Escitalopram was approved for medical use in the United States in 2002.[8] Escitalopram is rarely replaced by twice the dose ofcitalopram; escitalopram is safer and more effective.[10] It is on theWorld Health Organization's List of Essential Medicines.[11] In 2023, it was the second most prescribed antidepressant and fourteenth most commonly prescribed medication in the United States, with more than 37million prescriptions.[12][13] In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.[14]
Escitalopram is among the most effective and well-tolerated antidepressants for the short-term treatment of major depressive disorder in adults.[19][20] It also seems to be the safest one to give to children and adolescents.[21][22]
Controversy existed regarding the effectiveness of escitalopram compared with 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 ofevergreening. Accordingly, this issue has been examined in at least 10 different systematic reviews and meta analyses. As of 2012[update], reviews had concluded (with caveats in some cases) that escitalopram is modestly superior to citalopram in efficacy and tolerability.[23][24][25][26]
Escitalopram appears to be effective in treating generalized anxiety disorder, with relapse on escitalopram at 20% rather than placebo at 50%, which translates to anumber needed to treat of 3.33.[27][28] Escitalopram appears effective in treating social anxiety disorder as well.[29]
Escitalopram may reduce premenstrual symptoms in women withpremenstrual syndrome andpremenstrual dysphoric disorder. It seems to be more effective when taken continuously compared to luteal phase administration.[30] It is also occasionally prescribedoff-label for insomnia secondary to a mental disorder, andvasomotor symptoms (hot flashes) associated with menopause.[15]
Escitalopram has a relatively favorable side effect profile compared to other antidepressant medications. Some of the most common side effect in order of frequency are, headache, nausea, somnolence, insomnia, dry mouth, fatigue, decreased libido, constipation, and flu-like symptoms[31]
There is also evidence that SSRIs are correlated with an increase insuicidal ideation in certain individuals. An analysis conducted by the FDA found a statistically insignificant 1.5 to 2.4-fold (depending on the statistical technique used) increase ofsuicidality among the adults treated with escitalopram for psychiatric indications.[34][35][36] 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.[37]
Citalopram and escitalopram are associated with a mild dose-dependentQT interval prolongation,[38] which is a measure of how rapidly the heart muscle repolarizes after each heartbeat. Prolongation of the QT interval is a risk factor fortorsades de pointes (TdP), a heart rhythm disturbance that is sometimes fatal. Despite the observed change in the QT interval, the risk of TdP from escitalopram appears to be quite low, and it is similar to other antidepressants that are not known to affect the QT interval. A 2013 review[39] discusses several reasons to be optimistic about the safety of escitalopram. It references a crossover study in which 113 subjects were each given four different treatments in randomized order: placebo, 10 mg/day escitalopram, 30 mg/day escitalopram, or 400 mg/daymoxifloxacin (apositive control known to cause QTc prolongation). At 10 mg/day, escitalopram increased the QTc interval by 4.5 milliseconds (ms). At 30 mg/day, the QTc increased by 10.7 ms.[40] A QTc increase of less than 60 ms is not likely to confer significant risk.[39] The 30 mg/day escitalopram dose induced significantly less QTc prolongation than a therapeutically equivalent 60 mg/day dose ofcitalopram, which increased the QTc interval by 18.5 ms.[39]
More data about the cardiac risk from escitalopram can be found in a large observational study from Sweden that took note of all the medications used by all the patients presenting with TdP, and found the incidence of TdP in escitalopram users to be only 0.7 cases of TdP for every 100,000 patients who took the drug (ages 18-64), and only 4.1 cases of TdP for every 100,000 elderly patients who took the drug (ages 65 and up).[41] Of the 9 antidepressants that were used by patients with TdP, escitalopram ranked 7th by TdP incidence in elderly patients (onlyvenlafaxine andamitriptyline had less risk), and it ranked 5th of 9 by TdP incidence in patients ages 18-64. Antidepressants as a class had a relatively low risk of TdP, and most patients on an antidepressant who experienced TdP were also taking another drug that prolonged QT interval. Specifically, 80% of the escitalopram users who experienced TdP were taking at least one other drug known to cause TdP. For comparison, the most popularantiarrhythmic drug in the study wassotalol with 52,750 users, and sotalol had a TdP incidence of 81.1 cases and 41.2 cases of TdP per 100,000 users in the ≥65 and 18-64-year-old demographics, respectively.[41]
