Escitalopram

From Wikipedia, the free encyclopedia - View original article

Escitalopram
Systematic (IUPAC) name
(S)-1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
Clinical data
Trade namesLexapro
AHFS/Drugs.commonograph
MedlinePlusa603005
Licence dataUS FDA:link
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability80%
Protein binding~56%
MetabolismLiver, specifically the enzymes CYP3A4 and CYP2C19
Half-life27–32 hours
Identifiers
CAS number128196-01-0 YesY
ATC codeN06AB10
PubChemCID 146570
DrugBankDB01175
ChemSpider129277 YesY
UNII4O4S742ANY YesY
ChEBICHEBI:36791 YesY
ChEMBLCHEMBL1508 YesY
Chemical data
FormulaC20H21FN2O 
Mol. mass324.392 g/mol
(414.43 as oxalate)
 N (what is this?)  (verify)
 
Jump to: navigation, search
Escitalopram
Systematic (IUPAC) name
(S)-1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
Clinical data
Trade namesLexapro
AHFS/Drugs.commonograph
MedlinePlusa603005
Licence dataUS FDA:link
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral
Pharmacokinetic data
Bioavailability80%
Protein binding~56%
MetabolismLiver, specifically the enzymes CYP3A4 and CYP2C19
Half-life27–32 hours
Identifiers
CAS number128196-01-0 YesY
ATC codeN06AB10
PubChemCID 146570
DrugBankDB01175
ChemSpider129277 YesY
UNII4O4S742ANY YesY
ChEBICHEBI:36791 YesY
ChEMBLCHEMBL1508 YesY
Chemical data
FormulaC20H21FN2O 
Mol. mass324.392 g/mol
(414.43 as oxalate)
 N (what is this?)  (verify)

Escitalopram (also known under various trade names such as Lexapro (AU, HK, IE, MX, NZ, PH, SG, US), Cipralex (CA, IL, RU, ZA, UK)) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children over 12 years of age with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Escitalopram is the (S)-stereoisomer (enantiomer) of the earlier Lundbeck drug citalopram, hence the name escitalopram. The similarity between escitalopram and citalopram has led to accusations of "evergreening", an accusation that Lundbeck has rejected.[1]

Independent analysis has found all SSRIs to be more or less equivalent in benefits.[2] When both published and unpublished trials are taken into account the benefit appears to be little to none in those with mild or moderate depression.[3]

Medical uses[edit]

Escitalopram has FDA approval for the treatment of major depressive disorder and generalized anxiety disorder in adults.[4] In European countries, it is approved for depression (MDD) and certain anxiety disorders: general anxiety disorder (GAD), social anxiety disorder (SAD), obsessive compulsive disorder (OCD), panic disorder with or without agoraphobia.

Depression[edit]

There are concerns regarding selective publishing of SSRI clinical trials.[5][6] A meta-analysis which looked at both published and unpublished trials found placebos to be similarly effective to SSRIs in treating mild to moderate depression, although SSRIs were more effective than placebo in more severe cases, with the magnitude of SSRI superiority increasing with increasing depression severity.[3]

A 2011 review concluded that all second generation antidepressants are equally effective[2] and a 2010 review did not find evidence to support escitalopram being better than citalopram.[7]

A 2009 Cochrane review found some evidence favoring escitalopram over the antidepressants citalopram and fluoxetine in the first two weeks of major depression[8] as did another 2009 review.[9] There were however concerns of sponsorship bias and publication bias.[6][8] In another review escitalopram and sertraline had the highest rate of efficacy and acceptability among adults receiving treatment for major depression with second-generation antidepressants, with escitalopram fairing slightly (but not statistically significantly) better than sertraline in both regards.[10] There is no evidence for differential speed of onset of action from SSRIs overall or escitalopram specifically.[11]

Anxiety disorder[edit]

There may be a significant improvement in GAD symptoms as early as the first week and the majority of patients respond by week eight with a significant improvement in functioning.[12][13] It also seems effective in the long-term with relapse on escitalopram (20%) less than placebo (50%).[14]

Escitalopram and citalopram appear equally effective in panic disorder.[15]

Other[edit]

