Comparative efficacy of escitalopram in the treatment of major depressive disorder

Figures & data

Figure 1 Flow diagram for identification of pooled and meta-analysis studies of comparative efficacy of escitalopram.

Table 1 Pooled analysis studies of comparative efficacy of escitalopram in all patients

Author	Number of trials (patients, n)	Comparator	Primary outcome	Mean treatment difference	Response rates	Remission rates	Withdrawals (for adverse events)	Comments
Kennedy et al^Citation16	16 trials with all agents (n = 4549)	Citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine	MADRS	ESC > Comp, 1.1 points, P < 0.0001	ESC > Comp, 63.7% vs 58.3%, P < 0.0001	ESC > Comp, 53.1% vs 49.4%, P < 0.0059	ESC < Comp, 5.4% vs 7.9%, P < 0.0007	Also conducted subgroup analysis of four SNRI trials, but used the same data and had the same results as Kornstein et al 2009
	12 trials with SSRIs (n = 2964)	Citalopram, fluoxetine, paroxetine, sertraline	MADRS	ESC > SSRIs, 0.9 points, P = 0.0023	ESC > SSRIs, 62.1% vs 58.3%, P = 0.0089	ESC = SSRIs, 51.6% vs 49.0%, P = 0.0958	ESC = SSRIs, 5.4% vs 6.3%, P = ns	Pooled data from 12 of 15 identified randomized controlled trials with SSRIs
	5 trials with citalopram (n = 1583)	Citalopram	MADRS	ESC > CIT, 1.2 points, P = 0.0094	ESC > CIT, 59.7% vs 52.3%, P = 0.0043	ESC = CIT, 47.8% vs 42.7%, P = 0.0517	Not reported	Pooled data from 5 of 8 identified randomized controlled trials with citalopram
Kasper et al^Citation32	2 trials (n = 777)	Paroxetine	MADRS	ESC > PAR, 2.0 points, P < 0.01	ESC > PAR, 83% vs 76.8%, P < 0.05	ESC > PAR, 76.4% vs 70.0%, P < 0.05	ESC < PAR, 6.6% vs 11.7%, P < 0.01	Pooled data from 2 of 2 identified randomized controlled trials with paroxetine
Lam et al^Citation34	2 trials (n = 569)	Duloxetine	MADRS	ESC > DUL, 2.6 points, P < 0.01	ESC > DUL, 67.1% vs 53.2%, P < 0.001	ESC > DUL, 54.3% vs 44.4%, P < 0.05	ESC < DUL, 12.9% vs 24.3%, P < 0.001	Pooled data from 2 of 3 identified randomized controlled trials with duloxetine
Montgomery and Andersen^Citation33	2 trials (n = 483)	Venlafaxine XR	MADRS	ESC = VEN, 2.1 points, P = ns	ESC = VEN, 70% vs 67%, P = ns	ESC = VEN, 62% vs 58%, P = ns	ESC < VEN, 6.2% vs 13.3%, P < 0.01	Pooled data from 2 of 2 identified randomized controlled trials with venlafaxine XR
Kornstein et al^Citation35	4 trials (n = 1051)	Duloxetine, venlafaxine XR	MADRS	ESC > SNRIs 1.7 points, P < 0.01	ESC > SNRIs, 68.3% vs 59.0%, P < 0.01	ESC > SNRIs, 57.8% vs 50.5%, P < 0.05	ESC < SNRIs, 5.3% vs 12.0%, P < 0.0001	Pooled data from 4 of 5 identified randomized controlled trials with SNRIs
Clayton et al^Citation29	2 trials (n = 830)	Bupropion XL	Ham-D	ESC = BUP 0.4 points, P = ns	ESC = BUP, 65% vs 62%, P = ns	ESC = BUP, 45% vs 43%, P = ns	ESC = BUP, 4.3% vs 6.2%, P = ns	Pooled data from 2 of 2 identified randomized controlled trials with bupropion. ESC > BUP in worsened sexual functioning, 36% vs 20%, P < 0.001

Abbreviations: BUP, bupropion XL; ESC, escitalopram; CIT, citalopram; Comp, comparator; DUL, duloxetine; Ham-D, Hamilton Depression Rating Scale; MADRS, Montgomery Asberg Depression Rating Scale; ns, not significant; PAR, paroxetine; SNRI, serotonin noradrenaline reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; VEN, venlafaxine XR.

Table 2 Pooled analysis studies of comparative efficacy of escitalopram: subgroups of severely depressed patients

