Table 4.
Efficacy and effectiveness of pharmacological, psychosocial and brain stimulation interventions vs. inactive control in children/adolescents with anxiety, obsessive‐compulsive, stress‐related, and mixed disorders
| Outcome | Intervention | Effect size (95% CI) | Control | Number of RCTs/patients | Q |
|---|---|---|---|---|---|
| Anxiety disorders | |||||
| Pharmacological interventions | |||||
|
Efficacy (clinician‐rated) |
Paroxetine | SMD=–0.43 (–0.75 to –0.10) | PBO/Sham | 14/2,502 | M |
| Fluvoxamine | SMD=–0.36 (–0.61 to –0.10) | PBO/Sham | 14/2,502 | M | |
| Imipramine | SMD=–0.27 (–0.92 to 0.39) | PBO/Sham | 14/2,502 | M | |
| Guanfacine | SMD=–0.13 (–0.39 to 0.12) | PBO/Sham | 14/2,502 | M | |
| Fluoxetine | SMD=–0.11 (–0.33 to 0.12) | PBO/Sham | 14/2,502 | M | |
| Atomoxetine | SMD=–0.11 (–0.38 to 0.16) | PBO/Sham | 14/2,502 | M | |
| Duloxetine | SMD=–0.09 (–0.27 to 0.09) | PBO/Sham | 14/2,502 | M | |
| Sertraline | SMD=–0.08 (–0.25 to 0.09) | PBO/Sham | 14/2,502 | M | |
| Venlafaxine | SMD=–0.06 (–0.22 to 0.04) | PBO/Sham | 14/2,502 | M | |
| Efficacy (subject‐rated) | Fluoxetine | SMD=–0.51 (–0.85 to –0.18) | PBO/Sham | 2/154 | M |
| SNRIs | SMD=–2.14 (–9.75 to 5.48) | PBO/Sham | 3/622 | M | |
| Venlafaxine | SMD=–1.71 (–3.93 to 0.51) | PBO/Sham | 2/443 | M | |
| SSRIs | SMD=–0.42 (–0.96 to 0.12) | PBO/Sham | 4/197 | M | |
| Atomoxetine | SMD=–0.29 (–0.51 to 0.08) | PBO/Sham | 2/331 | M | |
| TCAs | SMD= 0.36 (–0.27 to 0.99) | PBO/Sham | 2/41 | M | |
| Efficacy (parent‐rated) | SSRIs | SMD=–0.82 (–1.38 to –0.27) | PBO/Sham | 2/96 | L |
| Response | Fluvoxamine | OR=8.17 (1.35‐49.40) | PBO/Sham | 19/2,656 | M |
| Sertraline | OR=6.05 (2.23‐49.40) | PBO/Sham | 19/2,656 | M | |
| Fluoxetine | OR=4.06 (1.49‐18.17) | PBO/Sham | 19/2,656 | M | |
| Guanfacine | OR=5.47 (0.74‐49.40) | PBO/Sham | 19/2,656 | M | |
| Atomoxetine | OR=4.06 (0.67‐24.53) | PBO/Sham | 19/2,656 | M | |
| Paroxetine | OR=3.67 (0.67‐20.09) | PBO/Sham | 19/2,656 | M | |
| Imipramine | OR=3.00 (0.61‐14.88) | PBO/Sham | 19/2,656 | M | |
| Venlafaxine | OR=2.46 (0.90‐6.69) | PBO/Sham | 19/2,656 | M | |
| Duloxetine | OR=2.01 (0.37‐11.02) | PBO/Sham | 19/2,656 | M | |
| Clomipramine | OR=1.22 (0.22‐6.69) | PBO/Sham | 19/2,656 | M | |
| Acceptability | Clomipramine | OR=0.55 (0.02‐7.39) | PBO/Sham | 20/2,679 | M |
| Paroxetine | OR=0.61 (0.12‐3.32) | PBO/Sham | 20/2,679 | M | |
| Fluvoxamine | OR=0.67 (0.11‐4.06) | PBO/Sham | 20/2,679 | M | |
| Sertraline | OR=0.67 (0.14‐2.72) | PBO/Sham | 20/2,679 | M | |
| Guanfacine | OR=0.67 (0.10‐4.95) | PBO/Sham | 20/2,679 | M | |
