Escitalopram

Escitalopram is approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder in adolescents and adults, and generalized anxiety disorder (GAD) in adults, in dosage from 5 to 20mg. In European countries including the United Kingdom, it is approved for depression and anxiety disorders; these include: generalized anxiety disorder, social anxiety disorder (SAD), obsessive–compulsive disorder (OCD), and panic disorder with or without agoraphobia. In Australia it is approved for major depressive disorder.{{cite journal|title=Escitalopram oxalate|url=https://www.nps.org.au/australian-prescriber/articles/escitalopram-oxalate|language=en|doi=10.18773/austprescr.2003.107|volume=26|year=2003|journal=Australian Prescriber|pages=146–151|doi-access=free|access-date=15 March 2020|archive-date=10 June 2020|archive-url=https://web.archive.org/web/20200610103705/https://www.nps.org.au/australian-prescriber/articles/escitalopram-oxalate|url-status=live}}{{cite news|url=https://www.reuters.com/article/lundbeck-idUSDKT00159920070112|title=Lundbeck's Cipralex gets EU ok for OCD treatment|date=12 January 2007|work=Reuters|access-date=15 March 2020|language=en|archive-date=10 June 2020|archive-url=https://web.archive.org/web/20200610102100/https://www.reuters.com/article/lundbeck-idUSDKT00159920070112|url-status=live}}{{cite web|url=https://www.medicines.org.uk/emc/product/7718/smpc|title=Cipralex 10 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc)|website=www.medicines.org.uk|access-date=15 March 2020|archive-date=10 June 2020|archive-url=https://web.archive.org/web/20200610102137/https://www.medicines.org.uk/emc/product/7718/smpc|url-status=live}}

Escitalopram is among the most effective and well-tolerated antidepressants for the short-term treatment of major depressive disorder in adults.{{cite journal |date=3 April 2018 |title=The most effective antidepressants for adults revealed in major review |url=https://evidence.nihr.ac.uk/alert/the-most-effective-antidepressants-for-adults-revealed-in-major-review |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/signal-00580}}{{cite journal | vauthors = 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 | title = 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 | journal = Lancet | volume = 391 | issue = 10128 | pages = 1357–1366 | date = April 2018 | pmid = 29477251 | pmc = 5889788 | doi = 10.1016/S0140-6736(17)32802-7 }} It also seems to be the safest one to give to children and adolescents.{{cite journal |date=1 September 2020 |title=Psychiatric drugs given to children and adolescents have been ranked in order of safety | journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/alert_40795|s2cid=241309451 }}{{cite journal | vauthors = Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU | title = Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects | journal = World Psychiatry | volume = 19 | issue = 2 | pages = 214–232 | date = June 2020 | pmid = 32394557 | pmc = 7215080 | doi = 10.1002/wps.20765 }}

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 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.{{cite journal | vauthors = Ramsberg J, Asseburg C, Henriksson M | title = Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e42003 | year = 2012 | pmid = 22876296 | pmc = 3410906 | doi = 10.1371/journal.pone.0042003 | doi-access = free | bibcode = 2012PLoSO...742003R }}{{cite journal | vauthors = Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, Churchill R, Watanabe N, Barbui C | title = Citalopram versus other anti-depressive agents for depression | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 7 | pages = CD006534 | date = July 2012 | pmid = 22786497 | pmc = 4204633 | doi = 10.1002/14651858.CD006534.pub2 }}{{cite journal | vauthors = Favré P | title = [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram] | language = fr | journal = L'Encéphale | volume = 38 | issue = 1 | pages = 86–96 | date = February 2012 | pmid = 22381728 | doi = 10.1016/j.encep.2011.11.003 | trans-title = Clinical efficacy and achievement of a complete remission in depression: Increasing interest in treatment with escitalopram }}{{cite journal | vauthors = Sicras-Mainar A, Navarro-Artieda R, Blanca-Tamayo M, Gimeno-de la Fuente V, Salvatella-Pasant J | title = Comparison of escitalopram vs. citalopram and venlafaxine in the treatment of major depression in Spain: clinical and economic consequences | journal = Current Medical Research and Opinion | volume = 26 | issue = 12 | pages = 2757–2764 | date = December 2010 | pmid = 21034375 | doi = 10.1185/03007995.2010.529430 | s2cid = 43179425 }}

