Escitalopram (Lexapro) versus Citalopram (Celexa)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Escitalopram advantages over Citalopram:

• Escitalopram generally causes side effects less frequently than does citalopram, particularly sedation and fatigue.
• Escitalopram may be more effective for severe depression.
• Escitalopram is not associated with risk of ventricular arrhythmia1.

Citalopram advantages over Escitalopram:

• The only principal advantage of citalopram is its cost. It is less expensive than escitalopram.
• Effectiveness of both antidepressants is generally equal except for rare certain situations.

Table 1. Difference between Escitalopram and Citalopram chart

	Escitalopram Lexapro®	Citalopram Celexa®
Drug class	Antidepressant, Selective Serotonin Reuptake Inhibitor
Stereochemistry	S-enantiomer of racemic citalopram. S-enantiomer is considered the active component of the racemate.	Racemic mixture of R- and S-enantiomers.
Common FDA approved indications	• Major depressive disorder in adults and adolescents 12-17 years of age	•   Major depressive disorder • Citalopram is not approved for patients younger than 18 years
Other FDA-approved indications	• Generalized anxiety disorder	• Citalopram is prescribed for anxiety disorders "off-label".
Mechanism of action	SSRIs enhance serotonergic activity in the central nervous system via blockade of serotonin (5-HT) reuptake.
	• Escitalopram also works as allosteric modulator of the serotonin transporter14.	• Citalopram has mild affinity for H1 histamine receptors.
Starting dose	10 mg	20 mg
Maximum dose	20 mg	40 mg
Half-life	27-32 hours	36 hours
Oral bioavailability	80%	80%
Metabolism	• Escitalopram is metabolized to S-demethylcitalopram and S-didemethylcitalopram by the cytochrome P450 isoenzymes CYP2C19, CYP2D6 and CYP3A4.	• Citalopram is metabolized by the cytochrome P450 isoenzymes CYP2C19, CYP2D6 and CYP3A4 to its major metabolite, demethylcitalopram, and other metabolites.
Contraindications/ warnings	• Concomitant use with MAOIs • Concomitant use with Pimozide • Hypersensitivity to escitalopram or citalopram
Side effects	Most common undesirable effects are nausea, diarrhea, insomnia, somnolence, ejaculation disorder, impotence, fatigue, dry mouth, and dizziness.
		• Citalopram has mild antihistamine properties and may produce more sedation, fatigue, and sleepiness. • Citalopram has been associated with a small increase in the risk of ventricular arrhythmia in older patients 1.
Safety in overdose	• Escitalopram is less dangerous than citalopram after an acute overdose 4. Escitalopram causes fewer seizures and tremors in overdose than citalopram 3
Withdrawal symptoms	The incidence of adverse events and withdrawals does not differ significantly between escitalopram and citalopram 2
Drug interactions	Low risk
Cost	In most countries escitalopram is more expensive than citalopram

Escitalopram vs Citalopram for depression

In several clinical studies escitalopram was significantly more effective than citalopram, including higher rates of response and remission6, 9. Escitalopram is more effective than citalopram in the treatment of severe depression 8.

The inferior efficacy of citalopram in the studies is attributed to the inhibition of the effect of the S-enantiomer by the R-enantiomer7, 12.

However, there is evidence that in the short-to-medium term treatment of major depressive disorder escitalopram and citalopram are equally effective10, 13.

Geriatric patients
Escitalopram may offer better treatment compliance, fewer hospitalizations, and lower total cost of healthcare in the treatment of major depression in geriatric patients 5.

Antinociceptive properties
Animal research shows that citalopram injected intraperitoneally is a weak antinociceptor, while escitalopram has no antinociceptive properties 11.

Results of prospective, randomized, double-blind, active-controlled study of escitalopram versus citalopram in major depressive disorder 6.	Escitalopram	Citalopram
Regimen	10 mg daily for 6 weeks	20 mg daily for 6 weeks
Mean change from baseline in MADRS total score at the end of study	-28.70	-25.19
Mean change from baseline in MADRS total score in the severely depressed subgroup	-30.33	-26.34
Changes in the Clinical Global Impression-Severity and Improvement scores	-2.60 +1.58	-2.05 +1.80
Response rate	95.4%	83.3%
Remission rate	89.8%	50.9%
Adverse effects, most frequently reported:
nausea	1.9%	6.5%
headache	0.9%	3.7%

Results of randomized, double-blind study of escitalopram versus citalopram in major depressive disorder 9.	Escitalopram	Citalopram
Regimen	20 mg daily over 8 weeks	40 mg daily over 8 weeks
Premature withdrawal, number of patients	6 of 138 patients	15 of 142 patients
Change in the MADRS total score from baseline to last assessment	-22.4+/-12.9	-20.3+/-12.7
Response rate	76.1%	61.3%
Remission rate	56.1%	43.6%
Tolerability	similar

Further reading

• Escitalopram (Lexapro) Facts
• Citalopram vs Fluoxetine
• Escitalopram vs Duloxetine

References

• 1. Qirjazi E, McArthur E, Nash DM, et al. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study. PLoS One. 2016 Aug 11;11(8):e0160768. PubMed
• 2. Ou JJ, Xun GL, Wu RR, et al. Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study. Psychopharmacology (Berl). 2011 Feb;213(2-3):639-46. PubMed
• 3. Yilmaz Z, Ceschi A, Rauber-Lüthy C, et al. Escitalopram causes fewer seizures in human overdose than citalopram. Clin Toxicol (Phila). 2010 Mar;48(3):207-12. PubMed
• 4. Hayes BD, Klein-Schwartz W, Clark RF, Muller AA, Miloradovich JE. Comparison of toxicity of acute overdoses with citalopram and escitalopram. J Emerg Med. 2010 Jul;39(1):44-8. PubMed
• 5. Wu E, Greenberg PE, Yang E, Yu A, Erder MH. Comparison of escitalopram versus citalopram for the treatment of major depressive disorder in a geriatric population. Curr Med Res Opin. 2008 Sep;24(9):2587-95 PubMed
• 6. Yevtushenko VY, Belous AI, Yevtushenko YG, Gusinin SE, Buzik OJ, Agibalova TV. Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients. Clin Ther. 2007 Nov;29(11):2319-32. PubMed
• 7. Jacquot C, David DJ, Gardier AM, Sánchez C. Escitalopram and citalopram: the unexpected role of the R-enantiomer. Encephale. 2007 Mar-Apr;33(2):179-87. PubMed
• 8. Azorin JM, Llorca PM, Despiegel N, Verpillat P. Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder. Encephale. 2004 Mar-Apr;30(2):158-66. PubMed
• 9. Moore N, Verdoux H, Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005 May;20(3):131-7. PubMed
• 10. Trkulja V. Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials. Croat Med J. 2010 Feb;51(1):61-73. PubMed
• 11. Schreiber S, Pick CG. From selective to highly selective SSRIs: a comparison of the antinociceptive properties. Eur Neuropsychopharmacol. 2006 Aug;16(6):464-8. PubMed
• 12. Sanchez C, Bogeso KP, Ebert B, et al. Escitalopram versus citalopram: the surprising role of the R-enantiomer. Psychopharmacology (Berl). 2004 Jul;174(2):163-76.
• 13. Li H, Li T, Li G, Luo J. Citalopram and escitalopram in the treatment of major depressive disorder. Ann Clin Psychiatry. 2014 Nov;26(4):281-7.
• 14. Zhong H, Haddjeri N, Sanchez C. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter. Psychopharmacology (Berl). 2012 Jan;219(1):1-13.

Published: January 02, 2017
Last updated: December 23, 2017