| Atomoxetine | OR=0.82 (0.15‐4.95) | PBO/Sham | 20/2,679 | M | |
| Duloxetine | OR=1.00 (0.18‐5.47) | PBO/Sham | 20/2,679 | M | |
| Venlafaxine | OR=1.11 (0.33‐3.67) | PBO/Sham | 20/2,679 | M | |
| Fluoxetine | OR=1.65 (0.50‐6.69) | PBO/Sham | 20/2,679 | M | |
| Imipramine | OR=2.01 (0.37‐9.97) | PBO/Sham | 20/2,679 | M | |
| Remission | Fluoxetine | RR=2.52 (1.19‐5.32) | PBO/Sham | 2/95 | L |
|
Suicide attempt/ ideation |
Sertraline | LogOR=–19.8 (–61.7 to 0.7) | PBO/Sham | 9/1,648 | M |
| Duloxetine | LogOR=0.2 (–2.5 to 2.8) | PBO/Sham | 9/1,648 | M | |
| Venlafaxine | LogOR=1.4 (–1.4 to 5.24) | PBO/Sham | 9/1,648 | M | |
| Atomoxetine | LogOR=6.6 (–31.6 to 22.7) | PBO/Sham | 9/1,648 | M | |
| Guanfacine | LogOR=16.1 (–1.0 to 58.3) | PBO/Sham | 9/1,648 | M | |
| Imipramine | LogOR=17.3 (–0.1 to 54.8) | PBO/Sham | 9/1,648 | M | |
| Paroxetine | LogOR=20.0 (1.7 to 60.47) | PBO/Sham | 9/1,648 | M | |
| Tolerability | Venlafaxine | LogOR=–0.8 (–3.8 to 2.1) | PBO/Sham | 15/2,516 | M |
| Atomoxetine | LogOR=0.0 (–5.3 to 5.3) | PBO/Sham | 15/2,516 | M | |
| Duloxetine | LogOR=0.2 (–3.9 to 4.3) | PBO/Sham | 15/2,516 | M | |
| Sertraline | LogOR=1.7 (–2.8 to 6.6) | PBO/Sham | 15/2,516 | M | |
| Paroxetine | LogOR=1.7 (–2.5 to 6.0) | PBO/Sham | 15/2,516 | M | |
| Fluovoxamine | LogOR=2.1 (–2.4 to 7.0) | PBO/Sham | 15/2,516 | M | |
| Fluoxetine | LogOR=2.5 (–1.8 to 7.9) | PBO/Sham | 15/2,516 | M | |
| Imipramine | LogOR=16.6 (–37.5 to 83.7) | PBO/Sham | 15/2,516 | M | |
| Guanfacine | LogOR=29.2 (2.2‐94.3) | PBO/Sham | 15/2,516 | M | |
| Psychosocial interventions | |||||
|
Efficacy (clinician ‐rated) |
CBT/BT | SMD=–0.85 (–1.12 to –0.57) | WL/NT | 7/358 | L |
| Efficacy (subject‐rated) | CBT‐Child only | SMD=–1.04 (–1.41 to –0.67) | WL/NT | 24/1,239 | L |
| CBT‐Group | SMD=–0.91 (–1.22 to –0.60) | WL/NT | 27/1,268 | L | |
| CBT | SMD=–0.67 (–0.88 to –0.47) | WL/NT | 45/2,831 | L | |
| CBT‐Child+P | SMD=–0.45 (–0.67 to –0.23) | WL/NT | 20/1,285 | L | |
| CBT‐Individual | SMD=–0.39 (–0.64 to –0.15) | WL/NT | 21/1,203 | L | |
| CBT | SMD=–0.31 (–0.51 to –0.11) | PBO/Sham | 15/978 | L | |
| CBT‐Parent only | SMD=0.04 (–0.38 to 0.46) | WL/NT | 5/307 | L | |
| Efficacy (parent‐rated) | CBT‐Group | SMD=–0.92 (–1.21 to –0.62) | WL/NT | 21/1,279 | L |
| CBT‐Child only | SMD=–0.87 (–1.21 to –0.53) | WL/NT | 13/734 | L | |
| CBT | SMD=–0.70 (–0.90 to –0.51) | WL/NT | 35/2137 | L | |
| CBT‐Child+P | SMD=–0.69 (–0.98 to –0.39) | WL/NT | 17/1,031 | L | |
| CBT‐Individual | SMD=–0.43 (–0.65 to –0.21) | WL/NT | 17/858 | L | |
| CBT‐Parent only | SMD=–0.37 (–0.77 to 0.04) | WL/NT | 5/372 | L | |
| CBT | SMD=–0.25 (–0.61 to 0.11) | PBO/Sham | 8/638 | L | |
| Efficacy (mixed‐rated) | BT‐Group | SMD=–1.43 (–2.36 to –0.51) | WL/NT | 101/6,625 | L |
| CBT‐Group | SMD=–1.43 (–1.76 to –1.09) | WL/NT | 101/6,625 | L | |
| BT‐Individual+P | SMD=–1.09 (–1.93 to –0.25) | WL/NT | 101/6,625 | L | |
| CBT‐Group+P | SMD=–0.99 (–1.31 to –0.68) | WL/NT | 101/6,625 | L | |
| CBT‐Individual | SMD=–0.99 (–1.30 to –0.68) | WL/NT | 101/6,625 | L | |
| CBT‐Individual+P | SMD=–0.84 (–1.16 to –0.53) | WL/NT | 101/6,625 | L | |
| CBT‐Group | SMD=–0.76 (–1.16 to –0.36) | PBO/Sham | 101/6,625 | L | |
| CBT‐Parent only | SMD=–0.70 (–1.22 to –0.19) | WL/NT | 101/6,625 | L | |
| CBT‐Internet | SMD=–0.61 (–1.02 to –0.20) | WL/NT | 101/6,625 | L | |
| BT‐Individual+Group | SMD=–0.73 (–1.59 to 0.13) | WL/NT | 101/6,625 | L | |
| CBT‐Individual+Group | SMD=–0.64 (–1.69 to 0.41) | WL/NT | 101/6,625 | L | |
| BT‐Individual+P | SMD=–0.42 (–1.29 to 0.44) | PBO/Sham | 101/6,625 | L | |
| CBT‐Group+P | SMD=–0.33 (–0.78 to 0.13) | PBO/Sham | 101/6,625 | L | |
| CBT‐Individual | SMD=–0.32 (–0.72 to 0.07) | PBO/Sham | 101/6,625 | L | |
| CBT‐Individual+P | SMD=–0.18 (–0.61 to 0.25) | PBO/Sham | 101/6,625 | L | |
| BT‐Individual+Group | SMD=–0.06 (–0.94 to 0.82) | PBO/Sham | 101/6,625 | L | |
| CBT‐Internet | SMD=0.06 (–0.48 to 0.60) | PBO/Sham | 101/6,625 | L | |
| Acceptability | CBT‐Individual+Group | OR=0.26 (0.05‐5.73) | WL/NT | 101/6,625 | L |
| BT‐Individual+P | OR=0.64 (0.22‐2.72) | WL/NT | 101/6,625 | L | |
| BT‐Individual+P | OR=0.81 (0.19‐2.27) | PBO/Sham | 101/6,625 | L | |
| CBT‐Group+P | OR=0.90 (0.46‐1.60) | PBO/Sham | 101/6,625 | L | |
| CBT‐Group | OR=0.85 (0.46‐1.44) | PBO/Sham | 101/6,625 | L | |
| BT | OR=0.90 (0.32‐3.95) | WL/NT | 101/6,625 | M | |
| CBT‐Individual | OR=0.92 (0.52‐1.52) | PBO/Sham | 101/6,625 | L | |
| CBT‐Group | OR=0.93 (0.57‐1.63) | WL/NT | 101/6,625 | L | |
| CBT | OR=1.09 (0.85‐1.41) | WL/NT | 45/3,158 | L | |
| CBT‐Group+P | OR=0.99 (0.67‐1.55) | WL/NT | 101/6,625 | M | |
| CBT | OR=1.00 (0.68‐1.49) | PBO/Sham | 12/797 | L | |
| CBT‐Internet | OR=1.02 (0.42‐2.08) | PBO/Sham | 101/6,625 | L | |
| CBT‐Individual | OR=1.02 (0.67‐1.67) | WL/NT | 101/6,625 | L | |
| CBT‐Internet | OR=1.05 (0.59‐2.05) | WL/NT | 101/6,625 | L | |
| CBT‐Individual+P | OR=1.11 (0.60‐1.90) | PBO/Sham | 101/6,625 | L | |
| BT‐Individual+Group | OR=1.13 (0.28‐3.19) | PBO/Sham | 101/6,625 | L | |
| BT‐Group | OR=1.21 (0.27‐22.51) | WL/NT | 101/6,625 | L | |
| CBT‐Individual+P | OR=1.23 (0.80‐2.02) | WL/NT | 101/6,625 | L | |
