Escitalopram for the management of major depressive disorder: a review of its efficacy, safety, and patient acceptability

Abstract

Escitalopram (escitalopram oxalate; Cipralex(®), Lexapro(®)) is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD) and anxiety disorder. This drug exerts a highly selective, potent, and dose-dependent inhibitory effect on the human serotonin transport. By inhibiting the reuptake of serotonin into presynaptic nerve endings, this drug enhances the activity of serotonin in the central nervous system. Escitalopram also has allosteric activity. Moreover, the possibility of interacting with other drugs is considered low. This review covers randomized, controlled studies that enrolled adult patients with MDD to evaluate the efficacy of escitalopram based on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. The results showed that escitalopram was superior to placebo, and nearly equal or superior to other SSRIs (eg, citalopram, paroxetine, fluoxetine, sertraline) and serotonin-noradrenaline reuptake inhibitors (eg, duloxetine, sustained-release venlafaxine). In addition, with long-term administration, escitalopram has shown a preventive effect on MDD relapse and recurrence. Escitalopram also showed favorable tolerability, and associated adverse events were generally mild and temporary. Discontinuation symptoms were milder with escitalopram than with paroxetine. In view of the patient acceptability of escitalopram, based on both a meta-analysis and a pooled analysis, this drug was more favorable than other new antidepressants. The findings indicate that escitalopram achieved high continuity in antidepressant drug therapy.

Keywords: MDD; SSRI; allosteric action; discontinuation symptoms; escitalopram.

Figure 1

Chemical structure of escitalopram.

Figure 2

Escitalopram showed 5-HT transporter occupancy that outlived its plasma concentration. Notes: Escitalopram (10 mg) was administered once daily for 10 consecutive days (the first 5 days are shown) to six healthy men. The 5-HT transporter occupancy rate was determined in the midbrain-hypothalamus region. The 5-HT transporter occupancy rate of escitalopram peaked at 80% and the occupancy half-life was 130 hours. Copyright © 2007, Springer-Verlag. Adapted with permission from Klein N, Sacher J, Geiss-Granadia T, et al. Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study. Psychopharmacology (Berl). 2007;191(2):333–339.

Figure 3

Changes in the cumulative non-relapse rate. Notes: Escitalopram exhibits a low relapse rate, demonstrating a significant relapse-preventing effect compared to placebo. Copyright © 2007, Wolters Kluwer Health. Adapted with permission from Gorwood P, Weiller E, Lemming O, Katona C. Escitalopram prevents relapse in older patients with major depressive disorder. Am J Geriatr Psychiatry. 2007;15(7):581–593.

Figure 4

Discontinuation Emergent Signs and Symptoms (DESS 47) scores in the post-therapy observation period. Notes: The change in the total modified DESS 47 score was calculated from the beginning of post-therapy observation to the end of one week with either alternate-day dosing or placebo. The mean scores are indicated in the bars. Scores were −0.02 for the escitalopram group and 1.28 for the paroxetine group. The corresponding values at 1 week of placebo administration were 1.63 for the escitalopram group and 3.42 for the paroxetine group. Significantly fewer post-therapy symptoms were observed in the escitalopram group than in the paroxetine group at all times. Copyright © 2006, Lippincott Williams & Wilkins. Adapted with permission from Baldwin DS, Cooper JA, Huusom AK, Hindmarch I. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder. Int Clin Psychopharmacol. 2006;21(3):159–169.

Figure 5

Efficacy and patient acceptability of new antidepressant drugs. Notes: The odds ratios (OR) of acceptability and efficacy were based on a value of 1 for fluoxetine. Acceptability of escitalopram was highest among the new antidepressant drugs examined. Copyright © 2009, The Family Physician’s Inquiries Network (FPIN). Adapted with permission from Patrick G, Combs G, Gavagan T. Initiating antidepressant therapy? Try these 2 drugs first. J Fam Pract. 2009;58(7):365–369. Abbreviation: OR, odds ratio.