eMedExpert Home > Facts > Sertraline (Zoloft)

In early 1970s Pfizer 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, biochemist Kenneth Koe and chemist Willard Welch generated and tested some previously unexplored tametraline derivatives. Welch then prepared stereoisomers of the most promising candidate, which were tested in vivo by animal behavioral scientist Albert Weissman. The most potent and selective (+)-cis-isomer was taken into further development and eventually became sertraline.

The discovery of the sertraline molecule was a fortune. During the development, the scientists had to overcome the initial reluctance of Pfizer bureaucracy to pursue sertraline, because Pfizer was considering licensing an antidepressant candidate from another company.

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

• 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
• multiple sclerosis

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 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.

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 potential for drug interactions at the level of the cytochrome P450 enzyme system 4. So sertraline has advantages over some other SSRIs in elderly patients.
• Minimal anticholinergic activity.
• Does not impair vigilance performance 18.
• Maintenance therapy with sertraline is well tolerated and effective for chronic depression 9.

Disadvantages:

• Highest rate of diarrhea than with other SSRIs 8.

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

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.

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.

• Sertraline (Zoloft) versus other medications

• 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.
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• 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
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• 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.
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• 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
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• 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.
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Published: March 31, 2008
Last updated: April 25, 2011