|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Metabolism||Liver, specifically the enzymes CYP3A4 and CYP2C19|
(414.43 as oxalate)
Escitalopram ( ) also known by the brand names Lexapro and Cipralex among others, 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. Whether escitalopram exhibits superior therapeutic properties to citalopram or merely represents an example of “evergreening” is controversial.
Medical uses 1
- Depression 1.1
- Anxiety disorder 1.2
- Other 1.3
Adverse effects 2
- List of adverse effects 2.1
- Discontinuation symptoms 2.2
- Overdose 2.3
- Drug–food interactions 3.1
- History 4
Society and culture 5
- Allegations of illegal marketing 5.1
- Brand names 5.2
- References 6
- Cited texts 7
- Further reading 8
- External links 9
Escitalopram has FDA approval for the treatment of major depressive disorder in adolescents and adults, and generalized anxiety disorder in adults. 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), and panic disorder with or without agoraphobia.
Escitalopram was approved by regulatory authorities for the treatment of major depressive disorder on the basis of four placebo controlled, double-blind trials, three of which demonstrated a statistical superiority to placebo. Nonetheless, considerable controversy exists regarding the superiority of escitalopram to its predecessor citalopram. The importance of this issue follows from the greater cost of escitalopram relative to the generic mixture of isomers citalopram prior to the expiration of the escitalopram patent in 2012, which led to charges of evergreening. Accordingly, this issue has been examined in at least 10 different systematic reviews and meta analyses. The most recent of these have concluded (with caveats in some cases) that escitalopram is modestly superior to citalopram in efficacy and/or tolerability.
In contrast to these findings, a 2011 review concluded that all second-generation antidepressants are equally effective, and treatment guidelines issued by the National Institute of Health and Clinical Excellence and by the American Psychiatric Association generally reflect this viewpoint.
The utility of antidepressant drugs in the treatment of mild-to-moderate depression is itself controversial. This issue is discussed in detail in the SSRI article.
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. It also seems effective in the long-term with relapse on escitalopram (20%) less than placebo (50%).
Escitalopram and citalopram appear equally effective in panic disorder.
Escitalopram as well as other SSRIs are effective in reducing the symptoms of premenstrual syndrome, whether taken in the luteal phase only or continuously. There is no good data available for escitalopram for seasonal affective disorder as of 2011.
Escitalopram, like other SSRIs, has been shown to affect sexual functions causing side effects such as decreased
- U.S. National Library of Medicine: Drug Information Portal — Escitalopram
- Lexapro (Forest Laboratories) Official Lexapro homepage
- Cipralex (Lundbeck) Official Cipralex homepage
- Pharmacological information Lexapro
- Cipla Medpro Official Cipla Medpro homepage
- "A Drug Maker’s Playbook Reveals a Marketing Strategy" article in The New York Times by Gardiner Harris, September 1, 2009
- Royal Pharmaceutical Society of Great Britain (September 2009). British National Formulary (BNF 58). UK: BMJ Group and RPS Publishing.
- NHS pays millions of pounds more than it needs to for drugs, The Independent. Retrieved 05/10/2011.
- "Escitalopram Oxalate". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
- Ramsberg J, Asseburg C, Henriksson M (2012). "Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model". PLoS ONE 7 (8): e42003.
- Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, Churchill R, Watanabe N, Barbui C (2012). "Citalopram versus other anti-depressive agents for depression". Cochrane Database Syst Rev 7: CD006534.
- Favré P (February 2012). "[Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram]". Encephale (in French) 38 (1): 86–96.
- Sicras-Mainar A, Navarro-Artieda R, Blanca-Tamayo M, Gimeno-de la Fuente V, Salvatella-Pasant J (December 2010). "Comparison of escitalopram vs. citalopram and venlafaxine in the treatment of major depression in Spain: clinical and economic consequences". Curr Med Res Opin 26 (12): 2757–64.
- 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 (Dec 6, 2011). "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.
- "CG90 Depression in adults: full guidance".
- "PsychiatryOnline | APA Practice Guidelines | Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition".
- Davidson JR, Bose A, Korotzer A, Zheng H (2004). "Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study". Depress Anxiety 19 (4): 234–40.
- Bech P, Lönn SL, Overø KF (2010). "Relapse prevention and residual symptoms: a closer analysis of placebo-controlled continuation studies with escitalopram in major depressive disorder, generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder". J Clin Psychiatry 71 (2): 121–9.
- Stahl SM, Gergel I, Li D (2003). "Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial". J Clin Psychiatry 64 (11): 1322–7.
- Marjoribanks J, Brown J, O'Brien PM, Wyatt K (Jun 7, 2013). "Selective serotonin reuptake inhibitors for premenstrual syndrome.". The Cochrane database of systematic reviews 6: CD001396.