Escitalopram as well as other SSRIs are effective in reducing the symptoms of premenstrual syndrome, whether taken in the luteal phase only or continuously.[16] There is no good data available for escitalopram for seasonal affective disorder as of 2011.[17]

Adverse effects[edit]

Adverse effects by incidence[18][19][20][21]
Very common (>10% incidence) adverse effects include:

Common (1-10% incidence) adverse effects include:

  • Insomnia
  • Somnolence
  • Dizziness
  • Paraesthesia
  • Tremor
  • Decreased appetite
  • Increased appetite
  • Weight gain
  • Anxiety
  • Restlessness
  • Abnormal dreams
  • Libido decreased
  • Anorgasmia
  • Sinusitis
  • Yawning
  • Diarrhoea
  • Constipation
  • Vomiting
  • Dry mouth
  • Excessive sweating
  • Arthralgia (joint pain)
  • Myalgia (muscular aches and pains)

Uncommon (0.1-1% incidence) adverse effects include:

Rare (<0.1% incidence) adverse effects include:

Unknown incidence adverse effects include:

Escitalopram, like other SSRIs, has been shown to affect sexual functions causing side effects such as decreased libido, delayed ejaculation, genital anesthesia,[22] and anorgasmia.[23][24] Although usually reversible upon discontinuation, these sexual side effects can last for months or years or be permanent after the drug has been completely withdrawn.[25] This is known as post SSRI sexual dysfunction.

An analysis conducted by the FDA found a statistically insignificant 1.5 to 2.4-fold (depending on the statistical technique used) increase of suicidality among the adults treated with escitalopram for psychiatric indications.[26][27][28] Similarly, the UK MHRA data indicate an 80% increase of suicide-related events, not reaching statistical significance, in the escitalopram vs. placebo patients.[29] The authors of a related study note the general problem with statistical approaches: due to the rarity of suicidal events in clinical trials, it is hard to draw firm conclusions with a sample smaller than two million patients.[30] A single case report described a patient developing suicidal ideations after beginning treatment with escitalopram, and suicidal ideation disappearing after stopping the treatment.[31]

Escitalopram is not associated with significant weight gain. For example, 0.6 kg mean weight change after 6 months of treatment with escitalopram for depression was insignificant and similar to that with placebo (0.2 kg).[32] 1.4–1.8 kg mean weight gain was reported in 8-month trials of escitalopram for depression,[33] and generalized anxiety disorder.[34] A 52-week trial of escitalopram for the long-term treatment of depression in elderly also found insignificant 0.6 kg mean weight gain.[35] Escitalopram may help reduce weight in those treated for binge eating associated obesity.[36]

Citalopram and escitalopram are associated with dose-dependent QT interval prolongation[37] and should not be used in those with congenital long QT syndrome or known pre-existing QT interval prolongation, or in combination with other medicines that prolong the QT interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be corrected before starting treatment. For citalopram, new restrictions on the maximum daily doses now apply: 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment. For escitalopram, the maximum daily dose for patients older than 65 years is now reduced to 10 mg/day; other doses remain unchanged.[38][39]

Escitalopram should be taken with caution when using Saint John's wort.[40] Exposure to escitalopram is increased moderately, by about 50%, when it is taken with omeprazole. The authors of this study, employed by Lundbeck, suggested that this increase is unlikely to be of clinical concern.[41] Caution should be used when taking cough medicine containing dextromethorphan (DXM) as serotonin syndrome, liver damage, and other negative side effects have been reported.

Discontinuation symptoms[edit]

Escitalopram discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as "electric shock" sensations[42] (also known as "brain shivers" or "brain zaps"), dizziness, acute depressions and irritability, bladder control issues, as well as heightened senses of akathisia.[43]

Human data suggests there's a risk when taking Lexapro in the third trimester of pregnancy.[44]

Overdose[edit]