Drugs that prolong the QT interval, such as escitalopram, should be used with caution in those with congenitallong 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 withcardiac disease, andelectrolyte 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 withliver impairment.[42][43] The US Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessorcitalopram.[44]
Like other SSRIs, escitalopram has also been reported to causehyponatremia (low sodium levels), with rates ranging from 0.5 to 32%, which can often be attributed toSIADH.[45] This is typically not dose-dependent and at higher risk for occurrence within the first few weeks of starting treatment.[46]
Like other SSRIs, escitalopram often exacerbates symptoms ofmania andhypomania in individuals misdiagnosed with a depressive disorder instead of abipolar disorder, making it crucial for clinicians to rule out bipolar disorders before prescribing escitalopram.[15]
The most common effect is fatigue or somnolence, particularly in older adults,[50] although patients with pre-existing daytime sleepiness and fatigue may experience paradoxical improvement of these symptoms.[51]
Escitalopram has not been shown to affect serial reaction time, logical reasoning, serial subtraction, multitasking, orMackworth Clock task performance.[52]
Some people experience persistent sexual side effects when taking SSRIs or after discontinuing them.[53] Symptoms of medication-induced sexual dysfunction from antidepressants include difficulty with orgasm, erection, or ejaculation.[53] Other symptoms may be genital anesthesia,anhedonia, decreased libido, vaginal lubrication issues, and nipple insensitivity in women. Rates are unknown, and there is no established treatment.[54]
Antidepressant exposure (including escitalopram) is associated with shorter duration of pregnancy (by three days), increased risk of preterm delivery (by 55%), lower birth weight (by 75 g), and lowerApgar scores (by <0.4 points). Antidepressant exposure is not associated with an increased risk of spontaneous abortion.[55] There is a tentative association of SSRI use during pregnancy with heart problems in the baby.[56] The advantages of their use during pregnancy may thus not outweigh the possible negative effects on the baby.[56]
Escitalopram discontinuation, particularly abruptly, may cause certainwithdrawalsymptoms such as "electric shock" sensations,[57] colloquially called "brain shivers" or "brain zaps" by those affected. Frequent symptoms in one study weredizziness (44%), muscle tension (44%),chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). Very slow tapering is recommended.[58] There have been spontaneous reports of discontinuation of escitalopram and other SSRIs and SNRIs, especially when abrupt, leading to dysphoric mood,irritability, agitation, anxiety, headache,lethargy,emotional lability,insomnia, andhypomania. Other symptoms such aspanic attacks, hostility,aggression,impulsivity,akathisia (psychomotor restlessness),mania, worsening of depression, and suicidal ideation can emerge when the dose is adjusted down.[59]
Excessive doses of escitalopram usually cause relatively minor untoward effects, such as agitation andtachycardia. However,dyskinesia,hypertonia, andclonus may occur in some cases. Severe side effects of escitalopram overdose include seizures (which may be delayed), cardiovascular toxicity including QRS/QTc prolongation which can lead to arrhythmias (Torsades de pointes, ventricular fibrillation, and ventricular tachycardia), hypertension, and serotonin syndrome. Treatment of escitalopram overdoses typically involves supportive care, such as givingActivated charcoal or giving benzodiazepines for seizures.[31] Because of the risk of arrhythmias (which may be delayed) prolonged cardiac monitoring is strongly recommended[31]
Escitalopram weakly inhibitsCYP2D6, and hence may increase plasma levels of some CYP2D6 substrates such asaripiprazole,risperidone,tramadol,codeine, etc.[6] As escitalopram is only a weak inhibitor of CYP2D6, analgesia from tramadol may not be affected.[60] Escitalopram (at the maximum dose of 20mg/day) has been found to increasepeak levels of the CYP2D6 substratedesipramine by 40% and total exposure by 100%.[7] Likewise, it has been found to increase peak levels of the CYP2D6 substratemetoprolol by 50% and overall exposure by 82%.[7] Escitalopram does not inhibitCYP3A4,CYP1A2,CYP2C9,CYP2C19, orCYP2E1.[6][7]
