Table 10Summary of reported rates of response and remission for studies comparing monotherapy treatment to combined therapy

StudyDuration (Weeks)Rating Scalen*Comparison and Dose (mg/d)Responsea n (%)p ValueRemissionb n (%)p Value
Adding SSRI
Altamura 200882,835 dayHAMD-2118SSRI + PBO (saline)0 (0)<0.0001
18SSRI + CIT 10mg in 250ml of saline9 (50)NR
Adding Non-SSRI
Altamura 200882,835 dayHAMD-2118SSRI + PBO (saline)0 (0)<0.0001
18SSRI + CM 25mg in 250ml of saline (intravenous)11 (61.1)NR
Fava 200211812HAMD-1733FLX 40–60mg/d + PBO14 (42.4)0.2
34FLX 20mg/d, DES 25–50mg/d10 (29.4)
Fava 1994984HAMD-1715FLX 40–60mg/d8 (53)#0.24
12FLX 20mg + DES 25–50mg/d3 (25)#
Rush 20064412HAMD-17
QIDS-SR-16*
238SER 50–200mg/d63 (26.7)*NR42 (17.6)
63 (6.4)*
250VEN 37.5–375mg/d70 (28.2)*62 (24.8)
62 (24.8)*
239BUP 150–400mg/d62 (26.1)*51 (21.3)
61 (25.5)*
Trivedi 200611312HAMD-17
QIDS-SR-16*
279CIT + BUP, 200–400mg/d88 (31.8)*83 (29.7)
108 (38.7)*
0.93
0.16*
Preskorn 2008806HAMD-NS15PAX 40mg + PBO3 (20)<0.10
PAX 40mg + CP-101,606 infusion/duration to 1.5 hours and the dose to 0.5mg/kg per hour12 (80)
George 2008848HAMD-1710SSRI + PBO1 (10)0.15
11SSRI + ME, 5mg/d5 (45.4)
Adding Augmenting Agents
Michelson 200787,101,1328MPS74SER 100mg/d + PBO28 (37.8)0.865
72SER 100mg/d + AM 40mg/d29 (40.3)
Shapira 2006894HAMD-219SSRI + PBO7 (9)0.02
11SSRI + PI2 (11)
Seidman 2005916HAMD-2413SSRI + PBO volume matched, (injection)3 (23.1)0.226
13SSRI + TE 200–600mg/d7 (53.8)
Berman 20071098MADRS176New SSRI + PBONR for SSRI subgrupNR for SSRI subgroup
182New SSRI + ARI, 5–15NR for SSRI subgroupNR for SSRI subgroup
Marcus 2008105,1318MADRS191SSRI + PBONR for SSRI subgrupNR for SSRI subgrup
190SSRI + ARI 5–20mg/d (5–11mg ?)NR for SSRI subgroupNR for SSRI subgroup
Fava 20051148HAMD-17
CGI-I*
153SSRI + PBO48 (32)*>0.0955 (36)0.2
158SSRI + MOD 100–20064 (41)*68 (44)
Nemets 19991234HAMD 2418SSRI original dose + PBONR
18IN 12gm/d, SSRI original dose;NR
Dunner 2007868MADRS20SER 100–200mg/d4 (19)NS
21SER 100–200mg/d + ZI 40–80mg/d6 (32)
19SER 100–200mg/d + ZI 80–160mg/d2 (10)
Add Atypical Antipsychotics
Thase 2007888MADRS203FLX 50mg/d34 (16.7)
197OLZ 6–18mg/d29 (14.7)0.012
198OLZ 6–18mg/d + FLX50mg/d54 (27.3)0.003
Shelton 20011228MADRS8FLX 20–60mg/d1 (10)0.006 vs. com
8OLZ 5–20mg/d0 (0)0.003 vs. com
10OLZ 5–20mg/d, FLX 20–60mg/d6 (60)0.007
Mahmoud 20071086HAMD-1774SSRI + PBO18 (24.3)NR4 (5)NR
82SSRI + RIS 0.25–1mg/d37 (45.7021 (25)
Keitner 2009954MADRS22SSRI dose maintained + PBO5 (22.7)0.011
47RIS 0.5–3mg/d + antidepressant dose maintained24 (51)
Adding BUS
Rush 20064412HAMD-17
QIDS-SR-16*
238SER 50–200mg/d63 (26.7)*NR42 (17.6)
63 (6.4)*
250VEN 37.5–375mg/d70 (28.2)*62 (24.8) 62 (24.8)*
239BUP 150–400mg/d62 (26.1)*51 (21.3) 61 (25.5)*
Trivedi 200611312HAMD-17
QIDS-SR-16*
286CIT + BUS, 200–400mg/d77 (27)*86 (30.1) 94 (32.9)*0.93
0.16*
Appelberg 20011206MADRS51CIT 40mg/d/FLX 35.4mg/d + PBO16 (31)0.034
51CIT 40mg/d/FLX 35.4mg/d + BUS 35–47mg/d17 (33)
Landén 1998974CGI-S, CGI-I60CIT 46.1mg/d or PAX 39.8mg/d + PBO28 (46.7)NS
57CIT 46.1mg/d or PAX 39.8mg/d + BUS 49mg/d29 (50.9)
Adding Li
Fava 1994984HAMD-1715FLX 40–60mg/d8 (53)0.24
14FLX 20mg/d + LI 300–600mg/d4 (29)
Fava 200211812HAMD-1733FLX 40–60mg/d + PBO14 (42.4)0.2
34FLX 20mg/d, LI 300–600mg/d8 (23.5)
Baumann 19961244HAMD-2114CIT 40–60mg/d2 (14)0.05
10CIT 40–60mg/d, LI 800mg/d;6 (60)
Bondolfi 20061124MADRS19PAX 40mg/d2 (10.5)NR3 (15.7)NR
9VEN 150mg/d0 (0)0 (0)
13PAX 30mg/d + LI1 (7.8)0 (0)
Adding Pindolol
Perry 2004936HAMD17SSRI + PBO
FLX 20–60mg, PARO20–40mg, SER 50mg
6 (35.2)1
21SSRI + PI
Total = only SSRI doses given, PI dose not reported;
Group 1 = FLX 20–60mg, PAX 20mg, SER 150–200mg
5 (23.8)
Sokolski 2004964HAMD5PAX 40mg/d + PBONR0.001
4PAX 40mg/d + PI 7.5mg/d3 (75)
Adding MIN
Licht 20021196HAMD-NS99SER 100mg/d + PBO69 (70)0.6437 (38)0.38
98SER 200mg/d + PBO54 (64)0.0328 (29)0.19
98SER 100mg/d + MIN66 (67)43 (44)
Ferreri 20011216HAMD 1738FLX 20mg/d14 (37)0.114 (36)0.06
34MIN 60mg/d16 (48.5)6 (18)
32FLX 20mg/d + MIN 60–60mg/d20 (62.5)14 (44)
Adding Non-Pharmacological
Carta 200812732WHOQOL-Bref10SSRINRNR
20SSRI + ExerciseNRNR
Lynch 200712854HAMD-NS12SSRI6 (50)NR
20SSRI + DBT12 (60)
Wiles 20089416BDI9SSRI0
14SSRI + CBT8 (56)
Reynolds 201013710SCID/DSM-IV60SSRI + IPT49(82)0.2035(58)0.14
64SSRI49(77)29(45)
Rush 20064412HAMD-17
QIDS-SR-16*
238SER 50–200mg/d63 (26.7)*NR42 (17.6)
63 (6.4)*
250VEN 37.5–375mg/d70 (28.2)*62 (24.8) 62 (24.8)*
239BUP 150–400mg/d62 (26.1)*51 (21.3) 61 (25.5)*
36Medications Monotherapy8 (22.2)9 (25)
11 (30.5)
86CBT23 (26.7)24 (27.9)
24 (27.9)
65CIT + CBT23 (35.4)15 (23)
20 (20.7)

