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Escitalopram: A Second-Generation SSRI

Published online by Cambridge University Press:  07 November 2014

Michael J. Owens  and
Jerrold F. Rosenbaum
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Abstract

Serotonin (5-hydroxytryptamine, 5-HT) has long been suspected to play a role in the etiology of depression, and modern neurochemical techniques have confirmed this suspicion. Furthermore, all drugs known to be selective (a relative term) serotonin transporter (SERT) inhibitors are effective antidepressants. Of the selective serotonin reuptake inhibitors (SSRIs) approved in a number of countries for use in depression, panic disorder, and obsessive-compulsive disorder, citalopram is the most selective. Citalopram has been used worldwide to treat an estimated 35 million patients, with an excellent safety record. Citalopram is a racemic drug, and its effects on serotonin transport are thought to reside in the S-enantiomer, known as (S)-citalopram or escitalopram. Escitalopram is the most selective SSRI yet developed. Its receptor binding properties and activity in preclinical animal models of depression predict that escitalopram would be effective in the treatment of depression, with approximately twice the potency of the racemate. The pivotal clinical trials of escitalopram not only support this conclusion, but also suggest escitalopram possesses advantages over citalopram in terms of both efficacy and safety. In conclusion, escitalopram is a promising candidate for use as a first-line antidepressant.

Type
Research Article
Information
CNS Spectrums , Volume 7 , Issue S1: The Biological and Clinical Significance of Single Isomers , April 2002 , pp. 34 - 39
Copyright
Copyright © Cambridge University Press 2002

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References

REFERENCES

1.Kraepelin, E. Über die Beeinflussung einfacher psychischer Vorgänge durch einigeArzneimittel. Jena, Germany: Fischer; 1892.Google Scholar
2.Stanley, M, Virgilio, J, Geishon, S. Tritiated Imipramine binding sites are decreased in the frontal cortex of suicides. Science. 1982;216:1337–1339.CrossRefGoogle ScholarPubMed
3.Perry, EK, Marshall, EF, Blessed, G, Tomlinson, BE, Perry, RH. Decreased imipramine binding in the brains of patients with depressive illness. Br J Psychiatry. 1983;142:188–192.CrossRefGoogle ScholarPubMed
4.Owens, MJ, Nemeroff, CB. The serotonin transporter and depression. Depress Anxiety. 1998;8(suppl 1):5–12.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
5.Lopez, JF, Chalmers, DT, Vázquez, DM, Watson, SJ, Akil, H. Serotonin transporter mRNA in rat brain is regulated by classical antidepressants. Biol Psychiatry. 1994;35:287–290.CrossRefGoogle ScholarPubMed
6.Owens, MJ, Nemeroff, CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clinical Chemistry. 1994;40:288–295.CrossRefGoogle ScholarPubMed
7.Owens, MJ, Ritchie, JC. Clinical neuroehemistry. In: Charney, DS, EJ, Nestler, Bunney, BS, eds. Neurobiology of Mental Illness. New York, NY: Oxford University Press; 1999:132–148.Google Scholar
8.Ellis, PM, Salmond, C. Is platelet imipramine binding reduced in depression? A meta-analysis. Biol Psychiatry. 1994;36:292–299.CrossRefGoogle ScholarPubMed
9.Owens, MJ, Ballenger, CA, Knight, DL, Nemeroff, CB. Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT2A receptor binding after chronic hyper-corticosteronemia, (±)-1-(2,5-dimelhoxy-4-iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat. J Pharmacol Exp Ther. 1996;278:1040–1049.Google ScholarPubMed
10.Robertson, DW, Krushinski, JH, Fuller, RW, Leander, JD. Absolute configurations and pharmacological activities of the optical isomers of fluoxetine, a selective serotonin-uptake inhibitor. J Med Chem. 1988;31:1412–1417.CrossRefGoogle ScholarPubMed
11.Wong, DT, Threlkeld, PG, Robertson, DW. Affinities of fluoxetine, its enantiomers, and other inhibitors of serotonin uptake for subtypes of serotonin receptors. Neuropsychopharmacology. 1991;5:43–47.Google ScholarPubMed
12.Thayer, A. Eli Lilly pulls the plug on Prozac isomer drug. Chem Engin News. 2000;78:8.CrossRefGoogle Scholar
13.Hyttel, J, Bogeso, P, Perregaard, J, Sanchez, C. The pharmacological effect of citalopram resides in the (S)-(+)-enantiomer. J Neural Tramm Gen Sect. 1992;88:157–160.CrossRefGoogle ScholarPubMed
14.Owens, MJ, Knight, BS, Nemeroff, CB. Second generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50:345–350.CrossRefGoogle ScholarPubMed
15.Willner, P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology. 1997;134:319–329.CrossRefGoogle ScholarPubMed
16.Montgomery, SA, Loft, H, Sanchez, C, Reines, EH, Papp, M. Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from rat model. Pharmacol Toxicol. 2001;88:282–286.CrossRefGoogle ScholarPubMed
17.Papp, M, Sanchez, C. Escitalopram: potent and rapid in chronic mild stress model of depression. Poster presented at: Annual Meeting of the New Clinical Drug Evaluation Unit; 05 2001; Phoenix, AZ.Google Scholar
18.Mitchell, PJ, Hogg, S. Behavioural effects of escitalopram predict potent antidepressant activity. Poster presented at: Annual Meeting of the Society of Biological Psychiatry; 05 3-5, 2001; New Orleans, LA.Google Scholar
19.Sanchez, C. Escitalopram has potent anxiolytic effects in rodent anxiety models. Poster presented at: Annual Meeting of the New Clinical Drug Evaluation Unit; 05 2001; Phoenix, AZGoogle Scholar
20.Von Moltke, LL, Greenblatt, DJ, Giancarlo, GM, Granda, BW, Hannatz, JS, Shader, RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-eitalopram. Drug Metab Dipos. 2001;29:1102–1109.Google Scholar
21.Burke, WJ, Gergel, I, Bose, A. Fixed dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63:in press.CrossRefGoogle ScholarPubMed
22.Burke, WJ. Fixed dose study of escitalopram in the treatment of depression. Poster presented at: Annual Meeting of the American Psychiatric Association; 05 5-10, 2001; New Orleans, LA.Google Scholar
23. Data on file, Forest Laboratories.Google Scholar
24.Rosen, RC, Lane, RM, Menza, M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol. 1999;19:67–85.CrossRefGoogle ScholarPubMed