Table 29Summary of reported rates of harms for studies comparing monotherapy to combined therapies

StudyDuration (Weeks)n*Comparison and Dose (mg/d)Anxiety n (%)Sedation n (%)GI Problems n (%)Sleep Problems n (%)Weight Gain n (%)Head-ache (n (%)Sexual Dysfunction n (%)Withdrawals Due To A/E n (%)Serious Events n (%)Suicide n (%)
Adding SSRI
Altamura82,83 20085 days18SSRI + PBO (saline)03 (18.2)2 (11.1)0NR0NR7 (39)NRNR
18SSRI + CIT 10mg in 250ml of saline2 (11.1)003 (16.7)NR1 (5.6)NR9 (50)NRNR
Adding Non-SSRI Antidepressants
Altamura82,83 20085 days18SSRI + PBO (saline)NR3 (18.2)2 (11.1)NRNRNRNR7 (39)NRNR
18SSRI + CM 25mg in 250ml of saline (intravenous)NR4 (22.2)5 (27.8)NRNRNRNR13 (72)NRNR
Fava118 20021233FLX 40–60mg/d + PBO06 (18.2)18 (54.5)NRNR14 (42.5)NRNRNRNR
34FLX 20mg/d, DES 25–50mg/d10 (39.4)9 (26.5)6 (47.1)NRNR0NRNRNRNR
Fava98 1994415FLX 40–60mg/d0NRNRNRNRNRNRNRNRNR
12FLX 20mg + DES 25–50mg/d1 (8)NRNRNRNRNRNRNRNRNR
Rush44 200612238SER 50–200mg/dNRNRNRNRNRNRNRNR11 (4.6)2 (0.84)
250VEN 37.5–375mg/dNRNRNRNRNRNRNRNR5 (2)0
239BUP 150–400mg/dNRNRNRNRNRNRNRNR6 (2.5)2 (0.83)
Trivedi113 200612279CIT + BUP, 200–400mg/dNRNRNRNRNRNRNR10 (3.6)11 (3.9)1 (0.36)
Augmenting Agents
Preskorn80 2008615PAX 40mg + PBONRNRNRNRNRNRNR2 (13)NRNR
15PAX 40mg + CP-101606 infusion/ duration to 1.5h and the dose to 0.5mg/kg/hNRNRNRNRNRNRNR6 (40)NRNR
George84 2008810SSRI + PBONRNR6 (60)NRNRNR1 (10)NRNRNR
11SSRI + Mecamylamine Hydrochloride, 5mg/dNRNR10 (91)NRNRNR5 (45)NRNRNR
Michelson87,101,132 2007874SER 100mg/d + PBO0/74NR12 (16)1 (1.3)NR6 (8)NRNRNRNR
72SER 100mg/d + AM 40mg/d4 (5.6)NR18 (25)8 (11)NR4 (5.6)NRNRNRNR
Shapira89 200649SSRI + PBO1 (11.1)NRNRNRNRNRNRNR00
11SSRI + PHN1 (1.11)NRNRNRNRNRNRNR1 (1.11)1 (1.11)
Seidman91 2005613SSRI + PBO volume matched (injection)NRNRNRNRNRNRNRNRNRNR
13SSRI + TE 200–600mg/dNRNRNRNRNRNRNRNRNRNR
Fava114 20058153SSRI + PBONRNR13 (9)7 (5)NRNRNRNRNRNR
158SSRI + MOD 100–200NRNR21 (13)7 (4)NRNRNRNRNRNR
Nemets123 1999418SSRI original dose + PBONRNR1/19 (5.2)NRNRNRNR1 (5.5)NRNR
18IN 12gm/d, SSRI original doseNRNR1/23 (43)NRNRNRNR2 (11.1)NRNR
Dunner86 2007820SER 100–200mg/d02 (10001 (5)NR1 (5)NR8 (40)NRNR
21SER 100–200 mg/d + ZI 40–80mg/d5 (22.7)5 (22.7)4 (18.108 (36.4)NR4 (18.2)NR21 (100)NRNR
19SER 100–200 mg/d + ZI 80–160mg/d3 (26.3)3 (15.8)5 (26.4)6 (31.6)NR3 (15.8)NR16 (84)NRNR
Adding Atypical Antipsychotics
Thase88 20078203FLX 50mg/dNR(5.3)NR(2.4)(6.8)(19.4)NRNR0NR
197OLZ 6–18mg/dNR(12.1)NR(11.1)(39.7)(13.1)NRNR0NR
198OLZ 6–18mg/d + FLX 50mg/dNR(17.5)NR(10.5)(35)(2.5)NRNR2 (1)NR
Shelton122 200188FLX 20–60mg/dNRNRNRNRNRNRNR0NRNR
8OLZ 5–20mg/dNRNRNRNRNRNRNR1 (12.5)NRNR
10OLZ 5–20mg/d, FLX 20–60mg/dNRNRNRNRNRNRNR0NRNR
Adding BUS
Rush44 200612238SER 50–200mg/dNRNRNRNRNRNRNRNR11 (4.6)2 (0.84)
250VEN 37.5–375mg/dNRNRNRNRNRNRNRNR5 (2)0
239BUP 150–400mg/dNRNRNRNRNRNRNRNR6 (2.5)2 (0.83)
Trivedi113 200612286CIT + BUS, 200–400mg/dNRNRNRNRNRNRNR12 (4.2)12 (4)4 (1.4)
Appelberg120 2001651CIT 40mg/d/FLX 35.4mg/d + PBONRNRNRNRNRNRNRNRNRNR
51CIT 40mg/d/FLX 35.4mg/d + BUS 35–47mg/dNRNRNRNRNRNRNRNRNRNR