| CBT‐Parent only | OR=1.43 (0.75‐3.15) | WL/NT | 101/6,625 | L | |
| Depressive symptoms | CBT | SMD=–0.34 (–0.51 to –0.17) | WL/NT | 17/1,157 | L |
| CBT | SMD=–0.18 (–0.45 to 0.09) | PBO/Sham | 10/613 | L | |
| Functioning | CBT | SMD=–1.03 (–1.38 to –0.68) | WL/NT | 11/557 | L |
| Quality of life | CBT‐Parent only | SMD=–1.87 (–3.04 to –0.71) | WL/NT | 101/6,625 | L |
| CBT‐Individual | SMD=–1.13 (–1.82 to –0.45) | PBO/Sham | 101/6,625 | L | |
| CBT‐Individual | SMD=–1.01 (–1.55 to –0.48) | WL/NT | 101/6,625 | L | |
| CBT‐Internet | SMD=–0.86 (–1.57 to –0.15) | PBO/Sham | 101/6,625 | L | |
| CBT‐Group | SMD=–0.85 (–1.45 to –0.26) | PBO/Sham | 101/6,625 | L | |
| CBT‐Individual+P | SMD=–0.80 (–1.33 to –0.27) | WL/NT | 101/6,625 | L | |
| CBT‐Group+P | SMD=–0.75 (–1.34 to –0.17) | WL/NT | 101/6,625 | L | |
| CBT‐Group | SMD=–0.73 (–1.34 to –0.11) | WL/NT | 101/6,625 | L | |
| CBT‐Internet | SMD=–0.73 (–1.14 to –0.33) | PBO/Sham | 101/6,625 | L | |
| BT‐Individual+Group | SMD=–0.79 (–1.68 to 0.09) | WL/NT | 101/6,625 | L | |
| BT‐Individual+Group | SMD=–0.67 (–1.56 to 0.21) | WL/NT | 101/6,625 | L | |
| CBT‐Individual+Group | SMD=–0.55 (–1.78 to 0.69) | WL/NT | 101/6,625 | L | |
| Remission | CBT‐Child only | OR=10.42 (5.84‐7.60) | WL/NT | 19/1,184 | M |
| CBT‐Group | OR=6.25 (4.45‐8.78) | WL/NT | 25/1,532 | M | |
| CBT‐Remote | OR=6.14 (2.97‐12.71) | WL/NT | 10/591 | L | |
| CBT | OR=5.45 (3.90‐7.60) | WL/NT | 39/2,697 | L | |
| CBT‐Individual | OR=4.53 (2.55‐8.03) | WL/NT | 17/1,165 | L | |
| CBT‐Individual+P | OR=4.08 (2.72‐6.11) | WL/NT | 19/1,142 | M | |
| CBT‐Child only | OR=3.58 (1.92‐6.65) | PBO/Sham | 7/509 | L | |
| CBT‐Group | OR=3.10 (1.14‐8.45) | PBO/Sham | 5/353 | L | |
| CBT‐Parent only | OR=2.83 (1.12‐7.16) | WL/NT | 4/371 | L | |
| CBT | OR=2.28 (1.33‐3.89) | PBO/Sham | 10/822 | L | |
| CBT‐Individual | OR=2.04 (1.06‐3.91) | PBO/Sham | 5/469 | L | |
| CBT‐Individual+P | OR=1.12 (0.65‐1.92) | PBO/Sham | 4/313 | L | |
| Social anxiety disorder | |||||
| Efficacy (subject‐rated) | CBT | SMD=–1.59 (–2.33 to –0.86) | WL/NT | 11/603 | L |
| BT | SMD=–1.22 (–2.06 to –0.38) | WL/NT/PBO/Sham | 4/169 | L | |
| CBT | SMD=–1.19 (–1.72 to –0.67) | WL/NT/PBO/Sham | 14/872 | L | |
| CBT‐Group | SMD=–1.19 (–1.93 to –0.45) | WL/NT/PBO/Sham | 11/670 | L | |
| CBT/BT | SMD=–1.13 (–1.59 to –0.68) | WL/NT/PBO/Sham | 17/1,016 | L | |
| CBT+P | SMD=–1.13 (–1.59 to –0.67) | WL/NT/PBO/Sham | 17/983 | L | |
| CBT‐Individual | SMD=–1.10 (–1.91 to –0.29) | WL/NT/PBO/Sham | 3/127 | L | |
| CBT‐Individual+Group | SMD=–0.80 (–1.19 to –0.41) | WL/NT/PBO/Sham | 3/115 | L | |