- Thaler K, Delivuk M, Chapman A, Gaynes BN, Kaminski A, Gartlehner G (Dec 7, 2011). "Second-generation antidepressants for seasonal affective disorder.". The Cochrane database of systematic reviews (12): CD008591.
- Bolton JM, Sareen J, Reiss JP (2006). "Genital anesthesia persisting six years after sertraline discontinuation". J Sex Marital Ther 32 (4): 327–30.
- Clayton A, Keller A, McGarvey EL (2006). "Burden of phase-specific sexual dysfunction with SSRIs". Journal of Affective Disorders 91 (1): 27–32.
- Lexapro prescribing information
- Levenson M, Holland C. "Antidepressants and Suicidality in Adults: Statistical Evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006)". Retrieved 2007-05-13.
- 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.
- 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.
- 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.
- 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.
- Baldwin DS, Reines EH, Guiton C, Weiller E (2007). "Escitalopram therapy for major depression and anxiety disorders". Ann Pharmacother 41 (10): 1583–92.
- 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.
- 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.
- 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.
- Guerdjikova AI, McElroy SL, Kotwal R, Welge JA, Nelson E, Lake K, Alessio DD, Keck PE, Hudson JI (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.
- Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Erb JL, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH (2013). "QT interval and antidepressant use: a cross sectional study of electronic health records". BMJ 346: f288.
- "Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings".
- van Gorp F, Whyte IM, Isbister GK (2009). "Clinical and ECG Effects of Escitalopram Overdose". Annals of Emergency Medicine 54 (3): 404–8.
- Karch, Amy (2006). 2006 Lippincott's Nursing Drug Guide. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins.
- Malling D, Poulsen MN, 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.
- Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM (2007). "Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects". N. Engl. J. Med. 356 (26): 2684–92.
- "Lexapro (escitalopram) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 27 November 2013.
- "Cipralex 5, 10 and 20 mg film-coated tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. 2 October 2013. Retrieved 27 November 2013.
- "ESCITALOPRAM-LUPIN TABLETS (LUPIN AUSTRALIA PTY. LTD)" (PDF). TGA eBusiness Services. Lupin Australia Pty Ltd. 21 December 2011. Retrieved 27 November 2013.
- "ESCITALOPRAM (escitalopram oxalate) tablet, film coated [Apotex Corp.]". DailyMed. Apotex Corp. September 2013. Retrieved 27 November 2013.
- Prakash O, Dhar V (2008). "Emergence of electric shock-like sensations on escitalopram discontinuation". J Clin Psychopharmacol 28 (3): 359–60.
- "Lexapro – Warnings". RxList. 12/08/2004. Retrieved 2006-10-22.
- van Gorp F, Whyte IM, Isbister GK (2009). "Clinical and ECG effects of escitalopram overdose". Ann Emerg Med 54 (3): 404–8.
- Haupt D (1996). "Determination of citalopram enantiomers in human plasma by liquid chromatographic separation on a Chiral-AGP column". J. Chromatogr. B, Biomed. Appl. 685 (2): 299–305.
- Baselt RC (2008). Disposition of toxic drugs and chemicals in man (8th ed.). Foster City, Ca: Biomedical Publications. pp. 552–553.
- 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.
- 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.
- 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.
- 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.
- 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.
- Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
- "2000 Annual Report. p 28 and 33" (PDF). Lundbeck. 2000. Retrieved 2007-04-07.
- Miranda Hitti. "FDA OKs Generic Depression Drug – Generic Version of Lexapro Gets Green Light". WebMD. Retrieved 2007-10-10.
- Marie-Eve Laforte (2006-07-14). "US court upholds Lexapro patent". FirstWord. Retrieved 2007-10-10.
- "Forest Laboratories Receives Patent Term Extension for Lexapro" (Press release). PRNewswire-FirstCall. 2006-03-02. Retrieved 2009-01-19.
- "Forest Laboratories: A Tale of Two Whistleblowers" article by Alison Frankel in The American Lawyer February 27, 2009
- United States of America v. Forest Laboratories Full text of the federal complaint filed in the US District Court for the district of Massachusetts
- "Drug Maker Is Accused of Fraud" article by Barry Meier and Benedict Carey in The New York Times February 25, 2009
- "Forest Laboratories, Inc. Provides Statement in Response to Complaint Filed by U.S. Government" Forest press-release. February 26, 2009.
- "Pharmaceutical Benefits Scheme (PBS) - Escitalopram". Australian Government.