Excessive doses of escitalopram usually cause relatively minor untoward effects such as agitation and tachycardia. However, dyskinesia, hypertonia and clonus may occur in some cases. Plasma escitalopram concentrations are usually in a range of 20-80 μg/L in therapeutic situations and may reach 80-200 μg/L in the elderly, patients with hepatic dysfunction, those who are poor CYP2C19 metabolizers or following acute overdose. Monitoring of the drug in plasma or serum is generally accomplished using chromatographic methods. Chiral techniques are available to distinguish escitalopram from its racemate, citalopram.[45][46][47] Escitalopram seems to be less dangerous than citalopram in overdose and comparable to other SSRIs.[48]

Drug/Food Interactions[edit]

Escitalopram, similarly to other SSRIs (with the exception of fluvoxamine), inhibits CYP2D6 and hence may increase plasma levels of a number of CYP2D6 substrates such as aripiprazole, risperidone, codeine, etc. Escitalopram can also prolong the QT interval and hence it is not recommended in patients that are concurrently on other medications that have the ability to prolong the QT interval. Being a SSRI escitalopram should not be given concurrently with MAOIs or other serotonergic medications.[49]

Pharmacology[edit]

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.[50] Further research by the same group showed that (R)-citalopram also enhances binding of escitalopram,[51] 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.[52] 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.

Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such as verapamil and quinidine may improve its blood-brain penetrability.[53] In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor enhanced its antidepressant-like effects.[53]

History[edit]

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.[54] 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"[55] (also called "lifecycle management"[56])– 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 the racemic mixture citalopram, 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.[57] 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.[58]

In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its US patent for escitalopram.[59] 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.

Controversy[edit]

According to The New York Times, aggressive pharmaceutical marketing of escitalopram by Forest Laboratories has been controversial: the generic alternatives to the drug are cheaper, but a substantial number of doctors continue to prescribe the more expensive proprietary drug. The United States Senate Special Committee on Aging has released portions of the "Lexapro Fiscal 2004 Marketing Plan" which gives some of the details of the plans to promote use of the drug by doctors.[60][full citation needed][61]

In 2004, two separate civil suits alleging illegal marketing of citalopram and escitalopram for use by children and teenagers by Forest were initiated by two whistleblowers, one by a non-practicing physician named Joseph Piacentile, and the other by a Forest salesman named Christopher Gobble who was disturbed by what he witnessed at Forest.[62]

In February 2009, these two suits received support from the US Attorney for Massachusetts and were combined into one. Eleven states and the District of Columbia have also filed notices of intention to intervene as plaintiffs in the action. At the time, these drugs were approved only for use by adults and the application for use of citalopram in children was specifically rejected by the FDA. Although it is not illegal for physicians to prescribe a medicine for an off-label use not approved by the Food and Drug Administration, it is illegal for a manufacturer to promote the drugs for such uses. The government alleged that a research study showing lack of effectiveness when taken by children was concealed from its own medical advisers and sales personnel, as well as from researchers who conducted a study financed by the company. From 2001 to 2004, Forest heavily promoted results from another clinical trial it had financed which showed the drug was effective. Federal prosecutors also allege that the company has paid kickbacks to doctors to induce them to prescribe the medicines to children. The kickbacks allegedly included baseball tickets, a $1000 certificate to one of the most expensive New York restaurants, and paid vacations. Further, the complaint alleges that in September 2004, a Forest executive testified before Congress: "I want to emphasize that, because the FDA has not approved pediatric labeling of our products, Forest has always been scrupulous about not promoting the pediatric use of our antidepressant drugs, Celexa and Lexapro. That is the law and we follow it." It is also alleged that the company conducted so-called "seeding studies" that were, in reality, marketing efforts to promote the drug's use by doctors.[63][64] Forest responded to these allegations that it "is committed to adhering to the highest ethical and legal standards, and off-label promotion and improper payments to medical providers have consistently been against Forest policy.[65]"

In Britain, the form Cipralex costs £14.91, while Lundbeck's older Cipramil can be found for £1.31. The Independent newspaper reported that this costs Britain's National Health Service (NHS) almost £25m extra per year, with no clear clinical benefits.[1] The Independent also describes the patenting of escitalopram as an example of evergreening — slightly changing a drug that is about to go off-patent in order to acquire a patent for the new version, despite its containing similar ingredients to the previous version.[1] Lundbeck has denied that it has "evergreened" escitalopram.

Brand names[edit]

Escitalopram is sold under the following brand names:

  • Animaxen — Colombia
  • Anxipram (GenPharma) — India
  • Anxiset-E — India
  • Cipralex (Lundbeck)
  • Citalin
  • Citram — Croatia
  • Ecytara (KRKA) — Slovenia
  • Elicea (KRKA) — Russia, Poland
  • Entact — Greece
  • Escital — Nigeria
  • Escitalopram Actavis (Actavis) — Finland
  • Escitil (Egis) — Czech Republic
  • Esertia — Spain
  • Esitalo — Australia
  • Esopram Actavis (Actavis) — Iceland
  • Esto (Unipharm Ltd.) — Israel
  • Escitalopram Teva (Teva) — Israel
  • Exodus — Brazil
  • Ezopram (Actavis) — Ukraine
  • Feliz-s - india
  • Fubianil — Pakistan
  • Lenuxin (Richter Gedeon) — Czech Republic, Russia
  • Lexam

References[edit]

  1. ^ a b c NHS pays millions of pounds more than it needs to for drugs, The Independent. Retrieved 05/10/2011.
  2. ^ a b Gartlehner, G; Hansen, RA; Morgan, LC; Thaler, K; Lux, L; Van Noord, M; Mager, U; Thieda, P; Gaynes, BN; Wilkins, T; Strobelberger, M; Lloyd, S; Reichenpfader, U; Lohr, KN (2011 Dec 6). "Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.". Annals of internal medicine 155 (11): 772–85. PMID 22147715. 
  3. ^ a b 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". JAMA 303 (1): 47–53. doi:10.1001/jama.2009.1943. PMID 20051569. 
  4. ^ "Escitalopram Oxalate". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  5. ^ Ioannidis JP (2008). "Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?". Philos Ethics Humanit Med 3: 14. doi:10.1186/1747-5341-3-14. PMC 2412901. PMID 18505564. 
  6. ^ a b Cipriani, A; Purgato, M; Furukawa, TA; Trespidi, C; Imperadore, G; Signoretti, A; Churchill, R; Watanabe, N; Barbui, C (2012 Jul 11). "Citalopram versus other anti-depressive agents for depression.". The Cochrane database of systematic reviews 7: CD006534. PMID 22786497. 
  7. ^ Trkulja, V (February 2010). "Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials.". Croatian medical journal 51 (1): 61–73. PMID 20162747. 
  8. ^ a b Cipriani, A; Santilli C; Furukawa TA; Signoretti A; Nakagawa A; McGuire H; Churchill R; Barbui C (2009 April 15). "Escitalopram versus other antidepressant agents for depression". In Cipriani, Andrea. Cochrane database of systematic reviews (2): CD006532. doi:10.1002/14651858.CD006532.pub2. PMID 19370639. CD006532. 
  9. ^ Kennedy, SH; Andersen, HF; Thase, ME (January 2009). "Escitalopram in the treatment of major depressive disorder: a meta-analysis.". Current medical research and opinion 25 (1): 161–75. PMID 19210149. 
  10. ^ 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". Lancet 373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342. 
  11. ^ Papakostas et al, J Clin Psychiatry 2007; 68: 1907–12.
  12. ^ Davidson et al, Depress Anxiety 2004; 19: 234–40
  13. ^ Stein et al, Ann Clin Psychiatry 2005; 17: 71–5
  14. ^ Bech et al, J Clin Psychiatry 2010; 71: 121–9
  15. ^ Stahl et al, J Clin Psychiatry 2003; 64:1322–7, MS
  16. ^ Marjoribanks, J; Brown, J; O'Brien, PM; Wyatt, K (2013 Jun 7). "Selective serotonin reuptake inhibitors for premenstrual syndrome.". The Cochrane database of systematic reviews 6: CD001396. PMID 23744611. 
  17. ^ Thaler, K; Delivuk, M; Chapman, A; Gaynes, BN; Kaminski, A; Gartlehner, G (2011 Dec 7). "Second-generation antidepressants for seasonal affective disorder.". The Cochrane database of systematic reviews (12): CD008591. PMID 22161433. 
  18. ^ "Lexapro (escitalopram) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 27 November 2013. 
  19. ^ "Cipralex 5, 10 and 20 mg film-coated tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. 2 October 2013. Retrieved 27 November 2013. 
  20. ^ "ESCITALOPRAM-LUPIN TABLETS (LUPIN AUSTRALIA PTY. LTD)" (PDF). TGA eBusiness Services. Lupin Australia Pty Ltd. 21 December 2011. Retrieved 27 November 2013. 
  21. ^ "ESCITALOPRAM (escitalopram oxalate) tablet, film coated [Apotex Corp.]". DailyMed. Apotex Corp. September 2013. Retrieved 27 November 2013. 
  22. ^ Bolton JM, Sareen J, Reiss JP (2006). "Genital anesthesia persisting six years after sertraline discontinuation". J Sex Marital Ther 32 (4): 327–30. doi:10.1080/00926230600666410. PMID 16709553. 
  23. ^ Clayton A, Keller A, McGarvey EL (2006). "Burden of phase-specific sexual dysfunction with SSRIs". Journal of Affective Disorders 91 (1): 27–32. doi:10.1016/j.jad.2005.12.007. PMID 16430968. 
  24. ^ Lexapro prescribing information
  25. ^ Csoka AB, Bahrick AS, Mehtonen O-P (2008). "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs)". J Sex Med. 5 (1): 227–33. doi:10.1111/j.1743-6109.2007.00630.x. PMID 18173768. 
  26. ^ Levenson M, Holland C. "Antidepressants and Suicidality in Adults: Statistical Evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006)". Retrieved 2007-05-13. 
  27. ^ Stone MB, Jones ML (2006-11-17). "Clinical Review: Relationship Between Antidepressant Drugs and Suicidality in Adults" (PDF). Overview for December 13 Meeting of Pharmacological Drugs Advisory Committee (PDAC). FDA. pp. 11–74. Retrieved 2007-09-22. 
  28. ^ Levenson M; Holland C (2006-11-17). "Statistical Evaluation of Suicidality in Adults Treated with Antidepressants" (PDF). Overview for December 13 Meeting of Pharmacological Drugs Advisory Committee (PDAC). FDA. pp. 75–140. Retrieved 2007-09-22. 
  29. ^ Gunnell D, Saperia J, Ashby D (2005). "Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomized controlled trials submitted to the MHRA's safety review". BMJ 330 (7488): 385. doi:10.1136/bmj.330.7488.385. PMC 549105. PMID 15718537. 
  30. ^ 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 Psychiatry 19 (1): 31–6. doi:10.1080/10401230601163550. PMID 17453659. 
  31. ^ Budur, Kumar; Hutzler, Jeffrey (June 2004). "Severe suicidal ideation with escitalopram (Lexapro): a case report". Primary Care Psychiatry 9 (2): 67–68. doi:10.1185/135525704125004222. 
  32. ^ Baldwin DS, Reines EH, Guiton C, Weiller E (2007). "Escitalopram therapy for major depression and anxiety disorders". Ann Pharmacother 41 (10): 1583–92. doi:10.1345/aph.1K089. PMID 17848424. 
  33. ^ 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 Opin 23 (6): 1303–18. doi:10.1185/030079907X188107. PMID 17559729. 
  34. ^ Davidson JR, Bose A, Wang Q (2005). "Safety and efficacy of escitalopram in the long-term treatment of generalized anxiety disorder". J Clin Psychiatry 66 (11): 1441–6. doi:10.4088/JCP.v66n1115. PMID 16420082. 
  35. ^ Kasper S, Lemming OM, de Swart H (2006). "Escitalopram in the long-term treatment of major depressive disorder in elderly patients". Neuropsychobiology 54 (3): 152–9. doi:10.1159/000098650. PMID 17230032. 
  36. ^ 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 Experimental 23 (1): 1–11. doi:10.1002/hup.899. PMID 18058852. 
  37. ^ Castro V, Clements C, Murphy S “QT interval and antidepressant use: a cross sectional study of electronic health records” BMJ 2013;346:f288
  38. ^ "Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings". Medicines and Healthcare products Regulatory Agency. December 2011. Retrieved March 5, 2013. 