Escitalopram appears to be effective in treating generalized anxiety disorder, with relapse on escitalopram at 20% rather than placebo at 50%, which translates to a number needed to treat of 3.33.{{cite journal | vauthors = Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N | title = Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis | language = English | journal = Lancet | volume = 393 | issue = 10173 | pages = 768–777 | date = February 2019 | pmid = 30712879 | doi = 10.1016/S0140-6736(18)31793-8 | s2cid = 72332967 | url = https://discovery.ucl.ac.uk/id/eprint/10070219/ }}{{cite journal | vauthors = Bech P, Lönn SL, Overø KF | title = 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 | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 2 | pages = 121–129 | date = February 2010 | pmid = 19961809 | doi = 10.4088/JCP.08m04749blu }} Escitalopram appears effective in treating social anxiety disorder as well.{{cite journal | vauthors = Baldwin DS, Asakura S, Koyama T, Hayano T, Hagino A, Reines E, Larsen K | title = Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo | journal = European Neuropsychopharmacology | volume = 26 | issue = 6 | pages = 1062–1069 | date = June 2016 | pmid = 26971233 | doi = 10.1016/j.euroneuro.2016.02.013 | doi-access = free }}

Escitalopram may reduce premenstrual symptoms in women with premenstrual syndrome and premenstrual dysphoric disorder. It seems to be more effective when taken continuously compared to luteal phase administration.{{cite journal |vauthors=Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB |date=August 2024 |title=Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder |url=https://www.ncbi.nlm.nih.gov/pubmed/39140320 |journal=The Cochrane Database of Systematic Reviews |volume=2024 |issue=8 |pages=CD001396 |doi=10.1002/14651858.CD001396.pub4 |pmc=11323276 |pmid=39140320 |via=Cochrane}} It is also occasionally prescribed off-label for insomnia secondary to a mental disorder, and vasomotor symptoms (hot flashes) associated with menopause.

Escitalopram has a relatively favorable side effect profile compared to other antidepressants medication. Some of the most common side effect in order of frequency are, headache, nausea, somnolence, insomnia, dry mouth, fatigue, decreased libido, consipation, and flu like symptoms

Similar to other SSRIs, escitalopram has been shown to affect sexual function, causing delayed ejaculation, and anorgasmia.{{cite journal | vauthors = Clayton A, Keller A, McGarvey EL | title = Burden of phase-specific sexual dysfunction with SSRIs | journal = Journal of Affective Disorders | volume = 91 | issue = 1 | pages = 27–32 | date = March 2006 | pmid = 16430968 | doi = 10.1016/j.jad.2005.12.007 }}{{cite web |url= https://www.allergan.com/Assets/PDF/Lexapro_pi.pdf|title=Lexapro prescribing information|access-date=23 August 2017| archive-date=15 August 2018| archive-url= https://web.archive.org/web/20180815200647/https://www.allergan.com/assets/pdf/lexapro_pi.pdf|url-status=live}}

There is also evidence that SSRIs are correlated with an increase in suicidal 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 of suicidality among the adults treated with escitalopram for psychiatric indications.{{cite web| vauthors =Levenson M, Holland C| title =Antidepressants and Suicidality in Adults: Statistical Evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006)| website =Food and Drug Administration| access-date =13 May 2007| url = https://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4272s1-04-FDA.ppt| archive-date =27 September 2007| archive-url = https://web.archive.org/web/20070927214932/https://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4272s1-04-FDA.ppt| url-status =live}}{{cite web | url = https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf | title = Clinical Review: Relationship Between Antidepressant Drugs and Suicidality in Adults | access-date = 22 September 2007 | vauthors = Stone MB, Jones ML | date = 17 November 2006 | website = Overview for 13 December Meeting of Pharmacological Drugs Advisory Committee (PDAC) | publisher = FDA | pages = 11–74 | archive-date = 16 March 2007 | archive-url = https://web.archive.org/web/20070316092329/https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf | url-status = live }}{{cite web | url = https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf | title = Statistical Evaluation of Suicidality in Adults Treated with Antidepressants | access-date = 22 September 2007 | vauthors = Levenson M, Holland C | date = 17 November 2006 | website = Overview for 13 December Meeting of Pharmacological Drugs Advisory Committee (PDAC) | publisher = FDA | pages = 75–140 | archive-date = 16 March 2007 | archive-url = https://web.archive.org/web/20070316092329/https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf | url-status = live }} 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.{{cite journal | vauthors = Khan A, Schwartz K | title = 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 | journal = Annals of Clinical Psychiatry | volume = 19 | issue = 1 | pages = 31–36 | year = 2007 | pmid = 17453659 | doi = 10.1080/10401230601163550 }}

Citalopram and escitalopram are associated with a mild dose-dependent QT interval prolongation,{{cite journal | vauthors = Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Erb JL, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH | title = QT interval and antidepressant use: a cross sectional study of electronic health records | journal = BMJ | volume = 346 | pages = f288 | date = January 2013 | pmid = 23360890 | pmc = 3558546 | doi = 10.1136/bmj.f288 }} which is a measure of how rapidly the heart muscle repolarizes after each heartbeat. Prolongation of the QT interval is a risk factor for torsades 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{{cite journal | vauthors = Lam RW | title = Antidepressants and QTc prolongation | journal = Journal of Psychiatry & Neuroscience | volume = 38 | issue = 2 | pages = E5–E6 | date = March 2013 | pmid = 23422053 | pmc = 3581598 | doi = 10.1503/jpn.120256 | quote = "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." }} 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/day moxifloxacin (a positive 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.{{cite web |author1=US FDA |title=FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-revised-recommendations-celexa-citalopram-hydrobromide-related |publisher=US FDA |access-date=1 May 2024 |date=15 December 2017}} A QTc increase of less than 60 ms is not likely to confer significant risk. The 30 mg/day escitalopram dose induced significantly less QTc prolongation than a therapeutically equivalent 60 mg/day dose of citalopram, which increased the QTc interval by 18.5 ms.

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).{{cite journal | vauthors = Danielsson B, Collin J, Nyman A, Bergendal A, Borg N, State M, Bergfeldt L, Fastbom J | title = Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study | journal = BMJ Open | volume = 10 | issue = 3 | pages = e034560 | date = March 2020 | pmid = 32169926 | pmc = 7069257 | doi = 10.1136/bmjopen-2019-034560 | ref = sweden-2020 }} Of the 9 antidepressants that were used by patients with TdP, escitalopram ranked 7th by TdP incidence in elderly patients (only venlafaxine and amitriptyline 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 popular antiarrhythmic drug in the study was sotalol 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.

Drugs that prolong the QT interval, such as escitalopram, should be used with caution 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.{{cite web | url = http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON137769 | title = Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings | date = December 2011 | publisher = Medicines and Healthcare products Regulatory Agency | access-date = 5 March 2013 | archive-date = 6 March 2013 | archive-url = https://web.archive.org/web/20130306065253/http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON137769 | url-status = live }}{{cite journal |vauthors=van Gorp F, Whyte IM, Isbister GK |date=September 2009 |title=Clinical and ECG effects of escitalopram overdose |journal=Annals of Emergency Medicine |volume=54 |issue=3 |pages=404–408 |doi=10.1016/j.annemergmed.2009.04.016 |pmid=19556032}} The US Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessor citalopram.{{cite journal | vauthors = Hasnain M, Howland RH, Vieweg WV | title = Escitalopram and QTc prolongation | journal = Journal of Psychiatry & Neuroscience | volume = 38 | issue = 4 | pages = E11 | date = July 2013 | pmid = 23791140 | pmc = 3692726 | doi = 10.1503/jpn.130055 }}

Like other SSRIs, escitalopram has also been reported to cause hyponatremia (low sodium levels), with rates ranging from 0.5 to 32%, which can often be attributed to SIADH.{{cite journal | vauthors = Leth-Møller KB, Hansen AH, Torstensson M, Andersen SE, Ødum L, Gislasson G, Torp-Pedersen C, Holm EA | title = Antidepressants and the risk of hyponatremia: a Danish register-based population study | journal = BMJ Open | volume = 6 | issue = 5 | pages = e011200 | date = May 2016 | pmid = 27194321 | pmc = 4874104 | doi = 10.1136/bmjopen-2016-011200 }} This is typically not dose-dependent and at higher risk for occurrence within the first few weeks of starting treatment.{{cite journal | vauthors = Naschitz JE | title = Escitalopram Dose-Dependent Hyponatremia | journal = Journal of Clinical Pharmacology | volume = 58 | issue = 6 | pages = 834–835 | date = June 2018 | pmid = 29878443 | doi = 10.1002/jcph.1091 }}

