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A comparative review of escitalopram, paroxetine, and sertraline: are they all alike?

Sanchez, Conniea; Reines, Elin H.b; Montgomery, Stuart A.c

International Clinical Psychopharmacology: July 2014 - Volume 29 - Issue 4 - p 185–196
doi: 10.1097/YIC.0000000000000023

It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.

aExternal Sourcing, Lundbeck Research USA Inc., Paramus, New Jersey, USA

bInternational Clinical Research, H. Lundbeck A/S, Copenhagen, Denmark

cImperial College School of Medicine, University of London, London, UK

Correspondence to Connie Sanchez, External Sourcing, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA Tel: +1 201 350 0103; fax: +1 201 261 0623; e-mail:

Received May 1, 2013

Accepted October 25, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins