Citalopram (Celexa) and Escitalopram (Lexapro) are selective serotonin reuptake inhibitors (SSRIs) primarily prescribed for major depressive disorder and various anxiety disorders. While chemically similar, they function as distinct clinical entities with differences in potency and safety considerations. Understanding the distinction between the two medications requires examining their molecular structure, which influences their dosing and pharmacological profiles.
Understanding the Molecular Connection
The fundamental difference between Citalopram and Escitalopram lies in their chemical structure, specifically chirality. Citalopram is a racemic mixture, meaning it contains two mirror-image molecules called enantiomers in an equal 50/50 ratio: the R-enantiomer and the S-enantiomer. The therapeutic effect—inhibition of serotonin reuptake—is provided almost entirely by the S-enantiomer.
Escitalopram is a purified compound containing only the active S-enantiomer, denoted by the prefix “es.” The R-enantiomer in Citalopram is not inert; studies suggest it may actively interfere with the S-enantiomer’s therapeutic effect. It interacts with the serotonin transporter protein, reducing the binding affinity of the active S-enantiomer. This antagonism limits Citalopram’s overall potency and may slow the onset of its effects. Escitalopram, as the pure S-enantiomer, avoids this inhibitory effect, making it a more focused and potent inhibitor.
Differences in Dosage and Clinical Effectiveness
The molecular distinction directly impacts dosing and clinical use. Because Escitalopram consists only of the active component, it is significantly more potent than Citalopram on a milligram-to-milligram basis. The standard therapeutic dose of Escitalopram is roughly half that of Citalopram; 10 mg of Escitalopram is considered therapeutically equivalent to 20 mg of Citalopram.
For treating major depressive disorder in adults, Citalopram typically starts at 20 mg per day, while Escitalopram starts at 10 mg per day. The maximum recommended dose for Escitalopram is 20 mg daily. Clinical trials suggest Escitalopram may demonstrate a slightly faster onset of action and potentially higher efficacy, especially in cases of severe depression.
FDA Indications
Both Citalopram and Escitalopram are approved for treating major depressive disorder in adults. Escitalopram holds additional FDA approval for treating Generalized Anxiety Disorder (GAD) in adults and pediatric patients aged seven and older.
Comparing Side Effect and Safety Profiles
The most important safety distinction relates to the risk of QTc interval prolongation, a dose-dependent delay in the heart’s electrical recovery period. This effect can increase the risk of Torsades de Pointes, a serious heart rhythm irregularity. The FDA issued a specific warning and dosage restriction for Citalopram, limiting the maximum daily dose to 40 mg for most adults and 20 mg for individuals over 60 or those with liver impairment.
Citalopram’s heightened cardiac risk is related to the combined effect of both the R- and S-enantiomers. Both enantiomers inhibit the hERG potassium channel in the heart, which causes QTc prolongation. Since Citalopram contains twice the total drug compound for an equivalent therapeutic dose, it delivers a greater overall cardiac load. Escitalopram, at its maximum recommended dose of 20 mg, causes less QTc prolongation, giving it a safer cardiac profile.
Both medications share similar common SSRI side effects, including nausea, dry mouth, headache, and dose-dependent sexual dysfunction. Citalopram, due to the R-enantiomer, exhibits a mild antagonist effect at the histamine H1 receptor that Escitalopram does not share. This difference can translate into a slightly higher chance of mild sedation with Citalopram, which may benefit patients experiencing insomnia. Escitalopram is often cited as having a better tolerability profile, leading to fewer patient discontinuations.