Landén92,97,130 1998460CIT 46.1mg/d or PAX 39.8mg/d + PBONR30 (58)NRNRNR23 (44)NR$NRNRNR
57CIT 46.1mg/d or PAX 39.8mg/d + BUS 49mg/dNR29 (48)NRNRNR23 (38)NR#NRNRNR
Adding Li
Fava98 1994415FLX 40–60mg/dNRNRNRNRNRNRNRNRNRNR
14FLX 20mg/d + LI 300–600mg/dNRNRNRNRNRNRNRNRNRNR
Fava118 20021233FLX 40–60mg/d + PBONR6 (18.2)18 (54.5)NRNR14 (42.5)NRNRNRNR
34FLX 20mg/d, LI 300–600mg/dNR11 (32.4)17 (50)NRNR9 (26.5)NRNRNRNR
Baumann124 1996414CIT 40–60mg/dNRNRNRNRNRNRNRNRNRNR
10CIT 40–60mg/d, LI 800mg/dNRNRNRNRNRNRNRNRNRNR
Bondolfi112 2006419PAX 40mg/d;NRNRNRNRNRNRNRNRNRNR
9VEN 150mg/dNRNRNRNRNRNRNRNRNRNR
13PAX 30mg/d + LI;NRNRNRNRNRNRNRNRNRNR
Adding Pindolol
Perry93 2004617SSRI + PBO
FLX 20–60mg, PAX 20–40mg, SER 50mg
NRNRNRNRNRNRNRNRNRNR
21SSRI + PI
Total = only SSRI doses given, PI dose not reported; Group 1 = FLX 20–60mg, PAX 20mg, SER 150–200mg;
NRNRNRNRNRNRNRNRNRNR
Sokolski96 200445PAX 40mg/d + PBONRNRNRNRNRNRNRNRNRNR
4PAX 40mg/d + PI 7.5mg/dNRNRNRNRNRNRNR2 (50)NRNR
Adding MIN
Licht119 2002699SER 100mg/d + PBONR12 (12.2)16 (16.4)4 (4.1)3 (3.1)2 (2)NR45 (45)NRNR
98SER 200mg/d + PBONR16 (16.3)16 (16.3)10 (10.2)2 (2)7 (7.1)NR54 (55)NRNR
98SER 100mg/d + MINNR45 (45.9)13 (13.2)9 (9.2)8 (8.2)5 (5.1)NR75 (77)NRNR
Ferreri121 2001638FLX 20mg/dNR00NR03 (7.8)NR8 (21)NRNR
34MIN 60mg/dNR5 (14.7)3 (8.3)NR2 (5.8)2 (5.8)NR0NRNR
32FLX 20mg/d + MIN 60-60mg/dNR3 (9.8)1 (3.1)NR5 (15.8)0NR2 (6.3)NRNR
Adding Nonpharmacological
Carta127 20083210SSRINRNRNRNRNRNRNRNRNRNR
20SSRI + ExerciseNRNRNRNRNRNRNRNRNRNR
Lynch128 20075412SSRINRNRNRNRNRNRNRNRNRNR
20SSRI + DBTNRNRNRNRNRNRNRNRNRNR
Wiles94 2008169SSRINRNRNRNRNRNRNRNRNRNR
14SSRI + CBTNRNRNRNRNRNRNRNRNRNR
Rush44 200612238SER 50–200mg/dNRNRNRNRNRNRNRNR11 (4.6)2 (0.84)
250VEN 37.5–375mg/dNRNRNRNRNRNRNRNR5 (2)0
239BUP 150–400mg/dNRNRNRNRNRNRNRNR6 (2.5)2 (0.83)
Thase110 20071286Medications MonotherapyNRNRNRNRNRNRNR23* (27, 652, 75306)2^NR
36CBTNRNRNRNRNRNRNR6 (17)0^NR
65CIT + CBTNRNRNRNRNRNRNR6 (9)4^NR
117Combined medicationsNRNRNRNRNRNRNR22 (19)4^NR

A/E = adverse event; BUP = bupropion; BUS = buspirone; CM = clomipramine; CIT = citalopram; CBT = cognitive behavioral therapy; DBT = dialectical behavior therapy; DES = desipramine; FLX = fluoxetine; GI = gastrointestinal; IN = inositol; LI = lithium; MIN = mianserin; MOD = modafinil; n = sample size; NR = not reported; OLZ = olanzapine; PAX = paroxetine; PBO = placebo; PHN = Phenytoin; PI = pindolol; SER = sertraline; SSRI = selective serotonin reuptake inhibitors; TE = testosterone; VEN = venlafaxine; ZI = ziprasidone

*

Exited because of intolerance.

At least one serious event and includes a combination of events requiring hospitalization for psychiatric event (including for suicidal ideation), death or medical event.

#

Indicates the patients reporting remittance from sexual dysfunction at 4 weeks (n=47) but not proportion that had dysfunction with the use of buspirone.

$

Reported only baseline prevalence of sexual dysfunction.

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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