- Animaxen: Colombia
- Anxipram (GenPharma): India
- Anxiset-E: India
- Cipralex: Canada
- Cipralex (Lundbeck): Greece, Turkey
- Citoles: Turkey
- Citram: Croatia
- Depralin: Poland
- Ecitalex (Andrómaco): Chile
- Ectiban (Laboratorio Chile): Chile
- Ecytara (KRKA): Slovenia
- Elicea (KRKA): Russia, Poland
- Entact: Greece, Italy
- Es-pramcit (NabiQasim): Pakistan
- Escicor: Australia
- Escigress-10 (Stanford Laboratories Pvt. Ltd.): India
- Esciprex: Ireland
- Escital: Nigeria
- Escitalopram Accord: Estonia
- Escitalopram Actavis (Actavis): Finland, Greece
- Escitalopram Generics (Mylan): Greece
- Escitalopram Teva (Teva): Greece, Israel, Sweden
- Escitil (Egis): Czech Republic
- Esertia: Spain
- Esipram: Australia
- Esitalo: Australia
- Eslorex: Turkey
- Esopram Actavis (Actavis): Iceland
- Espran: Canada
- Esto (Unipharm Ltd.): Israel
- Exodus: Brazil
- Ezentius: Uruguay
- Ezopram (Actavis): Ukraine
- Feliz-s: India
- Jovia (United Laboratories): Philippines
- Lata: Serbia
- Lenuxin (Richter Gedeon): Czech Republic, Russia
- Lexam: Australia
- Lexamil: South Africa
- Lexapro (Forest Laboratories): Australia, The Netherlands, United States of America
- Losita (Eskayef Bangladesh): Bangladesh
- Losiram: Turkey
- Loxalate (Alphapharm): Australia, New Zealand
- Miracitol (Orion Corporation): Russia
- Morcet (Searle): Pakistan
- Nexito (Sun Pharmaceutical): India, United States
- Prolide (Teva): Perú
- Reconter: Brazil
- Reposil: Chile
- Secita: Turkey
- Selectra (Actavis): Russia
- Selpram: Pakistan
- Seroplex (Lundbeck): France
- Sipralexa (Lundbeck): Belgium
- Stalopam (Lupin Limited): India
- Tiopram: Turkey
- Zelax: Jordan
Escitalopram is sold under the following brand names:
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. 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. The suits allege that Forest illegally engaged in off-label promoting of Lexapro for use in children, that the company hid the results of a study showing lack of effectiveness in children, and that the company paid kickbacks to doctors to induce them to prescribe Lexapro to children. It was also alleged that the company conducted so-called "seeding studies" that were, in reality, marketing efforts to promote the drug's use by doctors. 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."
Allegations of illegal marketing
Society and culture
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 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. 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.
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,Tramadol, 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.
Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such as verapamil and quinidine may improve its blood-brain penetrability. In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor enhanced its antidepressant-like effects.
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 racemic mixture of the two enantiomers. 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.
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. Escitalopram seems to be less dangerous than citalopram in overdose and comparable to other SSRIs.
Escitalopram discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as "electric shock" sensations (also known as "brain shivers" or "brain zaps"), dizziness, acute depressions and irritability, as well as heightened senses of akathisia.
- Somnolence (sleepiness)
- Decreased appetite
- Increased appetite
- Abnormal dreams
- Libido decreased
- Sinusitis (nasal congestion)
- Dry mouth
- Excessive sweating
- Arthralgia (joint pain)
- Myalgia (muscular aches and pains)
- Pyrexia (fever)
- Ejaculation disorder
- Impotence (erectile dysfunction)
Common (1-10% incidence) adverse effects include:
Very common (>10% incidence) adverse effects include:
List of adverse effects
suggest there may be a when taking escitalopram in the third trimester of pregnancy.
Escitalopram should be taken with caution when using Saint John's wort. Exposure to escitalopram is increased moderately, by about 50%, when it is taken with omeprazole. The authors of this study suggested that this increase is unlikely to be of clinical concern. Caution should be used when taking cough medicine containing dextromethorphan (DXM) as serotonin syndrome, liver damage, and other negative side effects have been reported.
- for citalopram, 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment.
- for escitalopram, 10 mg for patients older than 65 years; other doses remain unchanged.
Citalopram and escitalopram are associated with dose-dependent QT interval prolongation 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. In December 2011, the UK implemented new restrictions on the maximum daily doses:
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). 1.4–1.8 kg mean weight gain was reported in 8-month trials of escitalopram for depression, and generalized anxiety disorder. A 52-week trial of escitalopram for the long-term treatment of depression in elderly also found insignificant 0.6 kg mean weight gain. Escitalopram may help reduce weight in those treated for binge eating associated obesity.
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. Similarly, the UK MHRA data indicate an 80% increase of suicide-related events, not reaching statistical significance, in the escitalopram vs. placebo patients. 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.