| CBT‐Child only | SMD=–0.75 (–1.24 to –0.26) | WL/NT/PBO/Sham | 2/70 | L | |
| CBT‐Internet | SMD=–0.52 (–1.01 to –0.03) | WL/NT/PBO/Sham | 2/143 | L | |
| Acceptability | CBT | RR=1.00 (0.72‐1.41) | WL/NT/PBO/Sham | 16/1,052 | M |
| Depressive symptoms | CBT/BT | SMD=–0.39 (–0.63 to –0.16) | WL/NT/PBO/Sham | 8/299 | L |
| Quality of life | CBT/BT | SMD=–0.79 (–1.17 to –0.41) | WL/NT/PBO/Sham | 9/552 | L |
| Remission | CBT/BT | RR=8.99 (5.27‐15.33) | WL/NT/PBO/Sham | 13/832 | L |
| Obsessive‐compulsive disorder | |||||
| Pharmacological interventions | |||||
|
Efficacy (clinician‐rated) |
Sertraline | SMD=–0.24 (–0.46 to –0.03) | PBO/Sham | 17/991 | L |
| Fluoxetine | SMD=–0.24 (–0.47 to –0.01) | PBO/Sham | 17/991 | L | |
| Clomipramine | SMD=–0.31 (–0.64 to 0.02) | PBO/Sham | 17/991 | L | |
| Fluvoxamine | SMD=–0.21 (–0.49 to 0.06) | PBO/Sham | 17/991 | L | |
| Response | Fluoxetine | RR=1.49 (1.15‐1.96) | PBO/Sham | 2/146 | L |
| SSRI/TCAs | RR=1.80 (1.43‐2.26) | PBO/Sham | 7/692 | L | |
| Acceptability | Fluoxetine | MOR=0.74 (0.25‐1.68) | PBO/Sham | 18/1,143 | L |
| Fluvoxamine | MOR=0.79 (0.24‐2.07) | PBO/Sham | 18/1,143 | L | |
| Sertraline | MOR=0.89 (0.32‐2.07) | PBO/Sham | 18/1,143 | L | |
| Paroxetine | MOR=1.12 (0.37‐3.42) | PBO/Sham | 18/1,143 | L | |
| Clomipramine | MOR=3.06 (0.54‐21.69) | PBO/Sham | 18/1,143 | L | |
| Tolerability | SSRIs | RR=3.59 (1.89‐6.84) | PBO/Sham | 7/807 | L |
| Global illness severity | Fluoxetine | SMD=–0.52 (–0.86 to –0.18) | PBO/Sham | 2/146 | L |
| SSRIs | SMD=–0.42 (–0.61 to –0.23) | PBO/Sham | 5/556 | M | |
| Remission | SSRIs | RR=2.06 (1.03‐4.13) | PBO/Sham | 3/302 | L |
| Pharmacological augmentation (in SSRI‐refractory cases) | |||||
| Response | Risperidone | OR=6.35 (1.48‐27.3) | PBO/Sham | 3/72 | M |
| Quetiapine | OR=2.33 (0.88‐6.20) | PBO/Sham | 3/102 | M | |
| Olanzapine | OR=2.74 (0.34‐21.9) | PBO/Sham | 2/70 | L | |
| Psychosocial interventions | |||||
|
Efficacy (clinician‐rated) |
CBT | SMD=–0.78 (–1.05 to –0.51) | WL/NT | 17/991 | L |
| BT | SMD=–0.72 (–1.20 to –0.24) | WL/NT | 17/991 | L | |
| CBT | SMD=–0.23 (–0.56 to 0.11) | PBO/Sham | 17/991 | L | |
| Response | CBT/BT‐ERP | RR=3.93 (2.52‐6.14) | WL/NT/PBO/Sham | 6/236 | L |
| Acceptability | CBT | MOR=0.49 (0.09‐2.40) | PBO/Sham | 18/1,143 | L |
| BT‐ERP | RR=0.80 (0.35‐1.84) | PBO/WL | 6/301 | L | |
| CBT | MOR=0.86 (0.23‐3.24) | PBO/Sham | 18/1,143 | L | |
| CBT | MOR=0.94 (0.21‐4.79) | WL/NT | 18/1,143 | L | |
| BT | MOR=14.28 (0.87‐785.20) | WL/NT | 18/1,143 | L | |
| Functioning (subject‐rated) | CBT | SMD=–1.15 (–2.11 to –0.19) | WL/NT | 3/194 | L |