Like other SSRIs, escitalopram often exacerbates symptoms of mania and hypomania in individuals misdiagnosed with a depressive disorder instead of a bipolar disorder, making it crucial for clinicians to rule out bipolar disorders before prescribing escitalopram.

Very common effects (>10% incidence) include:{{cite web |title=Lexapro (escitalopram) dosing, indications, interactions, adverse effects, and more |url=https://reference.medscape.com/drug/lexapro-escitalopram-342961 |url-status=live |archive-url=https://web.archive.org/web/20131202233318/http://reference.medscape.com/drug/lexapro-escitalopram-342961#showall |archive-date=2 December 2013 |access-date=9 April 2025 |work=Medscape}}{{cite web| title= Cipralex 5, 10 and 20 mg film-coated tablets - Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|date=2 October 2013|access-date=27 November 2013| url=http://www.medicines.org.uk/emc/medicine/27012/SPC/Cipralex+5%2c+10+and+20+mg+film-coated+tablets/| archive-date=3 December 2013| archive-url= https://web.archive.org/web/20131203010421/http://www.medicines.org.uk/emc/medicine/27012/SPC/Cipralex+5%2c+10+and+20+mg+film-coated+tablets/| url-status=live}}{{cite web|title=Escitalopram-Lupin Tablets (LUPIN AUSTRALIA PTY. LTD)|work=TGA eBusiness Services|publisher=Lupin Australia Pty Ltd|date=21 December 2011|access-date=27 November 2013| url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-01532-3|format=PDF|archive-date=29 March 2019|archive-url=https://web.archive.org/web/20190329053352/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-01532-3|url-status=live}}{{cite journal | vauthors = Mancano MA | title = Unequal Sized Pupils Due to Escitalopram; Adverse Events to Dietary Supplements Causing Emergency Department Visits; Compulsive Masturbation Due to Pramipexole; Metformin-Induced Lactic Acidosis Masquerading As an Acute Myocardial Infarction | journal = Hospital Pharmacy | volume = 51 | issue = 5 | pages = 358–361 | date = May 2016 | pmid = 27303087 | pmc = 4896342 | doi = 10.1310/hpj5105-358 | publisher = Thomas Land Publishers, Inc. }}

• Headache (24%)
• Nausea (18%)
• Ejaculation disorder (9–14%)
• Somnolence (4–13%)
• Insomnia (7–12%)

Common effects (1–10% incidence) include:

{{div col|colwidth=}}

• Abnormal dreams
• Anisocoria
• Anorgasmia
• Anxiety
• Arthralgia (joint pain)
• Constipation
• Decreased or increased appetite
• Diarrhea
• Dilated pupils
• Dizziness
• Dry mouth
• Excessive sweating
• Fatigue
• Fever
• Impotence (erectile dysfunction)
• Libido changes
• Myalgia (muscular aches and pains)
• Paraesthesia (abnormal skin sensation)
• Restlessness
• Sinusitis (nasal congestion)
• Tremor
• Vomiting
• Yawning

{{div col end}}

The most common effect is fatigue or somnolence, particularly in older adults,{{cite journal | vauthors = Lenze EJ |date=20 May 2009 |title=Escitalopram Treatment of Generalized Anxiety Disorder in Older Adults—Reply |journal=JAMA |volume=301 |issue=19 |page=1987 |doi=10.1001/jama.2009.652 |issn=0098-7484}} although patients with pre-existing daytime sleepiness and fatigue may experience paradoxical improvement of these symptoms.{{cite journal | vauthors = Shen J, Hossain N, Streiner DL, Ravindran AV, Wang X, Deb P, Huang X, Sun F, Shapiro CM | title = Excessive daytime sleepiness and fatigue in depressed patients and therapeutic response of a sedating antidepressant | journal = Journal of Affective Disorders | volume = 134 | issue = 1–3 | pages = 421–426 | date = November 2011 | pmid = 21616541 | doi = 10.1016/j.jad.2011.04.047 }}