Author	Number of trials (patients, n)	Comparator	Primary outcome	Mean treatment difference	Response rates	Remission rates
Kennedy et al^Citation16	16 trials with all agents (n = 2345)	Citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine	MADRS	ESC > Comp, 1.8 points, P < 0.0001	ESC > Comp, 64.4% vs 55.8%, P < 0.0001	ESC > Comp, 47.7% vs 41.6%, P = 0.0017
	12 trials with SSRIs (n = 869)	Citalopram, fluoxetine, paroxetine, sertraline	MADRS	ESC > SSRIs, 1.4 points, P = 0.0004	ESC > SSRIs, 62.9% vs 56.3%, P = 0.0015	ESC = SSRIs, 45.8% vs 42.0%, P = 0.0811
	5 trials with citalopram (n = 742)	Citalopram	MADRS	ESC > CIT, 2.0 points, P = 0.0013	ESC > CIT, 61.2% vs 49.9%, P = 0.0012	ESC = CIT, 41.8% vs 35.5%, P = 0.0640
Kasper et al^Citation32	2 trials (n = 606)	Paroxetine	MADRS	ESC > PAR, 2.6 points, P < 0.01	ESC > PAR 82.6% vs 75.7%, P < 0.05	ESC > PAR 69.0% vs 60.1%, P < 0.05
Lam et al^Citation34	2 trials (n = 371)	Duloxetine	MADRS	ESC > DUL, 3.7 points, P < 0.01	ESC > DUL, 68.8% vs 49.7%, P < 0.001	ESC > DUL, 51.7% vs 37.4%, P < 0.01
Montgomery and Andersen^Citation33	2 trials (n = 121)	Venlafaxine XR	MADRS	ESC > VEN, 3.8 points, P < 0.05	Not reported	Not reported
Kornstein et al^Citation35	4 trials (n = 622)	Duloxetine, venlafaxine XR	MADRS	ESC > SNRIs 2.9 points, P < 0.001	ESC > SNRIs 68.7% vs 54.3%, P < 0.001	ESC > SNRIs 53.0% vs 40.4%, P < 0.001

Abbreviations: Comp, comparator; ESC, escitalopram; CIT, citalopram; DUL, duloxetine; MADRS, Montgomery Asberg Depression Rating Scale; PAR, paroxetine; SNRI, serotonin noradrenaline reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; VEN, venlafaxine XR.

Table 3 Meta-analysis studies of comparative efficacy of escitalopram

Author	Number of trials (patients, n)	Comparator	Mean difference	Response rates	Remission rates	Withdrawals (for adverse events)	Comments
Gartlehner et al^Citation37	114 trials with all agents (n = 26,349)	Bupropion, duloxetine, fluoxetine, fluvoxamine mirtazapine, nefazodone paroxetine, sertraline, trazodone, venlafaxine	Not reported	No differences in any comparisons	Not reported	No individual comparisons reported	Used indirect comparisons (including placebo-controlled randomized controlled trials) with modified network meta-analysis and meta-regression techniques.
	5 trials (n = 1359)	Citalopram	ESC > CIT, WMD = 1.13 MADRS points (CI 0.18–2.09)	ESC > CIT, RR = 1.14 (CI 1.04–1.26)	Not reported	Not reported	Direct meta-analysis
Cipriani et al^Citation36	14 trials with all agents (n = 5921)	Bupropion, duloxetine, paroxetine, sertraline, venlafaxine	No differences in any comparisons	No differences in any comparisons	No differences in any comparisons	No differences in any comparisons	Cochrane systematic review – includes comprehensive search of all available randomized controlled trials to July 2008
	3 trials (n = 783)	Fluoxetine	ESC > FLU, SMD = 0.17, P < 0.02	ESC = FLU, OR = 0.81, P = ns	ESC = FLU OR = 0.86, P = ns	No differences
	6 trials (n = 1823)	Citalopram	ESC > CIT, SMD = 0.17, P = 0.009	ESC > CIT, OR = 0.67 (CI 0.50–0.87)	ESC > CIT OR = 0.53 (CI 0.30–0.93)	No differences
Trkulja^Citation38	7 trials (n = 2476)	Citalopram	ESC > CIT, WMD = 1.232 points (CI 0.27–2.195) SMD = 0.131 (CI 0.027–0.322)	ESC > CIT, RR = 1.144 (CI 1.037–1.262)	Not reported	ESC = CIT 4.4% vs 4.7%, P = ns	Analyzed based on week to week outcomes. Figures in this table based on 8-week outcomes (5 trials)
Montgomery et al^Citation39	9 trials (n = 2009)	Citalopram	ESC > CIT, WMD = 1.7 MADRS points, P = 0.0002	ESC > CIT, OR = 1.44, P = 0.0003	ESC > CIT, OR = 1.86 P < 0.0001	Not reported	Included one nonrandomized trial^Citation55
Kennedy et al^Citation16	3 trials (n = 1111)	Duloxetine	ESC = DUL, WMD = 0.22 Ham-D points, P = ns	Not reported	Not reported	Not reported	Used results from mixed model repeated measures analyses of Ham-D data from primary randomized controlled trials
	5 trials (n = 1598)	Duloxetine, venlafaxine	ESC = SNRIs, WMD = 0.18 Ham-D points, P = ns	Not reported	Not reported	Not reported	Used results from mixed model repeated measures analyses of Ham-D data from primary randomized controlled trials
Cipriani et al^Citation42	117 trials with all agents (n = 25,928)	Bupropion, citalopram, duloxetine, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine	Not reported	ESC > CIT OR = 1.47 (CI 1.15–1.90) Superior response for escitalopram, mirtazapine, sertraline, and venlafaxine	Not reported	Superior acceptability (all-cause withdrawals) for bupropion, citalopram, escitalopram, and sertraline	Multiple treatments (network) meta-analysis using direct and indirect comparisons

Abbreviations: ESC, escitalopram; CI, 95% confidence interval; CIT, citalopram; DUL, duloxetine; FLU, fluoxetine; Ham-D, Hamilton Depression Rating Scale; MADRS, Montgomery Asberg Depression Rating Scale; ns, not significant; OR, odds ratio; PAR, paroxetine; SMD, standardized mean difference; RR, relative risk; SNRI, serotonin noradrenaline reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; WMD, weighted mean difference.

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