Exposure to escitalopram is increased moderately, by about 50%, when it is taken withomeprazole, a CYP2C19 inhibitor.[6] The authors of this study suggested that this increase is unlikely to be of clinical concern.[61] Combination ofcitalopram withfluoxetine orfluvoxamine resulted in increased exposure to the escitalopram enantiomer, owing to the strong inhibition of CYP2C19 and CYP2D6 by these agents.[7]Bupropion, a known strong CYP2D6 inhibitor, has been found to significantly increase citalopram plasma concentration and systemic exposure (peak levels increased by 30%, total exposure increased by 40%); as of April 2018[update] the interaction with escitalopram had not been studied, but some monographs warned of the potential interaction.[62] Citalopram did not affect the pharmacokinetics of bupropion or its metabolites in the study.[62]
Escitalopram increases intrasynaptic levels of the neurotransmitterserotonin by blocking thereuptake of the neurotransmitter into the presynaptic neuron. Over time, this leads to a downregulation of pre-synaptic5-HT1A receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression ofbrain-derived neurotrophic factor, which may contribute to a reduction in negative affective biases.[69][70]
Of the SSRIs currently available, escitalopram has the highestselectivity for theserotonin transporter (SERT) compared to thenorepinephrine transporter (NET), making the side-effect profile relatively mild in comparison to less-selective SSRIs.[65] In addition to its antagonist action at theorthosteric site of SERT, escitalopram also binds to anallosteric site on the transporter, thereby decreasing its disassociation rate.[71] Escitalopram binds to this allosteric site at a greater affinity than other SSRIs.[72] The clinical relevance of this action is unknown.
Escitalopram is a substrate ofP-glycoprotein and hence P-glycoprotein inhibitors such asverapamil andquinidine may improve its blood-brain barrier penetrability.[73] In a preclinical study in rats combining escitalopram with a P-glycoprotein inhibitor, its antidepressant-like effects were enhanced.[73]
Cipralex brand escitalopram 10 mg package and tablet sheet. It is a reference escitalopram formulation, and was produced byLundbeck.
Escitalopram was developed in cooperation betweenLundbeck andForest Laboratories. Its development was initiated in 1997, and the resulting new drug application was submitted to the US FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous experience of Lundbeck and Forest with citalopram, which has similar pharmacology.[75]
Escitalopram is sold under many brand names worldwide such as Cipralex, Lexapro, Lexam, Mozarin, Aciprex, Depralin, Ecytara, Elicea, Gatosil, Nexpram, Nexito, Nescital, Szetalo, Stalopam, Pramatis, Betesda, Scippa and Rexipra.[1][76]
The FDA issued the approval of escitalopram for major depression in August 2002, and for generalized anxiety disorder in December 2003. In May 2006, the FDA approved a generic version of escitalopram byTeva.[77] In July 2006, theU.S. District Court of Delaware decided in favor of Lundbeck regarding a patent infringement dispute and ruled the patent on escitalopram valid.[78]
In 2006, Forest Laboratories was granted an 828-day (2 years and 3 months) extension on its US patent for escitalopram.[79] This pushed the patent expiration date from 7 December 2009, to 14 September 2011. Together with the 6-month pediatric exclusivity, the final expiration date was 14 March 2012.
In 2004, separate civil suits alleging illegal marketing of citalopram and escitalopram for use by children and teenagers by Forest were initiated by two whistleblowers: a physician named Joseph Piacentile and a Forest salesman named Christopher Gobble.[80] In February 2009, the suits were joined. Eleven states and the District of Columbia filed notices of intent to intervene as plaintiffs in the action.
The suits alleged that Forest illegally engaged in off-label promotion of Lexapro for use in children; hid the results of a study showing lack of effectiveness in children; paidkickbacks to physicians to induce them to prescribe Lexapro to children; and conducted so-called "seeding studies" that were, in reality, marketing efforts to promote the drug's use by doctors.[81][82] Forest denied the allegations[83] but ultimately agreed to settle with the plaintiffs for over $313 million.[84]
^Human Medicines Division (September 2022)."Active substance(s): escitalopram"(PDF).List of nationally authorised medicinal products. European Medicines Agency.Archived(PDF) from the original on 6 September 2022. Retrieved6 September 2022.
