Citalopram (Celexa®) versus Fluoxetine (Prozac®)

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

Citalopram advantages over Fluoxetine

Low potential for drug interactions. Unlike fluoxetine, citalopram is a weak inhibitor of all CYP isoenzymes.
Citalopram is a better option for patients with anxiety or sleep problems.

Fluoxetine advantages over Citalopram

Good safety in patients with cardiovascular problems. Fluoxetine does not affect QTc interval and is not associated with arrhythmias.
Effective for patients with hypochondria (illness anxiety disorder) and somatization disorder.
Fluoxetine is more energizing than citalopram. So it is a better antidepressant for patients with excessive sleepiness, apathy, or fatigue.
Missing a dose may not be a problem. Good option for patients with poor medication compliance.
Fluoxetine is licensed for treatment of major depressive disorder in children and adolescents 8 years and older.

Difference between Citalopram and Fluoxetine

Table 1. Comparison of Citalopram and Fluoxetine

Citalopram	Fluoxetine
Brand names
Celexa®	Prozac® Serafem®
Drug class
Selective serotonin reuptake inhibitor (SSRI), Antidepressant
Dose formulations
• Tablets • Solution, oral	• Capsules • Tablets • Capsules, delayed-release • Solution, oral
Legal status
• Rx only • Not a controlled drug
FDA-approved indications
• Depression
	• Premenstrual dysphoric disorder (severe form of premenstrual syndrome) • Obsessive-compulsive disorder • Bulimia nervosa • Panic disorder
"Off-label" uses
• Premature ejaculation 1 • Facilitation of motor recovery after ischemic stroke9
• Generalized anxiety disorder	• Social anxiety • Chronic fatigue • Cataplexy2 • Anorexia nervosa • Neurocardiogenic syncope
Mechanism of action
• Selectively inhibits reabsorption (reuptake) of serotonin in the brain.
Half-life
• 36 hours	• 4-6 days (long-term use) • 1-3 days (after a single dose)
Oral bioavailability
• 80%	• 60–80%
Metabolism, Elimination
• Citalopram is metabolized by isoenzymes CYP2C19, CYP3A4, and CYP2D6. • Citalopram is excreted via liver (85%) and kidneys (15%).	• Fluoxetine is metabolized in the liver by hepatic enzyme CYP2D6 to its active metabolite norfluoxetine. • Eliminated in urine (18%), small amounts in feces.
Contraindications
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping an MAOI.
• Hypersensitivity to citalopram • Concomitant use with pimozide - increased risk of QT interval prolongation • History QT interval prolongation (in several countries, not in U.S.)	• Hypersensitivity to fluoxetine
Side effects
• Increased sweating • Nausea • Tremor • Drowsiness • Diarrhea • Dry mouth • Impaired ejaculation • Impotence • Headache	• Headache • Nausea • Insomnia • Nervousness • Anorexia • Anxiety • Weakness • Diarrhea • Somnolence • Tremor • Impaired ejaculation • Impotence
• Citalopram delays ejaculation more significantly than fluoxetine8.
Drug interactions
• Monoamine oxidase inhibitors - concomitant use contraindicated • Serotonergic medications
• Pimozide - concomitant use increases the QTc interval	• Drugs metabolized by CYP2D6 - fluoxetine is a potent CYP2D6 inhibitor

Citalopram vs Fluoxetine for Depression

Fluoxetine and citalopram are similarly effective in the treatment of major depression. Citalopram may provide earlier improvement of symptoms than fluoxetine 4.

Both antidepressants improve sleep quality in patients with depression3.

Citalopram vs Fluoxetine for Obsessive-compulsive disorder

Fluoxetine and citalopram have equivalent efficacy and safety in the treatment of Obsessive-compulsive disorder5. Most common side effects are headache with citalopram and tremor with fluoxetine.

Citalopram vs Fluoxetine for Bulimia nervosa

Fluoxetine is more effective for introjected anger in patients with bulimia nervosa than citalopram6. On the other hand, citalopram works better in improving depression feelings in bulimic patients than does fluoxetine.

Citalopram vs Fluoxetine for Postmenopausal symptoms

Both citalopram and fluoxetine don't provide sufficient therapeutic benefits for hot flushes7. Citalopram may be helpful for insomnia in postmenopausal women.

References

1. Dadfar MR, Baghinia MR. Salvage use of citalopram for treatment of fluoxetine-resistant premature ejaculation in recently married men. Urol J. 2010 Winter;7(1):40-4.
2. Morgenthaler TI, Kapur VK, Brown T, Swick TJ, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007 Dec;30(12):1705-11. PubMed
3. Shahsavand-Ananloo E, Berenji F, Sadeghniiat K, et al. Comparing effects of citalopram with fluoxetine on sleep quality in patients with major depressive disorder. Eur Rev Med Pharmacol Sci. 2013 May;17(9):1155-61.
4. Patris M, Bouchard JM, Bougerol T, et al. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.IntClinPsychopharmacol. 1996 Jun;11(2):129-36. PubMed
5. Alaghband-Rad J, Hakimshooshtary M.A randomized controlled clinical trial of citalopram versus fluoxetine in children and adolescents with obsessive-compulsive disorder. Eur Child Adolesc Psychiatry. 2009 Mar;18(3):131-5.
6. Leombruni P, Amianto F, Delsedime N, Gramaglia C, Abbate-Daga G, Fassino S. Citalopram versus fluoxetine in bulimia nervosa: a single-blind randomized controlled trial. Adv Ther. 2006 May-Jun;23(3):481-94. PubMed
7. Suvanto-Luukkonen E, Koivunen R, Sundström H, Bloigu R, Karjalainen E, Häivä-Mällinen L, Tapanainen JS.Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 2005 Jan-Feb;12(1):18-26.
8. Madeo B, Bettica P, Milleri S, Balestrieri A, Granata AR, Carani C, Rochira V. The effects of citalopram and fluoxetine on sexual behavior in healthy men. J Sex Med. 2008 Oct;5(10):2431-41 PubMed
9. Asadollahi M, Ramezani M, Khanmoradi Z, Karimialavijeh E. The efficacy comparison of citalopram, fluoxetine, and placebo on motor recovery after ischemic stroke: a double-blind placebo-controlled randomized controlled trial. Clin Rehabil. 2018 Aug;32(8):1069-1075.

Published: November 20, 2017
Last updated: August 12, 2018