  39. ^ Van Gorp, Freek; Whyte, Ian M.; Isbister, Geoffrey K. (2009). "Clinical and ECG Effects of Escitalopram Overdose". Annals of Emergency Medicine 54 (3): 404–8. doi:10.1016/j.annemergmed.2009.04.016. PMID 19556032. 
  40. ^ Karch, Amy (2006). 2006 Lippincott's Nursing Drug Guide. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins. ISBN 1-58255-436-6. 
  41. ^ Malling, D.; Poulsen, M.; Søgaard, B. (2005). "The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects". British Journal of Clinical Pharmacology 60 (3): 287–290. doi:10.1111/j.1365-2125.2005.02423.x. PMC 1884771. PMID 16120067.  edit
  42. ^ Prakash and Dhar, J Clin Psychopharmacol 2008; 28: 359–60
  43. ^ "Lexapro – Warnings". RxList. 12/08/2004. Retrieved 2006-10-22. 
  44. ^ Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM, for the National Birth Defects Prevention Study. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007;356:2684–92.
  45. ^ van Gorp F, Whyte IM, Isbister GK. Clinical and ECG effects of escitalopram overdose. Ann. Emer. Med. 54: 404-408, 2009.
  46. ^ Haupt D. Determination of citalopram enantiomers in human plasma by liquid chromatographic separation on a Chiral-AGP column. J. Chrom. B 685: 299-305, 1996.
  47. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 552-553.
  48. ^ White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.  edit
  49. ^ Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
  50. ^ 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. PMID 15160261. 
  51. ^ 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 Neuropsychopharmacology 15 (2): 193–198. doi:10.1016/j.euroneuro.2004.08.008. PMID 15695064. 
  52. ^ 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 Neuropsychopharmacology 10 (1): 31–40. doi:10.1017/S1461145705006462. PMID 16448580. 
  53. ^ a b O'Brien, FE; O'Connor, RM; Clarke, G; Dinan, TG; Griffin, BT; Cryan, JF (October 2013). "P-glycoprotein inhibition increases the brain distribution and antidepressant-like activity of escitalopram in rodents". Neuropsychopharmacology 38 (11): 2209–2219. doi:10.1038/npp.2013.120. PMID 23670590. 
  54. ^ "2000 Annual Report. p 28 and 33" (PDF). Lundbeck. 2000. Retrieved 2007-04-07. 
  55. ^ ""New drugs from old". Presented at the Medical Journal Club, Morriston Hospital, by Scott Pegler, pharmacist at the National Health Service, UK, on November 20, 2006." (PPT). Retrieved 2007-04-07. 
  56. ^ "New drugs from old". Drug and Therapeutics Bulletin (BMJ Publishing Group Ltd.) 44 (10): 73–77. 2006. doi:10.1136/dtb.2006.441073. PMID 17067118. 
  57. ^ Miranda Hitti. "FDA OKs Generic Depression Drug – Generic Version of Lexapro Gets Green Light". WebMD. Retrieved 2007-10-10. 
  58. ^ Marie-Eve Laforte (2006-07-14). "US court upholds Lexapro patent". FirstWord. Retrieved 2007-10-10. 
  59. ^ "Forest Laboratories Receives Patent Term Extension for Lexapro" (Press release). PRNewswire-FirstCall. 2006-03-02. Retrieved 2009-01-19. 
  60. ^ Harris, "A Drug Maker’s Playbook Reveals a Marketing Strategy"
  61. ^ Lexapro Fiscal 2004 Marketing Plan
  62. ^ "Forest Laboratories: A Tale of Two Whistleblowers" article by Alison Frankel in The American Lawyer February 27, 2009
  63. ^ United States of America v. Forest Laboratories Full text of the federal complaint filed in the US District Court for the district of Massachusetts
  64. ^ "Drug Maker Is Accused of Fraud" article by Barry Meier and Benedict Carey in The New York Times February 25, 2009
  65. ^ "Forest Laboratories, Inc. Provides Statement in Response to Complaint Filed by U.S. Government" Forest press-release. February 26, 2009.

Cited texts[edit]

External links[edit]