Electronic supplementary material

Study
/ Na / Study duration (weeks)/ Setting / Age
[years]b / Gender
f [%] / HAM-D17 baselineb
/ MADRS baseline / Venlafaxin-group / Venlafaxin Mean Dosagee / Drop out
N (%)
Allard 2004
Venlafaxine 75-150mg
Citalopram 10-20mg / 76/73
75/75 / 24
Outpatients / 74 (6)
73 (6) / 79
80 / - / 27,6 (3,6)
28,0 (3,6) / Experimental / n.m / n.m.
Alves 1999
Venlafaxine 75-150mg
Fluoxetine 20-40mg / 40/n.m.
47/n.m. / 12
Outpatients / 45 (12)
42 (12) / 93
92 / 27,9 (5,2)
26,9 (3,9) / 31,2 (6,8)
29,8 (5,8) / Experimental / n.m. / 10 (25)
9 (19)
Bielski 2004
Venlafaxine XR 225 mg
Escitalopram 20 mg / n.m./98
n.m./97 / 8
Outpatients / 38 (12)
37 (12) / 47
70 / 27,4 (4,5)
28,6 (4,1) / 30,0 (5,0)
30,7 (4,6) / Comparator / fixed / 34 (34)
26 (27)
Clerc 1994
Venlafaxine 200mg
Fluoxetine 40 mg / 34/33
34/34 / 6
Inpatients / 49 (n.m.)
54 (n.m.) / 68
68 / 29,1 (5,2)
29,7 (4,2) / 34,8 (5,0)
35,7 (5,0) / Experimental / fixed / 6 (18)
12 (35)
Costa e Silva 1998
Venlafaxine 75-150mg
Fluoxetine 20-40mg / 196/n.m
186/n.m. / 8
Outpatients / 41 (11)
40 (10) / 80
77 / 30,4 (6,2)
29,7 (5,3) / 33,9 (6,0)
33,8 (5,6) / Experimental / n.m. / 29 (15)
18 (10)
Dierick 1996
Venlafaxine 75-150mg
Fluoxetine 20mg / 153/148
161/159 / 8
Outpatients / 44 (13)
43 (13) / 65
64 / 27,0 (4,2)
26,6 (4,1) / 30,6 (5,9)
30,1 (6,4) / Experimental / 112 / 38 (25)
40 (25)
McPartlin 1998
Venlafaxine 75 mg
Paroxetine 20 mg / 183/175
178/161 / 12
Outpatients / 45 (15)
44 (14) / 68
69 / 23 (4)
23 (4) / 29 (5)
29 (5) / Experimental / fixed / 47 (26)
52 (29)
Mehtonen 2000
Venlafaxine 75-150mg
Sertraline 50-100mg / 75/75
72/72 / 8
Outpatients / 44 (11)
41 (11) / 65
67 / 25,4 (3,5)c
25,8 (4,5)c / 27,8 (6,0)
28,1 (5,1) / Experimental / n.m. / 16 (21)
12 (17)
Montgomery 2004
Venlafaxine XR 75-150mg
Escitalopram 10-20mg / 145/142
148/146 / 8
Outpatients / 71 (17)
74 (19) / 71
73 / 20,4 (5,8)
19,9 (5,7) / 29,0 (5,4)
20,4 (5,8) / Comparator / 95 / 21 (14)d
23 (16)d
Nemeroff 2007
Venlafaxine 75-225 mg
Fluoxetine 20-60 mg
Placebo / 102/96
102/100
104/101 / 6
Outpatients / 40 (11)
38 (12)
40 (12) / 65
69
56 / 23,5 (3,2)c
23,7 (3,2)c
23,7 (3,3)c / 26,9 (5,3)
26,9 (4,5)
27,8 (5,1) / Experimental / 142 / (24)
(18)
(24)
Rudolph 1999
Venlafaxine 75-225mg
Fluoxetine 20-60 mg
Placebo / 100/95
103/103
98/97 / 8
Outpatients / 40 (n.m.)
40 (n.m.)
40 (n.m.) / 73
64
69 / 25 (20-38)c
26 (19-38)c
25 (20-34)c / 28 (10-43)
29 (15-43)
29 (15-45) / Experimental / 175 / (19)
(28)
(21)
Schatzberg 2006
Venlafaxine IR 75-225mg
Fluoxetine 20-60mg
Placebo / 104/93
100/99
96/96 / 8
Outpatients / 71
71
71 / 56
46
46 / 24 (n.m.)
24 (n.m.)
23 (n.m.) / 26 (n.m.)
27 (n.m.)
27 (n.m.) / Experimental / n.m. / (36)
(30)
(24)
Shelton 2006
Venlafaxin XR 75-225mg/d
Sertralin 50mg/d / 78/76
82/82 / 8
Outpatients / 37 (12)
41 (12) / 61
46 / 22,4 (2,9)
22,1 (2,9) / not applied / Comparator / n.m. / 11 (14)
19 (23)
Silverstone 1999
Venlafaxine 75-225mg
Fluoxetine 20-60mg
Placebo / 128/122
121/119
119/118 / 12
Outpatients / 41 (12)
43 (11)
42(11) / 64
60
58 / 27,6 (5,1)
27,0 (4,6)
27,1 (4,5) / not applied / Experimental / 141 / 37 (29)
32 (26)
48 (40)
Sir 2005
Venlafaxine XR 75-225mg
Sertraline 50-150mg / 84/84
79/79 / 8
Outpatients / 37 (12)
27 (14) / 67
72 / 23,5 (4,4)
23,4 (4,4) / not applied / Comparator / 161 / 25 (30)
13 (17)
Tylee 1997
Venlafaxine 75 mg
Fluoxetine 20 mg / 171/161
170/164 / 8
Outpatients / 44 (14)
46 (14) / 68
75 / 22,4 (5,0)c
22,5 (4,4)c / 27,8 (5,3)
29,3 (5,2) / Experimental / fixed / 47 (27)
46 (27)
Tzanakaki 2000
Venlafaxine 75-225mg
Fluoxetine 20-60mg / 55/55
54/54 / 6
Inpatients/
Day care / 47 (11)
49 (10) / 75
83 / 27,8 (5,6)c
27,1 (5,6)c / 36,4 (7,2)
37,0 (7,2) / Experimental / n.m. / 12 (22)
12 (22)
Abbreviations
f, female
N, number(s)
n.m., not mentioned
Notes
a: Number of all patients randomized/ all patients in ITT analysis for HAM-D or MADRS
b: mean (standard deviation)
c: HAMD21
d: Percentages calculated from numbers
e: Mean daily dosage at endpoint (mg) or mean daily dosage after last dosage increase

