action
The time course of antidepressant response is comparable for sertraline and nortriptyline 2.

Sertraline vs. Paroxetine (Paxil)

Panic disorder

Both sertraline and paroxetine are equally effective in panic disorder. However, sertraline is associated with significantly less clinical worsening during taper period than paroxetine 4.

Generalized anxiety disorder

Both paroxetine and sertraline appear similarly effective for the treatment of generalized anxiety disorder 14.


Sertraline is significantly better tolerated. Paroxetine has a higher rate of treatment discontinuation due to adverse events 4.

Side effects

Paroxetine has a significantly higher rate of weight gain 4. Also, paroxetine is associated with higher incidence of sexual side-effects like delay of orgasm or ejaculation and impotence 19.

Discontinuation syndrome

Paroxetine discontinuation is associated with the higher degree of emergence of new somatic and psychological symptoms in patients than sertraline 15.

Drug interactions

Sertraline may have advantages paroxetine in elderly patients because of the comparatively low potential for drug interactions.


Sertraline vs. Bupropion (Wellbutrin)

Bupropion SR and sertraline are similarly well tolerated 16.

Side effects
Nausea, diarrhea, insomnia, and somnolence occurs significantly more with sertraline treatment than with bupropion SR. Dry mouth occurs more frequently with bupropion SR than with sertraline. Both medications are associated with similar decreases in body weight. Sertraline treatment is more often associated with sexual dysfunction compared with bupropion SR 16, 21. Bupropion SR may be a more appropriate antidepressant choice than sertraline in patients for whom sexual dysfunction is a concern.


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

Results of retrospective cohort study of bupropion versus sertraline in depressive patients with binge eating disorder 3. Bupropion Sertraline
Effectiveness in reducing weight and improving sexual performances more effective  
Effectiveness in reducing anxious-depressive symptoms and binge frequency

Anxiety in major depressive disorder

Bupropion SR and sertraline have comparable antidepressant and anxiolytic effects and an equally rapid onset of clinically significant anxiolytic activity 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. Trazodone (Desyrel)


Trazodone and sertraline are equally effective in reducing depressive symptoms and promoting remission, and have similar onset times. Trazodone may be a therapeutic option in the treatment of patients with major depression with prevalent sleep disturbances 5.

Side effects

Adverse drug reactions associated with trazodone are mostly of mild intensity and mainly of the nervous system. Most common side effects with sertraline are gastrointestinal (nausea, diarrhea).

Further reading
  • 1. Mavissakalian MR. Imiprmaine vs. sertraline in panic disorder: 24-week treatment completers. Ann Clin Psychiatry. 2003 Sep-Dec;15(3-4):171-80 PubMed
  • 2. William Bondareff, M.D., Ph.D., Murray Alpert, Ph.D., Arnold J. Friedhoff, M.D., Ellen M. Richter, Ph.D., Cathryn M. Clary, M.D. and Evan Batzar, M.S. Comparison of Sertraline and Nortriptyline in the Treatment of Major Depressive Disorder in Late Life. Am J Psychiatry; May 2000; 157:729-736 Article
  • 3. 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. PubMed
  • 4. Bandelow B, Behnke K, Lenoir S, Hendriks GJ, Alkin T, Goebel C, Clary CM. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry. 2004 Mar;65(3):405-13 PubMed
  • 5. Munizza C, Olivieri L, Di Loreto G, Dionisio P. A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder. Curr Med Res Opin. 2006 Sep;22(9):1703-13. PubMed
  • 14. Ball SG, Kuhn A, Wall D, Shekhar A, Goddard AW. Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline. J Clin Psychiatry. 2005 Jan;66(1):94-9. PubMed
  • 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
  • 18. Meijer WE, Heerdink ER, van Eijk JT, Leufkens HG. Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Pharmacoepidemiol Drug Saf. 2002;11:65562. PubMed
  • 19. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, Carrasco JL, Ciudad J, Daniel E, De la Gandara J, Derecho J, Franco M, Gomez MJ, Macias JA, Martin T, Perez V, Sanchez JM, Sanchez S, Vicens E. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997 Fall;23(3):176-94. PubMed
  • 20. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62 Suppl 3:10-21. 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
  • 23. Moller HJ, Glaser K, Leverkus F, Gobel C. Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression. Pharmacopsychiatry. 2000 Nov;33(6):206-12. PubMed
  • 24. Lydiard RB, Stahl SM, Hertzman M, Harrison WM. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression J Clin Psychiatry. 1997 Nov;58(11):484-91. PubMed
  • 25. Cohn CK, Shrivastava R, Mendels J, Cohn JB, Fabre LF, Claghorn JL, Dessain EC, Itil TM, Lautin A. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. J Clin Psychiatry. 1990 Dec;51 Suppl B:28-33. PubMed
  • 26. Mattila MJ, Saarialho-Kere U, Mattila M. Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry. 1988 Aug;49 Suppl:52-8. PubMed
  • 27. Lepola U, Arato M, Zhu Y, Austin C. Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder. Clin Psychiatry. 2003 Jun;64(6):654-62. PubMed

Published: March 31, 2008
Last reviewed: February 22, 2017


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