Sertraline (Zoloft)

Sertraline in Brief
  • Generic name : Sertraline hydrochloride
  • Brand names: Zoloft, Lustral, Sertranex, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton, Xydep, Serlain, Concorz
  • Therapeutic class: Antidepressant
  • Pharmacologic class: Selective serotonin reuptake inhibitor (SSRI)
  • FDA Approved: 1991
  • Chemical Formula: C17H17Cl2N
  • Pregnancy Category: C
  • Habit forming? No
  • Originally discovered: 1977, Pfizer USA Denmark

History

In early 1970s Pfizer's pharmaceutical chemists produced a new series of psychoactive compounds, of which tametraline looked the most promising 20. However, the development of tametraline was soon stopped because of its stimulative properties.

Several years later, in 1977, scientist Kenneth Koe (biochemist) and Willard Welch (chemist) were able to synthesize and test some previously unexplored tametraline derivatives. Then Willard Welch produced stereoisomers of the most prospective candidate, and they tested in vivo by animal behavioral scientist Albert Weissman. The most potent and selective (+)-cis-isomer was developed further and eventually became sertraline.

The discovery of the sertraline molecule was a fortune. At that time during the development of sertraline Pfizer was considering licensing an antidepressant candidate from another company. And the scientists had to overcome the initial Pfizer's intentions to stop sertraline development.

FDA approved uses
  • Major Depressive Disorder
  • Obsessive-Compulsive Disorder
  • Panic Disorder
  • Posttraumatic Stress Disorder (PTSD)
  • Premenstrual Dysphoric Disorder (PMDD)
  • Social Phobia (social anxiety)

Off-label & Investigational uses
  • seasonal affective disorder (SAD) 6
  • general anxiety disorder 10
  • bulimia nervosa 14
  • binge eating disorder (BED) 19
  • premature ejaculation 2
  • fibromyalgia 13
  • bipolar depression 15
  • autistic spectrum disorders 17
  • neurocardiogenic syncope 3
  • chronic fatigue syndrome 21
  • writer's cramp (case report) 16
  • alcohol dependence 5
  • nocturnal enuresis (bed-wetting) 23
  • impulsive aggressive/ violent behavior25

Seasonal affective disorder (SAD)
A placebo-controlled study has been shown that sertraline is an effective and well-tolerated therapy for SAD. The medication was well tolerated and the most frequent adverse events were nausea, diarrhea, insomnia and dry mouth.

General anxiety disorder
Sertraline appears to be effective and well tolerated in the treatment of generalized anxiety disorder. This medication demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD. Also, study have shown that sertraline may be safe and effective for the treatment of GAD in children and adolescents.

Bulimia nervosa (BN)
Studies show that antidepressants are efficacious in eating disorders. Randomized controlled trial 14 confirms that sertraline is well tolerated and effective in reducing binge-eating crises and purging in patients with BN.

Binge eating disorder
Sertraline may be effective and well tolerated in the treatment of binge eating disorder. Sertraline has been shown to reduce the frequency of binges, clinical global severity, and body mass index.

Premature ejaculation
Sertraline appears to be a useful agent in the treatment of premature ejaculation. Studies have shown that sertraline therapy can cause significant prolongation of time to ejaculation.

Fibromyalgia
Sertraline may help diminish pain, morning stiffness and improve sleep in fibromyalgia.

Chronic fatigue syndrome
One RCT studied sertraline in people with chronic fatigue syndrome.


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Sertraline "pros" and "cons"

Advantages:

  • Appropriate initial choice for people with major depression. Research favours sertraline over other antidepressants in terms of efficacy and acceptability 12.
  • The only SSRI approved for the long-term treatment of PTSD.
  • Lower risk of weight gain than with citalopram, fluvoxamine, and paroxetine 7.
  • Low likelihood of drug interactions at the level of the hepatic cytochrome P450 enzyme system 4. So sertraline has advantages over some other SSRIs in elderly patients and those taking complex multidrug regimens.
  • Minimal anticholinergic activity.
  • Does not impair vigilance performance 18.
  • Maintenance therapy with sertraline is well tolerated and effective for chronic depression 9.
  • The most suitable SSRI for nursing mothers. Mothers taking sertraline have very low levels of sertraline in breastmilk. As a result, sertraline is usually not detected in the serum of the infant 22.
  • The most linear relationship between the dose and plasma level 24.

Disadvantages:

  • Highest rate of diarrhea than with other SSRIs 8.

Time to clear out of the system

Sertraline has half-life of about 26 hr. It may take 5 to 6 days to clear out of the system.

Mechanism of action

Sertraline selectively inhibits the reuptake of serotonin at the presynaptic neuronal membrane, thus increasing the concentration of the serotonin at the synapse and enhancing of serotonergic neuronal transmission. The increased availability of serotonin is considered to improve depression symptoms.

In addition, it has a weak activity in inhibiting the reuptake of dopamine.

Sertraline does not cause significant sedation and does not interfere with psychomotor performance.

Weaning off Sertraline

Sertraline has a half-life of about one day. That means that for every day that passes without taking the medication the level in the blood falls by 50%. After one day the level is reduced to 50% of the original level, after two days to 25%, after three days to 12.5%, and so on. When one stops Zoloft too rapidly a withdrawal syndrome may develop. While most people coming off Zoloft have no withdrawal symptoms, some people do have one or more.