AM = atomoxetine; ARI = aripiprazole; BDI = Beck Depression Inventory; BUP = bupropion; BUS = buspirone; CBT = cognitive behavioral therapy; CGI-I = Clinical Global Impression – Improvement scale; CGI-S = Clinical Global Impression – Severity scale; CIT = citalopram; CM = clomipramine; DES = desipramine; DLX = duloxetine; FLX = fluoxetine; HAMD = Hamilton Depression Rating Scale; HAMD-NS = Hamilton Depression Rating Scale not specified; LI = lithium; MADRS = Montgomery-Åsberg Depression Rating Scale; ME = mecamyline hydrochloride; MIN = mianserin; MOD = modafinil; MPS = Maier Philipp core mood severity subscale; NR = not reported; NS = not significant; NT = not tested; OLZ = olanzapine; PAX = paroxetine; PBO = placebo; PI = pindolol; PLZ = phenelzine; QIDS-SR16 = Quick Inventory of Depressive Symptoms Self Report (16) RIS = risperidone; SER = sertraline; SSRI = selective serotonin reuptake inhibitors; TCP = tranylcypromine; TE = testosterone; VEN = venlafaxine; VEN-ER = venlafaxine extended release; WHOQOL-Bref = World Health Organization Quality of Life 26 item scale; ZI = ziprasidone

a

Response was defined as 50 percent change relative to baseline unless noted within the table.

b

Remission was defined as the standard threshold value for the particular outcome.

*

The QIDS-SR reported outcomes.

#

Response as a 30 percent change from baseline on the HAMD.

From: Results

Cover of Treatment for Depression After Unsatisfactory Response to SSRIs
Treatment for Depression After Unsatisfactory Response to SSRIs [Internet].
Comparative Effectiveness Reviews, No. 62.
Santaguida PL, MacQueen G, Keshavarz H, et al.

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