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Lexapro |
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Escitalopram (Lexapro by Forest Laboratories in the United States and elsewhere by Lundbeck as Cipralex and Sipralexa Seroplex)
is an antidepressant of the selective serotonin reuptake inhibitor
(SSRI) class. It is approved for the treatment of major depressive
disorder and generalized anxiety disorder; other indications include
social anxiety disorder, panic disorder and obsessive-compulsive
disorder. Escitalopram is the S-stereoisomer (enantiomer) of the
earlier Lundbeck drug citalopram (Celexa), hence the name escitalopram.
Escitalopram is noted for its high selectivity of serotonin reuptake
inhibition and, as a result has fewer side effects not related to its
serotonergic activity. Pharmacology Escitalopram acts by increasing intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the neuron. Of the SSRIs currently on the market escitalopram has the highest affinity for the human serotonin transporter (SERT). Remarkably, another enantiomer of citalopram (R-citalopram) counteracts to a certain degree the serotonin-enhancing action of escitalopram. As a result, escitalopram is a more potent antidepressant than citalopram, which is a mixture of escitalopram and R-citalopram. In order to explain this phenomenon, researchers from Lundbeck proposed that escitalopram enhances its own binding via an additional interaction with another allosteric site on the transporter. Further research by the same group showed that R-citalopram also enhances binding of escitalopram, and therefore the allosteric interaction cannot explain the observed counteracting effect. However, in the most recent paper the same authors again reversed their findings and reported that R-citalopram decreases binding of escitalopram to the transporter. Although allosteric binding of escitalopram to the serotonin transporter is of unquestionable research interest, its clinical relevance is unclear since the binding of escitalopram to the allosteric site is at least 1000 times weaker than to the primary binding site. In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. Side effects and drug interactions The side effect profile of escitalopram is close to that of other SSRIs, with nausea, somnolence, and gastrointestinal side effects reported as relatively common. Escitalopram, like other SSRIs, has been shown to cause sexual side effects in many patients. Escitalopram is not associated with significant weight gain. For example, 0.6 kg mean weight change after 6 months of treatment with escitalopram for depression was insignificant and similar to that with placebo (0.2 kg). 1.4-1.8 kg mean weight gain was reported in 8-month trials of escitalopram for depression, and generalized anxiety disorder. A 52-week trial of escitalopram for the long-term treatment of depression in elderly also found insignificant 0.6 kg mean weight gain. Escitalopram may help reduce weight in those treated for binge eating associated obesity. It may also cause dizziness after exercise in children. A meta-analysis of clinical trials database conducted by the escitalopram manufacturer Lundbeck found no indication that escitalopram would provoke suicidal behaviour compared with placebo in patients with major depressive disorder and anxiety disorders, on the contrary, suicidal thoughts in the escitalopram group were significantly decreased. An analysis conducted by the FDA found a statistically insignificant 1.5 to 2.4-fold, depending on the statistical technique used, increase of suicidality among the adults treated with escitalopram for psychiatric indications. Similarly, the UK MHRA data indicate an 80% increase of suicide-related events, not reaching statistical significance, in the escitalopram vs placebo patients. The authors of a related study note the general problem with statistical approaches-due to the rarity of suicidal events in clinical trials, it is hard to draw firm conclusions with a sample smaller than two million patients. A single case report described a patient developing suicidal ideation after beginning treatment with escitalopram, and suicidal ideation disappearing after stopping the treatment. Escitalopram should be taken with caution when using St John's wort. Discontinuation symptoms Lexapro discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as paresthesia (for example, electric shock sensations also known as "brain shivers" or "brain zaps"), dizziness and irritability. |
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