Lexapro

Escitalopram (also known under various trade names such as Lexapro (AU, HK, IE, MX, NZ, PH, SG, US), Cipralex(CA, IL, RU, ZA, UK)) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children over 12 years of age withmajor 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.^[1]

Medical uses[edit]

Escitalopram has FDA approval for the treatment of major depressive disorder and generalized anxiety disorderin adults.^[2] 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.

Depression[edit]

Escitalopram was approved by regulatory authorities for the treatment of major depressive disorder on the basis of four placebo controlled, multi-center, double-blind clinical trials, three of which demonstrated a statistical superiority to placebo.^[3] 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.^[4][5][6][7]

In contrast to these findings, a 2011 review concluded that all second generation antidepressants are equally effective,^[8] and treatment guidelines issued by the National Institute of Health and Clinical Excellence and by the American Pyschiatric Association generally reflect this viewpoint.^[9][10]

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.

Anxiety disorder[edit]

There may be a significant improvement in GAD symptoms as early as the first week and the majority of patients respond by week eight with a significant improvement in functioning.^[11][12] It also seems effective in the long-term with relapse on escitalopram (20%) less than placebo (50%).^[13]

Escitalopram and citalopram appear equally effective in panic disorder.^[14]

Other[edit]

Escitalopram as well as other SSRIs are effective in reducing the symptoms of premenstrual syndrome, whether taken in the luteal phase only or continuously.^[15] There is no good data available for escitalopram for seasonal affective disorder as of 2011.^[16]

Adverse effects[edit]

Escitalopram, like other SSRIs, has been shown to affect sexual functions causing side effects such as decreased libido, delayed ejaculation, genital anesthesia,^[17] and anorgasmia.^[18][19]

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.^[20][21][22] Similarly, the UK MHRA data indicate an 80% increase of suicide-related events, not reaching statistical significance, in the escitalopram vs. placebo patients.^[23] 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.^[24] A singlecase report described a patient developing suicidal ideations after beginning treated with escitalopram, and suicidal ideation disappearing after stopping the treatment.^[25]

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).^[26] 1.4–1.8 kg mean weight gain was reported in 8-month trials of escitalopram for depression,^[27] and generalized anxiety disorder.^[28] A 52-week trial of escitalopram for the long-term treatment of depression in elderly also found insignificant 0.6 kg mean weight gain.^[29] Escitalopram may help reduce weight in those treated for binge eating associated obesity.^[30]

Citalopram and escitalopram are associated with dose-dependent QT interval prolongation^[31] and should not be used in those with congenital long QT syndrome or known pre-existing QT interval prolongation, or in combination with other medicines that prolong the QT interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be corrected before starting treatment. For citalopram, new restrictions on the maximum daily doses now apply: 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment. For escitalopram, the maximum daily dose for patients older than 65 years is now reduced to 10 mg/day; other doses remain unchanged.^[32][33]

Escitalopram should be taken with caution when using Saint John's wort.^[34] 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.^[35] Caution should be used when taking cough medicine containing dextromethorphan (DXM) as serotonin syndrome, liver damage, and other negative side effects have been reported.