Escitalopram has not been shown to affect serial reaction time, logical reasoning, serial subtraction, multitasking, or Mackworth Clock task performance.{{cite journal | vauthors = Rosekind MR, Gregory KB, Mallis MM | title = Alertness management in aviation operations: enhancing performance and sleep | journal = Aviation, Space, and Environmental Medicine | volume = 77 | issue = 12 | pages = 1256–1265 | date = December 2006 | pmid = 17183922 | doi = 10.3357/asem.1879.2006 }}

Some people experience persistent sexual side effects when taking SSRIs or after discontinuing them.{{cite book|title=Diagnostic and Statistical Manual of Mental Disorders| author = American Psychiatric Association |publisher=American Psychiatric Publishing |year=2013 |isbn=9780890425558 |edition=5th |location=Arlington, VA |pages=[https://archive.org/details/diagnosticstatis0005unse/page/449 446–449] }} Symptoms of medication-induced sexual dysfunction from antidepressants include difficulty with orgasm, erection, or ejaculation. 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.{{cite journal | vauthors = Bala A, Nguyen HM, Hellstrom WJ | title = Post-SSRI Sexual Dysfunction: A Literature Review | journal = Sexual Medicine Reviews | volume = 6 | issue = 1 | pages = 29–34 | date = January 2018 | pmid = 28778697 | doi = 10.1016/j.sxmr.2017.07.002 }}

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 lower Apgar scores (by <0.4 points). Antidepressant exposure is not associated with an increased risk of spontaneous abortion.{{cite journal | vauthors = Ross LE, Grigoriadis S, Mamisashvili L, Vonderporten EH, Roerecke M, Rehm J, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A | title = Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis | journal = JAMA Psychiatry | volume = 70 | issue = 4 | pages = 436–443 | date = April 2013 | pmid = 23446732 | doi = 10.1001/jamapsychiatry.2013.684 | s2cid = 2065578 | doi-access = }} There is a tentative association of SSRI use during pregnancy with heart problems in the baby. The advantages of their use during pregnancy may thus not outweigh the possible negative effects on the baby.{{cite journal | vauthors = Gentile S | title = Early pregnancy exposure to selective serotonin reuptake inhibitors, risks of major structural malformations, and hypothesized teratogenic mechanisms | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 11 | issue = 10 | pages = 1585–1597 | date = 1 July 2015 | pmid = 26135630 | doi = 10.1517/17425255.2015.1063614 | s2cid = 43329515 }}

{{Main|Antidepressant discontinuation syndrome}}

Escitalopram discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as "electric shock" sensations,{{cite journal |vauthors=Prakash O, Dhar V |date=June 2008 |title=Emergence of electric shock-like sensations on escitalopram discontinuation |journal=Journal of Clinical Psychopharmacology |volume=28 |issue=3 |pages=359–360 |doi=10.1097/JCP.0b013e3181727534 |pmid=18480703}} colloquially called "brain shivers" or "brain zaps" by those affected. Frequent symptoms in one study were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). Very slow tapering is recommended.{{cite journal |vauthors=Yasui-Furukori N, Hashimoto K, Tsuchimine S, Tomita T, Sugawara N, Ishioka M, Nakamura K |date=June 2016 |title=Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study |journal=Clinical Neuropharmacology |volume=39 |issue=3 |pages=125–127 |doi=10.1097/WNF.0000000000000139 |pmid=27171568 |s2cid=45460237}} 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, and hypomania. Other symptoms such as panic attacks, hostility, aggression, impulsivity, akathisia (psychomotor restlessness), mania, worsening of depression, and suicidal ideation can emerge when the dose is adjusted down.{{cite web |title=Lexapro (Escitalopram Oxalate) Drug Information: Warnings and Precautions - Prescribing Information at RxList |url=http://www.rxlist.com/cgi/generic/lexapro_wcp.htm |url-status=dead |archive-url=https://web.archive.org/web/20080616071244/http://www.rxlist.com/cgi/generic/lexapro_wcp.htm |archive-date=16 June 2008 |access-date=9 August 2015}}

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. 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 giving Activated charcoal or giving benzodiazepines for seizures.{{Cite web |first=FDA |title=Lexapro prescribing guide |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021323s055,021365s039lbl.pdf}} Because of the risk of arrhythmias (which may be delayed) prolonged cardiac monitoring is strongly recommended

Escitalopram weakly inhibits CYP2D6, and hence may increase plasma levels of some CYP2D6 substrates such as aripiprazole, risperidone, tramadol, codeine, etc. As escitalopram is only a weak inhibitor of CYP2D6, analgesia from tramadol may not be affected.{{cite journal | vauthors = Noehr-Jensen L, Zwisler ST, Larsen F, Sindrup SH, Damkier P, Brosen K | title = Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain | journal = Clinical Pharmacology and Therapeutics | volume = 86 | issue = 6 | pages = 626–633 | date = December 2009 | pmid = 19710642 | doi = 10.1038/clpt.2009.154 | s2cid = 29063004 }} Escitalopram (at the maximum dose of 20{{nbsp}}mg/day) has been found to increase peak levels of the CYP2D6 substrate desipramine by 40% and total exposure by 100%. Likewise, it has been found to increase peak levels of the CYP2D6 substrate metoprolol by 50% and overall exposure by 82%. Escitalopram does not inhibit CYP3A4, CYP1A2, CYP2C9, CYP2C19, or CYP2E1.

Exposure to escitalopram is increased moderately, by about 50%, when it is taken with omeprazole, a CYP2C19 inhibitor. The authors of this study suggested that this increase is unlikely to be of clinical concern.{{cite journal | vauthors = Malling D, Poulsen MN, Søgaard B | title = The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects | journal = British Journal of Clinical Pharmacology | volume = 60 | issue = 3 | pages = 287–290 | date = September 2005 | pmid = 16120067 | pmc = 1884771 | doi = 10.1111/j.1365-2125.2005.02423.x }} Combination of citalopram with fluoxetine or fluvoxamine resulted in increased exposure to the escitalopram enantiomer, owing to the strong inhibition of CYP2C19 and CYP2D6 by these agents. 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|2018|April|lc=y}} the interaction with escitalopram had not been studied, but some monographs warned of the potential interaction.{{cite web|title=Drug interactions between bupropion and Lexapro|url=https://www.drugs.com/drug-interactions/bupropion-with-lexapro-440-0-1013-565.html?professional=1|website=Drugs.com|access-date=22 April 2018|archive-date=23 April 2018|archive-url=https://web.archive.org/web/20180423033440/https://www.drugs.com/drug-interactions/bupropion-with-lexapro-440-0-1013-565.html?professional=1|url-status=live}} Citalopram did not affect the pharmacokinetics of bupropion or its metabolites in the study.

Escitalopram should be taken with caution when using St. John's wort, ginseng, dextromethorphan (DXM), linezolid, tramadol, and other serotonergic drugs due to the risk of serotonin syndrome.{{cite book|title=2006 Lippincott's Nursing Drug Guide| vauthors = Karch A |publisher=Lippincott Williams & Wilkins|year=2006|isbn=978-1-58255-436-5|location=Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo}}{{cite journal | vauthors = Boyer EW, Shannon M | title = The serotonin syndrome | journal = The New England Journal of Medicine | volume = 352 | issue = 11 | pages = 1112–1120 | date = March 2005 | pmid = 15784664 | doi = 10.1056/NEJMra041867 }} As an SSRI, escitalopram should not be given concurrently with MAOIs.

Escitalopram, similarly to other SSRIs, may increase bleeding risk with NSAIDs (ibuprofen, naproxen, mefenamic acid), antiplatelet drugs, anticoagulants, omega-3 fatty acids, vitamin E, and garlic supplements due to escitalopram's inhibitory effects on platelet aggregation via blocking serotonin transporters on platelets.{{cite web |title=UpToDate |url=https://www.uptodate.com/content-not-available |access-date=10 August 2022 |website=www.uptodate.com |archive-date=9 August 2022 |archive-url=https://web.archive.org/web/20220809223839/https://www.uptodate.com/content-not-available |url-status=live }}

Escitalopram can also prolong the QT interval, and hence it is not recommended in patients who are concurrently on other medications that also can prolong the QT interval. These drugs include antiarrhythmics, antipsychotics, tricyclic antidepressants, some antihistamines (astemizole, mizolastine), macrolide and fluoroquinolone antibiotics, some 5-HT₃ receptor antagonists (except palonosetron), and some antiretrovirals (ritonavir, saquinavir, lopinavir).

Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron. Over time, this leads to a downregulation of pre-synaptic 5-HT_1A receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic factor, which may contribute to a reduction in negative affective biases.{{cite journal | vauthors = Carhart-Harris RL, Nutt DJ | title = Serotonin and brain function: a tale of two receptors | journal = Journal of Psychopharmacology | volume = 31 | issue = 9 | pages = 1091–1120 | date = September 2017 | pmid = 28858536 | pmc = 5606297 | doi = 10.1177/0269881117725915 }}{{cite journal | vauthors = Harmer CJ, Duman RS, Cowen PJ | title = How do antidepressants work? New perspectives for refining future treatment approaches | language = English | journal = The Lancet. Psychiatry | volume = 4 | issue = 5 | pages = 409–418 | date = May 2017 | pmid = 28153641 | pmc = 5410405 | doi = 10.1016/S2215-0366(17)30015-9 }}

Of the SSRIs currently available, 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.Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010. In addition to its antagonist action at the orthosteric site of SERT, escitalopram also binds to an allosteric site on the transporter, thereby decreasing its disassociation rate.{{cite journal | vauthors = Zhong H, Haddjeri N, Sánchez C | title = Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter--a review of current understanding of its mechanism of action | journal = Psychopharmacology | volume = 219 | issue = 1 | pages = 1–13 | date = January 2012 | pmid = 21901317 | doi = 10.1007/s00213-011-2463-5 }} Escitalopram binds to this allosteric site at a greater affinity than other SSRIs.{{cite journal | vauthors = Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N | title = Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies | journal = The International Journal of Neuropsychopharmacology | volume = 10 | issue = 1 | pages = 31–40 | date = February 2007 | pmid = 16448580 | doi = 10.1017/S1461145705006462 | url = https://hal.science/hal-03893598 }} The clinical relevance of this action is unknown.

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.{{cite journal | vauthors = O'Brien FE, O'Connor RM, Clarke G, Dinan TG, Griffin BT, Cryan JF | title = P-glycoprotein inhibition increases the brain distribution and antidepressant-like activity of escitalopram in rodents | journal = Neuropsychopharmacology | volume = 38 | issue = 11 | pages = 2209–2219 | date = October 2013 | pmid = 23670590 | pmc = 3773671 | doi = 10.1038/npp.2013.120 }}

Escitalopram is the (S)-enantiomer (left-handed version) of the racemate citalopram, which is responsible for its name: escitalopram. {{cite book |title=Meyler's Side Effects of Drugs |date=2016 |publisher=Elsevier |page=383 |edition=6 |chapter=Citalopram and escitalopram}}

Image:Cipralex.jpg.]]

Escitalopram was developed in cooperation between Lundbeck and Forest 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.{{cite web | title=2000 Annual Report. p 28 and 33 | url=http://www.materials.lundbeck.com/lundbeck/82/fullpdf/1.pdf | year=2000 | publisher=Lundbeck | access-date=7 April 2007 | archive-date=27 September 2007 | archive-url=https://web.archive.org/web/20070927215329/http://www.materials.lundbeck.com/lundbeck/82/fullpdf/1.pdf | url-status=live }}

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.{{cite web | url = https://www.drugs.com/international/escitalopram.html | work = Drugs.com International | title = Escitalopram | archive-url = https://web.archive.org/web/20200619204531/https://www.drugs.com/international/escitalopram.html | archive-date=19 June 2020 | access-date = 25 April 2015 }}{{cite web | url = https://www.gdziepolek.pl/produkty/50443/mozarin-tabletki-powlekane/zamienniki | work = Gdziepolek.pl | title = Mozarin, zamienniki i podobne rodukty | archive-url = https://web.archive.org/web/20201017185633/https://www.gdziepolek.pl/produkty/50443/mozarin-tabletki-powlekane/zamienniki | archive-date=17 October 2020 | access-date = 17 October 2020 | language = Polish }}

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 by Teva.{{cite web | vauthors = Miranda H | title = FDA OKs Generic Depression Drug – Generic Version of Lexapro Gets Green Light | url = http://www.webmd.com/content/article/122/114778.htm | website = WebMD | access-date = 10 October 2007 | archive-date = 5 January 2007 | archive-url = https://web.archive.org/web/20070105232212/http://www.webmd.com/content/article/122/114778.htm | url-status = live }} In July 2006, the U.S. District Court of Delaware decided in favor of Lundbeck regarding a patent infringement dispute and ruled the patent on escitalopram valid.{{cite news |vauthors=Laforte ME |title=US court upholds Lexapro patent |date=14 July 2006 |url=http://www.firstwordplus.com/Fws.do?articleid=7474B41ED0D14C20894E262219E24B62 |publisher=FirstWord |access-date=10 October 2007 |archive-date=30 October 2021 |archive-url=https://web.archive.org/web/20211030132727/http://www.firstwordplus.com/Fws.do?articleid=7474B41ED0D14C20894E262219E24B62 |url-status=live }}

In 2006, Forest Laboratories was granted an 828-day (2 years and 3 months) extension on its US patent for escitalopram.{{cite press release| title = Forest Laboratories Receives Patent Term Extension for Lexapro| publisher = PRNewswire-FirstCall| date = 2 March 2006| url = http://www.frx.com/news/PressRelease.aspx?ID=824655| access-date = 19 January 2009| archive-date = 15 April 2009| archive-url = https://web.archive.org/web/20090415161937/http://www.frx.com/news/PressRelease.aspx?ID=824655| url-status = live}} 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.{{cite web | vauthors = Frankel A | date = 27 February 2009 | url = http://www.law.com/jsp/article.jsp?id=1202428657301 | title = Forest Laboratories: A Tale of Two Whistleblowers | archive-url = https://web.archive.org/web/20090228182230/http://www.law.com/jsp/article.jsp?id=1202428657301 | archive-date=28 February 2009 | work = The American Lawyer }} 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; paid kickbacks 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.{{cite web | url = http://amlawdaily.typepad.com/forestfca.pdf | title = United States of America v. Forest Laboratories | archive-url = https://web.archive.org/web/20090311044425/http://amlawdaily.typepad.com/forestfca.pdf | archive-date=11 March 2009 | work = US District Court for the district of Massachusetts }}{{cite web | url = https://www.nytimes.com/2009/02/26/business/26drug.html | title = Drug Maker Is Accused of Fraud | archive-url = https://web.archive.org/web/20201111221358/http://www.nytimes.com/2009/02/26/business/26drug.html | archive-date=11 November 2020 | vauthors = Meier B, Carey B | work = The New York Times | date = 25 February 2009 }} Forest denied the allegations{{cite web | url = http://www.frx.com/news/PressRelease.aspx?ID=1260234 | title = Forest Laboratories, Inc. Provides Statement in Response to Complaint Filed by U.S. Government | archive-url = https://archive.today/20130124030551/http://www.frx.com/news/PressRelease.aspx?ID=1260234 | archive-date=24 January 2013 | work = Forest press-release | date = 26 February 2009 }} but ultimately agreed to settle with the plaintiffs for over $313 million.{{cite web|url=https://www.justice.gov/opa/pr/drug-maker-forest-pleads-guilty-pay-more-313-million-resolve-criminal-charges-and-false|title=Drug Maker Forest Pleads Guilty; To Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations|website=www.justice.gov|date=15 September 2010|access-date=22 November 2020|archive-date=30 November 2020|archive-url=https://web.archive.org/web/20201130151443/https://www.justice.gov/opa/pr/drug-maker-forest-pleads-guilty-pay-more-313-million-resolve-criminal-charges-and-false|url-status=live}}

• List of antidepressants

{{Reflist}}

• {{cite web | vauthors = Harris G | title=A Peek at How Forest Laboratories Pushed Lexapro | website=The New York Times | date=1 September 2009 | url= https://www.nytimes.com/2009/09/02/business/02drug.html }}

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