Tracks information on drugs on worldwide basis by Dr Anthony Melvin Crasto, helping millions with websites, 9 million hits on google, 2.5 lakh connections worldwide, P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
There is some controversy over selective publishing of SSRI clinical trials. A meta-analysis analyzing published as well as unpublished trials found placebos to be similarly effective to SSRIs in treating mild depression, although SSRIs were more effective than placebo in more severe cases, with the magnitude of SSRI superiority increasing with increasing depression severity.
A series of randomized, double-blind trials have found Escitalopram to be more efficacious and have fewer adverse effects than Citalopram. Meta-analysis show a “small” but statistically significant improvement in effect strength  and some dispute these findings.
Cipralex brand escitalopram 10mg package and tablet sheet
Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron. Of the SSRIs currently on the market, escitalopram has the highest affinity for the human serotonin transporter (SERT). The enantiomer of escitalopram ((R)-citalopram) counteracts to a certain degree the serotonin-enhancing action of escitalopram. As a result, escitalopram has been claimed to be a more potent antidepressant than citalopram, which is a mixture of escitalopram and (R)-citalopram. In order to explain this phenomenon, researchers from Lundbeck proposed that escitalopram enhances its own binding via an additional interaction with another allosteric site on the transporter. Further research by the same group showed that (R)-citalopram also enhances binding of escitalopram, and therefore the allosteric interaction cannot explain the observed counteracting effect. In the most recent paper, however, the same authors again reversed their findings and reported that R-citalopram decreases binding of escitalopram to the transporter. Although allosteric binding of escitalopram to the serotonin transporter is of unquestionable research interest, its clinical relevance is unclear since the binding of escitalopram to the allosteric site is at least 1000 times weaker than to the primary binding site.
In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. The resulting metabolites, desmethylescitalopram and didesmethylescitalopram, are significantly less active and their contribution to the overall action of escitalopram is negligible.
Escitalopram was developed in close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the U.S. FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology. The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram can be considered an example of “evergreening“ (also called “lifecycle management”)– the long-term strategy pharmaceutical companies use in order to extend the lifetime of a drug, in this case of the citalopram franchise. Escitalopram is an enantiopure compound of theracemic mixturecitalopram, used for the same indication, and for that reason it required less investment and less time to develop. Two years after escitalopram’s launch, when the patent on citalopram expired, the escitalopram sales successfully made up for the loss. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.On July 14 of that year, however, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.
In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its US patent for escitalopram. This pushed the patent expiration date from December 7, 2009 to September 14, 2011. Together with the 6-month pediatric exclusivity, the final expiration date was March 14, 2012.
Escitalopram is sold under the following brand names:
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^ Stein, DJ; Andersen, EW; Tonnoir, B; Fineberg, N (2007). “Escitalopram in obsessive-compulsive disorder: A randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study”. Current medical research and opinion23 (4): 701–11. doi:10.1185/030079907X178838. PMID17407626.
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^ Cipriani, A; Furukawa TA; Salanti G; Geddes JR; Higgins JP; Churchill R; Watanabe N; Nakagawa A; Omori IM; McGuire H; Tansella M; Barbui C (2009 February 28). “Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis”. Lancet373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID19185342.
^ Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J (January 2010). “Antidepressant drug effects and depression severity: a patient-level meta-analysis”. JAMA303 (1): 47–53. doi:10.1001/jama.2009.1943.PMID20051569.
^ Ou, JJ; Xun, GL; Wu, RR; Li, LH; Fang, MS; Zhang, HG; Xie, SP; Shi, JG; Du, B; Yuan, XQ; Zhao, JP (2011 Feb). “Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study.”. Psychopharmacology213 (2-3): 639–46. doi:10.1007/s00213-010-1822-y. PMID20340011. |accessdate= requires |url= (help)
^ Yevtushenko, VY; Belous, AI; Yevtushenko, YG; Gusinin, SE; Buzik, OJ; Agibalova, TV (2007 Nov). “Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients.”. Clinical therapeutics29 (11): 2319–32.PMID18158074.
^ Colonna, L; Andersen, HF; Reines, EH (2005 Oct). “A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder.”. Current medical research and opinion21(10): 1659–68. PMID16238906.
^ Moore, N; Verdoux, H; Fantino, B (2005 May). “Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.”. International clinical psychopharmacology20 (3): 131–7. PMID15812262.
^ Montgomery, Stuart; Hansen, Thomas; Kasper, Siegfried (28 September 2010). “Efficacy of escitalopram compared to citalopram: a meta-analysis”. The International Journal of Neuropsychopharmacology14 (02): 261–268.doi:10.1017/S146114571000115X. PMID20875220.
^ Gorman, JM; Korotzer, A; Su, G (2002 Apr). “Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials.”. CNS spectrums7 (4 Suppl 1): 40–4. PMID15131492.
^ Baldwin DS, Reines EH, Guiton C, Weiller E (2007). “Escitalopram therapy for major depression and anxiety disorders”. Ann Pharmacother41 (10): 1583–92.doi:10.1345/aph.1K089. PMID17848424.
^ Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM (2007). “Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder”. Curr Med Res Opin23 (6): 1303–18.doi:10.1185/030079907X188107. PMID17559729.
^ Davidson JR, Bose A, Wang Q (2005). “Safety and efficacy of escitalopram in the long-term treatment of generalized anxiety disorder”. J Clin Psychiatry66 (11): 1441–6.doi:10.4088/JCP.v66n1115. PMID16420082.
^ Kasper S, Lemming OM, de Swart H (2006). “Escitalopram in the long-term treatment of major depressive disorder in elderly patients”. Neuropsychobiology54 (3): 152–9. doi:10.1159/000098650. PMID17230032.
^ Guerdjikova, AI; McElroy SL, Kotwal R, et al. (January 2008). “High-dose escitalopram in the treatment of binge-eating disorder with obesity: a placebo-controlled monotherapy trial”. Human Psychopharmacology: Clinical and Experimental23 (1): 1–11. doi:10.1002/hup.899. PMID18058852.
^ Khan A, Schwartz K (2007). “Suicide risk and symptom reduction in patients assigned to placebo in duloxetine and escitalopram clinical trials: analysis of the FDA summary basis of approval reports”. Ann Clin Psychiatry19 (1): 31–6.doi:10.1080/10401230601163550. PMID17453659.
^ Budur, Kumar; Hutzler, Jeffrey (June 2004). “Severe suicidal ideation with escitalopram (Lexapro): a case report”. Primary Care Psychiatry9 (2): 67–68.doi:10.1185/135525704125004222.
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^ For an overview of supporting data, see Sánchez C, Bøgesø KP, Ebert B, Reines EH, Braestrup C (2004). “Escitalopram versus citalopram: the surprising role of the R-enantiomer”. Psychopharmacology (Berl.)174 (2): 163–76. doi:10.1007/s00213-004-1865-z. PMID15160261.
^ Chen F, Larsen MB, Sánchez C, Wiborg O (2005). “The (S)-enantiomer of (R,S)-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors”.European Neuropsychopharmacology15 (2): 193–198.doi:10.1016/j.euroneuro.2004.08.008. PMID15695064.
^ Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N (2007). “Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies”. The International Journal of Neuropsychopharmacology10 (1): 31–40. doi:10.1017/S1461145705006462. PMID16448580.