title: A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?
abstract: 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.
authors.affiliation: 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.
authors.forename: Connie
authors.initials: C
authors.lastname: Sanchez
authors.forename: Elin H
authors.initials: EH
authors.lastname: Reines
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Montgomery
mesh_terms: D000495:Allosteric Site; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D004347:Drug Interactions; D019317:Evidence-Based Medicine; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017374:Paroxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline