top of page
Psychopharmacology book

Citalopram (CELEXA)             

Citalopram (CELEXA)             

Citalopram (Celexa) is the old 50% pure version of escitalopram (Lexapro). 50% of Celexa is the right-handed enantiomer R-citalopram. S-citalopram is the most selective (for serotonin reuptake inhibition) of all SSRIs. R-citalopram is ineffective and causes QT interval prolongation. 

Celexa citalopram from Dr Jason Cafer MD's psychopharmacology book

The plasma concentration of S-citalopram (escitalopram) is usually one third of the total citalopram concentration, with the implication that the other two thirds of the total citalopram concentration is inactive as an antidepressant (Burke & Kratochvil, 2002). 

Escitalopram (Lexapro) compared to Citalopram (Lexapro) by Dr Jason Cafer MD

In 2012 the FDA released a warning for QT prolongation with Celexa and reduced the maximum approved dose from 60 mg to 40 mg. Lexapro does not have this warning. The warning may have been unwarranted, because rates of sudden unexpected death with high-dose citalopram is no higher than with other high-dose SSRIs (Ray et al, 2017). When VA patients were taken off citalopram because of the FDA warning, rates of depression increased and incidents of arrhythmias were not affected (Rector et al, 2016). 


Although rarely clinically significant, QT prolongation by R-citalopram poses some risk in overdose situations. Although the risk of single-drug overdose death with Celexa is only about 1 in 1,850, mortality risk is over 4x higher than with Lexapro. QT prolongation by Celexa could potentially be risky when it is prescribed along with other QT-prolonging medications.

Celexa citalopram from Dr Jason Cafer MD's psychopharmacology book - interactions and indications

Celexa 20 mg is roughly equivalent to Lexapro 10 mg, as would be expected, given that half of Celexa is junk. Even at double the milligram dose, Celexa is predictably less effective than Lexapro. L-citalopram has an allosteric effect at the serotonin transporter that R-citalopram interferes with. 


For initiation of antidepressant treatment, there is no reason to choose Celexa over Lexapro. So, why is anyone on citalopram? Many patients are on Celexa because, when their medication was started, Lexapro was more expensive. Celexa has been available generically since 2004. Lexapro went generic in 2012. When a drug goes off patent, it generally takes several years for enough manufacturers to enter the market for the drug to become dirt cheap. 


Of the other SSRIs, paroxetine (Paxil) and sertraline (Zoloft) have always been pure enantiomers. Fluvoxamine (Luvox) lacks a chiral center, so a mirror image molecule does not exist. Fluoxetine (Prozac) is a racemic mixture, but R-fluoxetine and L-fluoxetine inhibit serotonin reuptake equally. 


Bottom line: If starting an SSRI, choose escitalopram rather than citalopram. If a patient already established on citalopram is doing wonderfully, “don't try to fix what ain’t broken”. 


Dosing: Celexa is started at 20 mg QD, dosed in AM or PM. In about 4 weeks may increase to FDA maximum of 40 mg. If higher strength is needed, change to Lexapro 20 mg, which is predictable more effective than Celexa 40 mg.

Psychopharmacology book

Escitalopram (LEXAPRO)            

Escitalopram (LEXAPRO)            

Escitalopram (Lexapro) is the “pure” form of Celexa (citalopram). Escitalopram is the S-enantiomer of the molecule, as explained in the citalopram monograph. Compared to Celexa, Lexapro is safer, often better tolerated, and possibly more effective. There is no reason to choose citalopram over escitalopram—“S-citalopram is Superior to racemic citalopram”.


S for “Sinister” = L for Left-handed enantiomer

Lexapro escitalopram from Dr Jason Cafer MD's psychopharmacology book

Escitalopram is the best choice for a first-line antidepressant. It is the most selective inhibitor of the serotonin pump among all SSRIs. Several clinical trials and meta-analyses indicate escitalopram may be slightly more effective than other SSRIs. Escitalopram has an allosteric effect at the serotonin transporter that distinguishes it from other SSRIs. 10 mg of escitalopram is predictably more effective than 20 mg of citalopram (which contains 10 mg escitalopram and 10 mg R-citalopram). 

Lexapro escitalopram from Dr Jason Cafer MD's psychopharmacology book - interactions and indications

Lexapro has the fewest side effects of all the SSRIs. At the starting dose of 10 mg, side effects are comparable to placebo. It is unlikely to cause weight gain or sedation. It has minimal drug-drug interactions. Lexapro is safe. Risk of mortality with single-drug overdose on escitalopram is about 1 in 9,000 (Nelson & Spyker, 2017). 


For depression, escitalopram is at least as effective as SNRI antidepressants. Although venlafaxine (Effexor) and duloxetine (Cymbalta) have the additional mechanism of blocking the norepinephrine transporter, do not expect either of them to outperform Lexapro.


Although escitalopram may be the overall winner among SSRIs, with all psychotropic drugs there is marked inter-individual variability in tolerability and therapeutic response. If an individual is doing wonderfully on another antidepressant, there is usually no reason to change to escitalopram. 


Escitalopram is regarded as safe for pregnancy and breastfeeding, but sertraline (Zoloft) is safer.


Serum levels of escitalopram peak about 5 hours after ingestion. Half-life is around 30 hours, so steady-state concentration should be achieved within 7 days. Upon discontinuation, escitalopram should be cleared from the body within 7 days. 


Dosing: Start escitalopram 10 mg QD (AM or PM), after meals for the first few days, then with or without food.  May increase to 20 mg in one week, but generally you would wait about 4 weeks to see if it is necessary to advance the dose. Although the FDA max for Lexapro is 20 mg, it is not unusual to see it prescribed up to 30 mg for major depression. It can be safely dosed up to 60 mg daily for OCD (Stahl, 2016). When converting from citalopram (Celexa), use half the milligram dose of escitalopram. 20 mg of Lexapro is predictable more effective than 40 mg of Celexa.  Use a lower dose for elderly individuals because serum levels will be about 50% higher. If the patient is taking omeprazole (Prilosec) or esomeprazole (Nexium), consider starting escitalopram at 5 mg. Renal impairment: no adjustment needed. Hepatic impairment: consider lower dose. Taper to discontinue to avoid unpleasant serotonin withdrawal symptoms.  


Copyright 2021 CaferMed Publishing

bottom of page