^abcdefghiPastoor D, Gobburu J (January 2014). "Clinical pharmacology review of escitalopram for the treatment of depression".Expert Opin Drug Metab Toxicol.10 (1):121–128.doi:10.1517/17425255.2014.863873.PMID24289655.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^"Psychiatric drugs given to children and adolescents have been ranked in order of safety".NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 1 September 2020.doi:10.3310/alert_40795.S2CID241309451.
^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'Encéphale (in French).38 (1):86–96.doi:10.1016/j.encep.2011.11.003.PMID22381728.
^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):2757–2764.doi:10.1185/03007995.2010.529430.PMID21034375.S2CID43179425.
^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):121–129.doi:10.4088/JCP.08m04749blu.PMID19961809.
^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.PMID16430968.
^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):31–36.doi:10.1080/10401230601163550.PMID17453659.
^abcLam RW (March 2013)."Antidepressants and QTc prolongation".Journal of Psychiatry & Neuroscience.38 (2):E5 –E6.doi:10.1503/jpn.120256.PMC3581598.PMID23422053.In summary, the effects of citalopram and other antidepressants in therapeutic doses on QTc are not likely to be of clinical relevance unless other known risk factors are present.
^Lenze EJ (20 May 2009). "Escitalopram Treatment of Generalized Anxiety Disorder in Older Adults—Reply".JAMA.301 (19): 1987.doi:10.1001/jama.2009.652.ISSN0098-7484.
^Shen J, Hossain N, Streiner DL, Ravindran AV, Wang X, Deb P, et al. (November 2011). "Excessive daytime sleepiness and fatigue in depressed patients and therapeutic response of a sedating antidepressant".Journal of Affective Disorders.134 (1–3):421–426.doi:10.1016/j.jad.2011.04.047.PMID21616541.
^Rosekind MR, Gregory KB, Mallis MM (December 2006). "Alertness management in aviation operations: enhancing performance and sleep".Aviation, Space, and Environmental Medicine.77 (12):1256–1265.doi:10.3357/asem.1879.2006 (inactive 18 July 2025).PMID17183922.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
^abAmerican Psychiatric Association (2013).Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. pp. 446–449.ISBN978-0-89042-555-8.
^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.PMID28778697.
^Ross LE, Grigoriadis S, Mamisashvili L, Vonderporten EH, Roerecke M, Rehm J, et al. (April 2013). "Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis".JAMA Psychiatry.70 (4):436–443.doi:10.1001/jamapsychiatry.2013.684.PMID23446732.S2CID2065578.
^abGentile 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):1585–1597.doi:10.1517/17425255.2015.1063614.PMID26135630.S2CID43329515.
^Prakash O, Dhar V (June 2008). "Emergence of electric shock-like sensations on escitalopram discontinuation".Journal of Clinical Psychopharmacology.28 (3):359–360.doi:10.1097/JCP.0b013e3181727534.PMID18480703.
^Yasui-Furukori N, Hashimoto K, Tsuchimine S, Tomita T, Sugawara N, Ishioka M, et al. (June 2016). "Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study".Clinical Neuropharmacology.39 (3):125–127.doi:10.1097/WNF.0000000000000139.PMID27171568.S2CID45460237.
^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):626–633.doi:10.1038/clpt.2009.154.PMID19710642.S2CID29063004.
^Karch A (2006).2006 Lippincott's Nursing Drug Guide. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins.ISBN978-1-58255-436-5.
^Boyer EW, Shannon M (March 2005). "The serotonin syndrome".The New England Journal of Medicine.352 (11):1112–1120.doi:10.1056/NEJMra041867.PMID15784664.
^abBrunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
^"UpToDate".www.uptodate.com.Archived from the original on 9 August 2022. Retrieved10 August 2022.
^Zhong H, Haddjeri N, Sánchez C (January 2012). "Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter--a review of current understanding of its mechanism of action".Psychopharmacology.219 (1):1–13.doi:10.1007/s00213-011-2463-5.PMID21901317.
