|Trade names||Cipralex, Lexapro, others|
|Drug class||Selective serotonin reuptake inhibitor|
|Metabolism||Liver, specifically the enzymes CYP3A4 and CYP2C19|
|Elimination half-life||27–32 hours|
|Chemical and physical data|
(414.43 as oxalate)
|3D model (JSmol)|
|(what is this?)|
Escitalopram, sold under the brand names Cipralex and Lexapro among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder or generalized anxiety disorder. It is taken by mouth.
Common side effects include trouble sleeping, nausea, sexual problems, and feeling tired. More serious side effects may include suicide in people under the age of 25. It is unclear if use during pregnancy or breastfeeding is safe. Escitalopram is the (S)-stereoisomer of the earlier medication citalopram, hence the name escitalopram.
Escitalopram was approved for medical use in the United States in 2002. In the United States the wholesale cost is about $2.04 per month as of 2017. In the United Kingdom, as of 2018, non-proprietary escitalopram is around 20 times less costly than the proprietary version. Escitalopram is sometimes replaced by twice the dose of citalopram.
- 1 Medical uses
- 2 Side effects
- 3 Pharmacology
- 4 Interactions
- 5 History
- 6 Society and culture
- 7 References
- 8 External links
Escitalopram has FDA approval for the treatment of major depressive disorder in adolescents and adults, and generalized anxiety disorder in adults. In European countries and Australia, it is approved for depression (MDD) and anxiety disorders, these include: 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 over placebo.
Controversy existed regarding the effectiveness of escitalopram compared to its predecessor citalopram. The importance of this issue followed from the greater cost of escitalopram relative to the generic mixture of isomers of 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. As of 2012, reviews had concluded (with caveats in some cases) that escitalopram is modestly superior to citalopram in efficacy and tolerability.
In contrast to these findings, a 2011 review concluded that all second-generation antidepressants are equally effective, although they may differ in onset and side effects. Treatment guidelines issued by the National Institute of Health and Clinical Excellence and by the American Psychiatric Association generally reflect this viewpoint.
In 2018, a systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed escitalopram to be one of the most effective antidepressants in head-to-head studies.
Escitalopram appears to be effective in treating general anxiety disorder, with relapse on escitalopram (20%) less than placebo (50%).
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 are no good data available for escitalopram as treatment for seasonal affective disorder as of 2011. SSRIs do not appear to be useful for preventing tension headaches or migraines.
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. 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.
Escitalopram is not associated with 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).
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 at 20 mg for adults and 10 mg for those older than 65 years or with liver impairment. There are concerns of higher rates of QT prolongation and torsades de pointes compared to other SSRIs. The U.S. Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessor citalopram.
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.
Some people experience persistent sexual side effects after they stop taking SSRIs. This is known as post-SSRI sexual dysfunction (PSSD). Common symptoms include genital anesthesia, erectile dysfunction, anhedonia, decreased libido, premature ejaculation, vaginal lubrication issues, and nipple insensitivity in women. Rates are unknown, and there is no established treatment.
There is a tentative association of SSRI use during pregnancy with heart problems in the baby. The advantages of their use during pregnancy should thus outweigh the possible negative effects on the baby.
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. Therapeutic blood levels of escitalopram are usually in the range of 20–80 μg/L but 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.
Mechanism of action
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 selectivity for the serotonin transporter (SERT) compared to the norepinephrine transporter (NET), making the side-effect profile relatively mild in comparison to less-selective SSRIs.
Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such as verapamil and quinidine may improve its blood brain barrier penetrability. In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor, its antidepressant-like effects were enhanced.
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 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.
Bupropion has been found to significantly increase citalopram plasma concentration and systemic exposure; as of April 2018 the interaction with escitalopram had not been studied, but professional monographs warned of the potential interaction.
Escitalopram can also prolong the QT interval and hence it is not recommended in patients that are concurrently on other medications that also have the ability to prolong the QT interval. These drugs include antiarrhythmics, antipsychotics, tricyclic antidepressants, some antihistamines (astemizole, mizolastine) and some antiretrovirals (ritonavir, saquinavir, lopinavir). Being a SSRI, escitalopram should not be given concurrently with MAOIs or other serotonergic medications.
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.
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.
Society and culture
Allegations of illegal marketing
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 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 physicians 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." In 2010 Forest Pharmaceuticals Inc., agreed to pay more than $313 million to settle the charges over Lexapro and two other drugs, Levothroid and Celexa.