Table E 1 - Study characteristics and population of included studies

Regressand / Outcome
Remission / Response / Change-Score / Post-Score
b (95% CI) / p Value / b (95% CI) / p Value / b (95% CI) / p Value / b (95% CI) / p Value
Year / -0.00
(-0.03 to 0.02) / .742 / -0.01
(-0.02 to 0.00) / .101 / 0.02
(-0.00 to 0.04) / 0.096 / 0.01
(-0.01 to 0.02) / .523
Mean dosage / -0.00
(-0.00 to 0.00) / .732 / -0.00
(0.00to 0.00) / .921 / -0.00
(0,00to 0.00) / 0.870 / -0.00
(0,00to 0.00) / .600
Maximum allowed dosage / 0.00
(-0.00 to 0.00) / .690 / 0.00
(-0.00 to 0.00) / .463 / -0.00
(-0.00 to 0.00) / 0.537 / -0.00
(-0.00 to 0.00) / .363
b: point estimate of slope (log risk ratio)

Table E 2 - Regression analyses of publication year and maximum allowed dosage on outcome


RCT = randomized controlled trial, SSRI = selective serotonin reuptake inhibitor, TCA = tricyclic antidepressant.

Figure E1 - Included and Excluded Studies with Reasons According To the QUORUM Flow Diagram described in Moher et al. (1999



Figure E2 – Standardized mean differences in depression post scores, fixed effects model



Figure E3 – Mantel-Haenszel risk ratio for dropout, fixed effects model



Figure E4 – Mantel-Haenszel risk ratio for dropout due to adverse events, fixed effects model



Figure E5 – Regression of mean daily dosage on change score SMD