| Functioning (parent‐rated) | CBT | SMD=–0.95 (–1.61 to –0.28) | WL/NT | 3/194 | L |
| CBT | SMD=–0.31 (–0.63 to 0.01) | PBO/Sham | 2/183 | L | |
| Remission | CBT | RR=2.33 (1.33‐4.00) | WL/NT | 4/271 | L |
| CBT | RR=1.59 (1.28‐1.96) | PBO/Sham | 3/153 | L | |
| Quality of life | CBT | SMD=–0.39 (–0.77 to –0.02) | WL/PBO/Sham | 2/223 | L |
| Combined interventions | |||||
| Efficacy | CBT+sertraline | SMD=–0.58 (–0.91 to –0.25) | PBO/Sham | 17/991 | L |
| Acceptability | CBT+sertraline | MOR=0.54 (0.08‐3.15) | PBO/Sham | 18/1,143 | L |
| Post‐traumatic stress disorder | |||||
| Efficacy | CBT | SMD=–1.34 (–1.79 to –0.89) | WL/NT | 3/98 | L |
| EMDR | SMD=–0.61 (–1.96 to 0.74) | WL/NT | 2/65 | L | |
| NET | SMD=–0.57 (–1.23 to 0.09) | WL/NT | 2/79 | L | |
| Response | CBT | OR=8.64 (2.01‐37.14) | WL/NT | 2/49 | L |
| NET | OR=3.82 (0.67‐21.8) | WL/NT | 2/78 | L | |
| Acceptability | NET | OR=5.13 (0.56‐47.28) | WL/NT | 2/83 | L |
| Anxiety symptoms | NET | SMD=–0.66 (–1.33 to 0.01) | WL/NT | 2/59 | L |
| Depressive symptoms | CBT | SMD=–0.8 (–1.47 to –0.131) | WL/NT | 3/98 | L |
| Enuresis | |||||
| Pharmacological interventions | |||||
| Efficacy | Imipramine | SMD=–0.46 (–0.67 to –0.24) | PBO/Sham | 4/347 | M |
| Response | Amitriptyline | RR=1.22 (1.02‐1.45) | PBO/Sham | 2/98 | L |
| Imipramine | RR=1.35 (1.11‐1.64) | PBO/Sham | 12/831 | L | |
|
Psychosocial interventions | |||||
| Efficacy | BT‐Alarm | SMD=–1.30 (–2.16 to –0.44) | WL/NT | 4/127 | L |
| Response | BT‐Alarm | RR=7.23 (1.40‐37.77) | WL/NT | 18/827 | L |
| BT‐Alarm | RR=1.59 (1.16‐2.17) | PBO/Sham | 2/181 | L | |
| BT‐Reward | RR=1.22 (1.03‐1.45) | WL/NT | 2/325 | L | |
RCTs – randomized controlled trials, SMD – standardized mean difference, OR – odds ratio, MOR – median odds ratio, RR – risk ratio, PBO – placebo, WL – waiting list, NT – no treatment, Q – quality (H – high, M – medium, L – low), BT – behavioral therapy, BT‐ERP – behavioral therapy with exposure and response prevention, CBT – cognitive behavioral therapy, EMDR – eye movement desensitization and reprocessing, NET – narrative exposure therapy, P – parental involvement, SSRIs – selective serotonin reuptake inhibitors, SNRIs – serotonin‐norepinephrine reuptake inhibitors, TCAs – tricyclic antidepressants. Bold prints indicate significant values. SMDs<0 indicate that intervention is more effective than control. For discontinuation outcomes (acceptability, tolerability, inefficacy) and relapse, OR/RR<1 favors the intervention. For response and remission, OR/RR>1 favors the intervention.