Escitalopram is sold under many brand names worldwide such as Cipralex and Lexapro.
- drugs.com Drugs.com international: Escitalopram Page accessed April 25, 2015
- "X". The American Society of Health-System Pharmacists. Retrieved 28 December 2017.
- "Escitalopram (Lexapro) Use During Pregnancy". Drugs.com. Retrieved 31 December 2017.
- "NADAC as of 2017-12-27". Centers for Medicare and Medicaid Services. Retrieved 31 December 2017.
- "Escitalopram Medicinal Forms". BNF. 2018. Retrieved 27 September 2018. Link restricted to the UK.
- "Protocol for switching patients from escitalopram to citalopram". NHS. 2015. Retrieved 13 February 2018.
- "www.accessdata.fda.gov" (PDF).
- 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. doi:10.1371/journal.pone.0042003. PMC 3410906. PMID 22876296.
- Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, Churchill R, Watanabe N, Barbui C (July 2012). "Citalopram versus other anti-depressive agents for depression". The Cochrane Database of Systematic Reviews. 7 (7): CD006534. doi:10.1002/14651858.CD006534.pub2. PMC 4204633. PMID 22786497.
- Favré P (February 2012). "[Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram]" [Clinical efficacy and achievement of a complete remission in depression: Increasing interest in treatment with escitalopram]. L'Encephale (in French). 38 (1): 86–96. doi:10.1016/j.encep.2011.11.003. PMID 22381728.
- 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". Current Medical Research and Opinion. 26 (12): 2757–64. doi:10.1185/03007995.2010.529430. PMID 21034375.
- 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 (December 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. doi:10.7326/0003-4819-155-11-201112060-00009. PMID 22147715.
- "CG90 Depression in adults: full guidance".
- Practice Guideline for the Treatment of Patients With Major Depressive Disorder (PDF). APA Practice Guidelines (3rd ed.). 2010.[page needed]
- Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR (April 2018). "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis". Lancet. 391 (10128): 1357–1366. doi:10.1016/S0140-6736(17)32802-7. PMC 5889788. PMID 29477251.
- Bech P, Lönn SL, Overø KF (February 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". The Journal of Clinical Psychiatry. 71 (2): 121–9. doi:10.4088/JCP.08m04749blu. PMID 19961809.
- Baldwin DS, Asakura S, Koyama T, Hayano T, Hagino A, Reines E, Larsen K (June 2016). "Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo". European Neuropsychopharmacology. 26 (6): 1062–9. doi:10.1016/j.euroneuro.2016.02.013. PMID 26971233.
- Marjoribanks J, Brown J, O'Brien PM, Wyatt K (June 2013). "Selective serotonin reuptake inhibitors for premenstrual syndrome". The Cochrane Database of Systematic Reviews (6): CD001396. doi:10.1002/14651858.CD001396.pub3. PMID 23744611.
- Thaler K, Delivuk M, Chapman A, Gaynes BN, Kaminski A, Gartlehner G (December 2011). "Second-generation antidepressants for seasonal affective disorder". The Cochrane Database of Systematic Reviews (12): CD008591. doi:10.1002/14651858.CD008591.pub2. PMID 22161433.
- Banzi R, Cusi C, Randazzo C, Sterzi R, Tedesco D, Moja L (May 2015). "Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults". The Cochrane Database of Systematic Reviews (5): CD011681. doi:10.1002/14651858.CD011681. PMID 25931277.
- Banzi R, Cusi C, Randazzo C, Sterzi R, Tedesco D, Moja L (April 2015). "Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults". The Cochrane Database of Systematic Reviews. 4: CD002919. doi:10.1002/14651858.CD002919.pub3. PMID 25829028.
- Clayton A, Keller A, McGarvey EL (March 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.
- "Lexapro prescribing information" (PDF).
- 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.
- 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". Annals of Clinical Psychiatry. 19 (1): 31–6. doi:10.1080/10401230601163550. PMID 17453659.
- Baldwin DS, Reines EH, Guiton C, Weiller E (October 2007). "Escitalopram therapy for major depression and anxiety disorders". The Annals of Pharmacotherapy. 41 (10): 1583–92. doi:10.1345/aph.1K089. PMID 17848424.
- Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Erb JL, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH (January 2013). "QT interval and antidepressant use: a cross sectional study of electronic health records". BMJ. 346: f288. doi:10.1136/bmj.f288. PMC 3558546. PMID 23360890.
- "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.
- van Gorp F, Whyte IM, Isbister GK (September 2009). "Clinical and ECG effects of escitalopram overdose" (PDF). Annals of Emergency Medicine. 54 (3): 404–8. doi:10.1016/j.annemergmed.2009.04.016. PMID 19556032.
- "Towards better patient care: drugs to avoid in 2017". Retrieved 2018-09-17.
- Drugs To Avoid 2017 PDF Download
- Hasnain M, Howland RH, Vieweg WV (July 2013). "Escitalopram and QTc prolongation". Journal of Psychiatry & Neuroscience. 38 (4): E11. doi:10.1503/jpn.130055. PMC 3692726. PMID 23791140.
- Prakash O, Dhar V (June 2008). "Emergence of electric shock-like sensations on escitalopram discontinuation". Journal of Clinical Psychopharmacology. 28 (3): 359–60. doi:10.1097/JCP.0b013e3181727534. PMID 18480703.
- "Lexapro (Escitalopram Oxalate) Drug Information: Warnings and Precautions - Prescribing Information at RxList". Archived from the original on 2008-06-16. Retrieved 2015-08-09.
- American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. p. 449. ISBN 9780890425558.
- Bala A, Nguyen HM, Hellstrom WJ (January 2018). "Post-SSRI Sexual Dysfunction: A Literature Review". Sexual Medicine Reviews. 6 (1): 29–34. doi:10.1016/j.sxmr.2017.07.002. PMID 28778697.
- Gentile S (1 July 2015). "Early pregnancy exposure to selective serotonin reuptake inhibitors, risks of major structural malformations, and hypothesized teratogenic mechanisms". Expert Opinion on Drug Metabolism & Toxicology. 11 (10): 1585–97. doi:10.1517/17425255.2015.1063614. PMID 26135630.
- van Gorp F, Whyte IM, Isbister GK (September 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.
- Haupt D (October 1996). "Determination of citalopram enantiomers in human plasma by liquid chromatographic separation on a Chiral-AGP column". Journal of Chromatography B. 685 (2): 299–305. doi:10.1016/s0378-4347(96)00177-6. PMID 8953171.
- Baselt RC (2008). Disposition of toxic drugs and chemicals in man (8th ed.). Foster City, Ca: Biomedical Publications. pp. 552–553. ISBN 978-0962652370.
- White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–50. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
- Sanchez C, Reines EH, Montgomery SA (July 2014). "A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?". International Clinical Psychopharmacology. 29 (4): 185–96. doi:10.1097/YIC.0000000000000023. PMC 4047306. PMID 24424469.
- Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
- 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): 2209–19. doi:10.1038/npp.2013.120. PMC 3773671. PMID 23670590.
- Karch, Amy (2006). 2006 Lippincott's Nursing Drug Guide. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins. ISBN 978-1-58255-436-5.
- Malling D, Poulsen MN, Søgaard B (September 2005). "The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects". British Journal of Clinical Pharmacology. 60 (3): 287–90. doi:10.1111/j.1365-2125.2005.02423.x. PMC 1884771. PMID 16120067.
- Noehr-Jensen L, Zwisler ST, Larsen F, Sindrup SH, Damkier P, Brosen K (December 2009). "Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain". Clinical Pharmacology and Therapeutics. 86 (6): 626–33. doi:10.1038/clpt.2009.154. PMID 19710642.
- "Drug interactions between bupropion and Lexapro". Drugs.com. Retrieved 22 April 2018.
- "2000 Annual Report. p 28 and 33" (PDF). Lundbeck. 2000. Retrieved 2007-04-07.
- Hitti M. "FDA OKs Generic Depression Drug – Generic Version of Lexapro Gets Green Light". WebMD. Retrieved 2007-10-10.
- Laforte M (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.
- "Drug Maker Forest Pleads Guilty; To Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations". www.justice.gov.
- Royal Pharmaceutical Society of Great Britain (September 2009). British National Formulary (BNF 58). UK: BMJ Group and RPS Publishing. ISBN 978-0-85369-778-7.
- U.S. National Library of Medicine: Drug Information Portal — Escitalopram
- "A Drug Maker’s Playbook Reveals a Marketing Strategy" article in The New York Times by Gardiner Harris, September 1, 2009