Efficacy comparison of duloxetine and SSRIs at doses approved in Japan

Figures & data

Table 1 Studies included in pooled analysis

Studies	Inclusion criteria	Duration (weeks)	Treatment	n
HMAT A	MDD HAMD ≥15 CGI-S ≥4	8	DLX 40 mg, 80 mga paroxetine 20 mg	DLX 91b SSRI 89
HMAT B	MDD HAMD ≥15 CGI-S ≥4	8	DLX 40 mg, 80 mga paroxetine 20 mg	DLX 86b SSRI 87
HMCR	MDD MADRS ≥22 CGI-S ≥4	8	DLX 60 mg escitalopram 10 mg	DLX 273 SSRI 274
HMCV	MDD HAMD ≥15 CGI-S ≥4	9	DLX 60 mg paroxetine 20 mg	DLX 238 SSRI 240

Notes:

a 80 mg dose were excluded from the analysis

b DLX 40 mg arm.

Abbreviations: CGI-S, Clinical Global Impression-Severity; DLX, duloxetine; HAMD, Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale; MDD, major depressive disorder; n, number of patients; SSRI, selective serotonin reuptake inhibitor.

Table 2 Patient demographics

Characteristics	Total (n=1,694)	Duloxetine (n=688)	SSRI (n=690)	Placebo (n=316)
Age
Mean (SD)	41.3 (13.4)	40.8 (12.9)	41.4 (14.0)	42.0 (13.1)
Gender, n (%)
Female	1,107 (65.3)	439 (63.8)	465 (67.4)	203 (64.2)
Male	587 (34.7)	249 (36.2)	225 (32.6)	113 (35.8)
Race/ethnicity, n (%)
Caucasian	988 (58.3)	370 (53.8)	360 (52.2)	258 (81.6)
East Asian	459 (27.1)	226 (32.8)	231 (33.5)	2 (0.6)
African descent	130 (7.7)	50 (7.3)	46 (6.7)	34 (10.8)
Other	117 (6.9)	42 (6.1)	53 (7.7)	22 (7.0)
Geographical region, n (%)
USA	1,216 (71.8)	450 (65.4)	450 (65.2)	316 (100)
China	244 (14.4)	121 (17.6)	123 (17.8)	0 (0.0)
Korea	123 (7.3)	61 (8.9)	62 (9.0)	0 (0.0)
Taiwan	68 (4.0)	34 (4.9)	34 (4.9)	0 (0.0)
Brazil	43 (2.5)	22 (3.2)	21 (3.0)	0 (0.0)
Number of previous episodes
Mean (SD)	4.2 (21.2)	4.7 (30.2)	3.5 (12.2)	4.8 (9.3)
Duration of current episode (months)
Mean (SD)	13.0 (27.8)	12.6 (21.7)	12.7 (32.6)	14.6 (28.4)
MADRS total score at baseline
Mean (SD)	26.9 (7.2)	27.2 (7.1)	27.3 (7.1)	26.0 (7.5)
HAMA total score at baseline
Mean (SD)	15.5 (5.9)	15.7 (5.9)	15.8 (6.0)	14.4 (5.3)
HAMD total score at baseline
Mean (SD)	18.7 (5.1)	18.9 (5.1)	19.0 (5.1)	17.6 (5.0)

Abbreviations: HAMA, Hamilton Rating Scale for Anxiety; HAMD, Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale; N, total number of patients; n, total number of affected patients; SD, standard deviation; SSRI, selective serotonin reuptake inhibitor.

Table 3 Reasons for discontinuation

Parameter	Duloxetine (N=688)	SSRI (N=690)	Placebo (N=316)
Patients completed, n (%)	472 (68.6)	499 (72.3)	211 (66.8)
Patients discontinued, n (%)	216 (31.4)	190 (27.5)	105 (33.2)
Adverse events	61 (8.9)	49 (7.1)	19 (6.0)
Death	0	1 (0.1)	0
Lack of efficacy	22 (3.2)	22 (3.2)	42 (13.3)
Lost to follow-up	38 (5.5)	30 (4.3)	18 (5.7)
Physician decision	1 (0.1)	5 (0.7)	2 (0.6)
Protocol violation	19 (2.8)	21 (3.0)	7 (2.2)
Sponsor decision	1 (0.1)	1 (0.1)	0
Subject decision	74 (10.8)	61 (8.8)	17 (5.4)
Unknown	0	1 (0.1)	0

Abbreviations: N, total number of patients; n, number of affected patients; SSRI, selective serotonin reuptake inhibitor.

Figure 1 Effect sizes for duloxetine and SSRIs versus placebo in mean changes on HAMD₁₇ total score, HAMD₁₇ subscale score, and HAMA total score at week 8. Total population (HAMD₁₇ ≥15) and more severe population (HAMD₁₇ ≥19).

Abbreviations: HAMA, Hamilton Anxiety Rating Scale; HAMD₁₇, 17-item Hamilton Rating Scale for Depression; SSRIs, selective serotonin reuptake inhibitor.