Further reading
References
  • 1. Physicians’ Desk Reference, 59th ed; Thomson PDR: Montvale, NJ; 2005.
  • 2. McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride. Int J Impot Res 1998;10:181-4. PubMed
  • 3. Grubb BP, Samoil D, Kosinski D, Kip K, Brewster P. Use of sertraline hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994;24:490-4.
  • 4. Ereshefsky L, Riesenman C, Lam YW. Clin Pharmacokinet. 1995;29 Suppl 1:10-8.
  • 5. Kranzler HR, Armeli S, Tennen H. Post-treatment outcomes in a double-blind, randomized trial of sertraline for alcohol dependence. Alcohol Clin Exp Res. 2012 Apr PubMed
  • 6. Moscovitch A, Blashko CA, Eagles JM, Darcourt G, Thompson C, Kasper S, Lane RM. A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Psychopharmacology (Berl). 2004 Feb;171(4):390-7. PubMed
  • 7. Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004 Oct;65(10):1365-71. PubMed
  • 8. 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 Saf. 2002;11:655–62. PubMed
  • 9. Keller MB, Kocsis JH, Thase ME, Gelenberg AJ, Rush AJ, Koran L, Schatzberg A, Russell J, Hirschfeld R, Klein D, McCullough JP, Fawcett JA, Kornstein S, LaVange L, Harrison W. Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial. JAMA. 1998 Nov 18;280(19):1665-72.
  • 10. Allgulander C, Dahl AA, Austin C, Morris PL, Sogaard JA, Fayyad R, Kutcher SP, Clary CM. Efficacy of sertraline in a 12-week trial for generalized anxiety disorder. Am J Psychiatry. 2004 Sep;161(9):1642-9.
  • 11. Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. NEJM 2006 Mar 23;354(12):1231-42.
  • 12. Cipriani A, Furukawa TA, Geddes JR, Malvini L, Signoretti A, McGuire H, Churchill R, Nakagawa A, Barbui C. Does randomized evidence support sertraline as first-line antidepressant for adults with acute major depression? J Clin Psychiatry. 2008 Nov;69(11):1732-42 PubMed
  • 13. Gonzalez-Viejo MA, Avellanet M, Hernandez-Morcuende MI. A comparative study of fibromyalgia treatment: ultrasonography and physiotherapy versus sertraline treatment. Ann Readapt Med Phys. 2005 Nov;48(8):610-5. PubMed
  • 14. Milano W, Petrella C, Sabatino C, Capasso A. Treatment of bulimia nervosa with sertraline: a randomized controlled trial. Adv Ther. 2004 Jul-Aug;21(4):232-7. PubMed
  • 15. 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. Br J Psychiatry. 2006 Aug;189:124-31.
  • 16. Isaacs A. Remission of writer's cramp with sertraline. Australas Psychiatry. 2008 Feb;16(1):55.
  • 17. Hellings JA, Kelley LA, Gabrielli WF, Kilgore E, Shah P. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry. 1996 Aug;57(8):333-6. PubMed
  • 18. Riedel WJ, Eikmans K, Heldens A, Schmitt JA. Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment. J Psychopharmacol. 2005 Jan;19(1):12-20.
  • 19. McElroy SL, Casuto LS, Nelson EB, Lake KA, Soutullo CA, Keck PE Jr, Hudson JI. Placebo-controlled trial of sertraline in the treatment of binge eating disorder. Am J Psychiatry. 2000 Jun;157(6):1004-6.
  • 20. Willard M. Welch. Discovery and preclinical development of the serotonin reuptake inhibitor sertraline. Advances in Medicinal Chemistry 1995;113-148.
  • 21. Behan PO, Hannifah H. 5-HT reuptake inhibitors in CFS. J Immunol Immunopharmacology. 1995;15:66–69.
  • 22. Berle JO, Steen VM, Aamo TO, et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes. J Clin Psychiatry. 2004;65:1228-34.
  • 23. Mahdavi-Zafarghandi R, Seyedi A. Treatment of monosymptomatic nocturnal enuresis: sertraline for non-responders to desmopressin. Iran J Med Sci. 2014 Mar;39(2):136-9. PubMed
  • 24. Mugdha E. Thakur, Dan G. Blazer, David C. Steffens. Clinical Manual of Geriatric Psychiatry. American Psychiatric Publishing; 1 Ed. 2013, p.142
  • 25. Kavoussi RJ, Liu J, Coccaro EF. An open trial of sertraline in personality disordered patients with impulsive aggression. J Clin Psychiatry. 1994 Apr;55(4):137-41.

Published: March 31, 2008
Last updated: January 26, 2017

Interesting facts

Sertraline (Zoloft) facts
  • After unsuccessful treatment with an SSRI, approximately 25% of patients have a remission of symptoms after switching to another antidepressant 11.
  • Zoloft may be effective in the treatment of refractory neurocardiogenic syncope in children and adolescents.
  • Sertraline is the only SSRI that noticeably inhibits the reuptake of dopamine. This may explain why it does not raise the serum levels of the hormone prolactin.
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