Table 4 Changes in HAMD₁₇ total and subscale scores

Items	LS mean change (95% CI)	LS mean change (95% CI)	LS mean change (95% CI)	LS mean difference* (95% CI)	P-value	LS mean difference* (95% CI)	P-value	LS mean difference* (95% CI)	P-value
Total population HAMD total score ≥15	Duloxetine n=688	SSRI n=690	Placebo n=316	Duloxetine versus SSRI		Duloxetine versus placebo		SSRI versus placebo
HAMD17 total score	−10.08 (−10.63, −9.53)	−9.69 (−10.22, −9.16)	−6.03 (−6.86, −5.21)	−0.47 (−1.15, 0.20)	0.168	−1.47 (−2.49, −0.46)	0.004	−1.40 (−2.41, −0.40)	0.006
HAMD17 subscale score
Bech	−5.86 (−6.17, −5.54)	−5.56 (−5.86, −5.25)	−3.59 (−4.10, −3.07)	−0.33 (−0.72, 0.06)	0.093	−1.24 (−1.87, −0.61)	<0.001	−1.13 (−1.76, −0.51)	<0.001
Maier	−5.68 (−5.98, −5.37)	−5.41 (−5.71, −5.11)	−3.37 (−3.85, −2.89)	−0.31 (−0.68, 0.07)	0.112	−1.22 (−1.81, −0.64)	<0.001	−1.11 (−1.69, −0.52)	<0.001
Retardation	−3.82 (−4.04, −3.60)	−3.50 (−3.72, −3.29)	−2.36 (−2.70, −2.02)	−0.33 (−0.60, −0.07)	0.015	−0.79 (−1.21, −0.37)	<0.001	−0.43 (−0.85, −0.01)	0.045
Sleep	−1.57 (−1.71, −1.43)	−1.61 (−1.75, −1.48)	−1.05 (−1.28, −0.83)	0.02 (−0.15, 0.20)	0.797	0.03 (−0.24, 0.31)	0.821	−0.11 (−0.30, 0.16)	0.425
Anxiety	−2.83 (−3.04, −2.61)	−2.70 (−2.91, −2.50)	−1.71 (−2.02, −1.40)	−0.14 (−0.40, 0.12)	0.281	−0.32 (−0.70, 0.06)	0.103	−0.39 (−0.77, −0.01)	0.045
HAMA	−7.25 (−7.76, −6.73)	−6.95 (−7.44, −6.45)	−4.69 (−5.42, −3.96)	−0.36 (−1.00, 0.27)	0.260	−0.74 (−1.64, 0.15)	0.103	−0.79 (−1.67, 0.10)	0.084
Subgroup HAMD total score ≥19	Duloxetine n=377	SSRI n=383	Placebo n=141	Duloxetine versus SSRI		Duloxetine versus placebo		SSRI versus placebo
HAMD17 total score	−12.57 (−13.41, −11.73)	−11.83 (−12.64, −11.02)	−7.81 (−9.31, −6.30)	−0.79 (−1.78, 0.20)	0.117	−2.17 (−4.00, −0.34)	0.020	−2.14 (−3.98, −0.30)	0.023
HAMD17 subscale score
Bech	−6.81 (−7.28, −6.14)	−6.17 (−6.62, −5.71)	−4.46 (−5.35, −3.57)	−0.62 (−1.16, −0.08)	0.025	−1.51 (−2.59, −0.44)	0.006	−1.04 (−2.14, 0.05)	0.062
Maier	−6.79 (−7.25, −6.34)	−6.13 (−6.57, −5.69)	−4.16 (−5.01, −3.30)	−0.65 (−1.18, −0.12)	0.017	−1.64 (−2.67, −0.61)	0.002	−1.16 (−2.20, −0.11)	0.031
Retardation	−4.43 (−4.76, −4.11)	−3.94 (−4.26, −3.62)	−2.78 (−3.37, −0.28)	−0.45 (−0.83, −0.07)	0.020	−0.99 (−1.71, −0.28)	0.007	−0.38 (−1.11, 0.35)	0.307
Sleep	−2.16 (−2.37, −1.94)	−2.18 (−2.38, −1.97)	−1.48 (−1.90, −1.06)	−0.03 (−0.28, 0.22)	0.825	−0.21 (−0.71, 0.30)	0.424	−0.42 (−0.93, 0.08)	0.102
Anxiety	−3.47 (−3.78, −3.15)	−3.23 (−3.53, −2.92)	−2.31 (−2.87, −1.76)	−0.25 (−0.62, 0.12)	0.188	−0.40 (−1.06, 0.27)	0.242	−0.45 (−1.12, 0.21)	0.184
HAMA	−9.21 (−9.98, −8.44)	−8.60 (−9.34, −7.86)	−5.86 (−7.14, −4.57)	−0.59 (−1.51, 0.33)	0.207	−1.31 (−2.85, 0.23)	0.955	−1.30 (−2.86, 0.25)	0.101

Note:

* LS mean difference: a minus value indicates better reduction than comparator.

Abbreviations: CI, confidence interval; HAMA, Hamilton Anxiety Scale; HAMD, Hamilton Rating Scale for Depression; LS, least squares; n, total number of patients; SSRI, selective serotonin reuptake inhibitor.

Table 5 Adverse events with >5% incidence

Parameter	Duloxetine (n=688)	SSRI (n=690)	Placebo (n=316)
Patients with at least one TEAE	569 (82.7)	533 (77.2)	234 (74.1)
Nausea	177 (25.7)	115 (16.7)	19 (6.0)
Headache	113 (16.4)	117 (17.0)	52 (16.5)
Dry mouth	119 (17.3)	77 (11.2)	21 (6.6)
Dizziness	87 (12.6)	81 (11.7)	18 (5.7)
Constipation	76 (11.0)	62 (9.0)	17 (5.4)
Decreased appetite	82 (11.9)	55 (8.0)	7 (2.2)
Diarrhea	46 (6.7)	66 (9.6)	26 (8.2)
Somnolence	57 (8.3)	56 (8.1)	10 (3.2)
Insomnia	54 (7.8)	39 (5.7)	17 (5.4)
Fatigue	38 (5.5)	42 (6.1)	17 (5.4)

Abbreviations: n, total number of patients; SSRI, selective serotonin reuptake inhibitors; TEAE, treatment-emergent adverse event.