Summary of findings 2. DCS and cognitive and behavioural therapies compared to placebo and cognitive and behavioural therapies for anxiety disorders in children and adolescents.
| Augmentation of cognitive and behavioural therapies with DCS compared to placebo for anxiety disorders in children and adolescents at end of treatment | ||||||
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Patient or population: Children and adolescents with anxiety disorders
Settings: Outpatient settings in Australia, the UK and the USA
Intervention: Augmentation of cognitive and behavioural therapies with DCS Comparison: Cognitive and behavioural therapies and placebo pill | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo and cognitive and behavioural therapies | DCS and cognitive and behavioural therapies | |||||
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Treatment efficacy: treatment responders As assessed per study |
77 per 100 | 78 per 100 (60 to 100) | RR 1.01 (0.78 to 1.31) | 121 participants (4 studies) | ⊕⊕⊝⊝ low1 | Subgroups included OCD (3 studies) and PTSD (1) |
| Treatment acceptability: withdrawals from treatment | 9 per 100 | 8 per 100 (2 to 43) | RR 0.90 (0.17 to 4.69) | 131 participants (4 studies) | ⊕⊝⊝⊝ very low1,2 | Subgroups included OCD (3) and PTSD (1) |
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In remission As assessed per study |
45 per 100 | 54 per 100 (30 to 98) | RR 1.19 (0.66 to 2.16) | 44 participants (2 studies) | ⊕⊕⊝⊝ low1 | Subgroups included OCD (2) |
| Condition‐specific anxiety symptoms As assessed by Y‐BOCS3 (scale from 0 to 40, better indicated by a lower score) | The mean condition‐specific anxiety symptoms ranged across control groups from 11‐13.8 points | The mean condition‐specific anxiety symptoms in the intervention groups was 0.46 higher (3.63 lower to 4.55 higher) | MD** 0.46 (‐3.63 to 4.55) | 131 participants (4 studies) | ⊕⊝⊝⊝ very low1,4 | Subgroups included: OCD (3) and PTSD (1). For OCD one study found an improvement with placebo compared to DCS, SMD 0.70 (0.17 to 1.24) |
| Co‐morbid symptoms of depression As assessed by CDI5 (scale from 0 to 54, better indicated by a lower score) | The mean co‐morbid symptoms of depression ranged across control groups from 2.2‐16.2 points | The mean co‐morbid symptoms of depression in the intervention groups was 0.62 higher (4.06 lower to 5.38 higher) | MD** 0.62 (‐4.06 to 5.38) | 114 participants (3 studies) | ⊕⊝⊝⊝ very low1,6 | Subgroups included OCD (2) and PTSD (1). For PTSD one study found an improvement with placebo compared to DCS, SMD 0.60 (0.06 to 1.13) |
| Co‐morbid anxiety symptoms As assessed by each study | See comment | 104 participants (3 studies) | ⊕⊝⊝⊝ very low1,7,8 | Heterogeneity was considerable (I2 = 77%), consequently no pooled estimate was calculated. Subgroups included OCD, SMD ‐0.35 (‐0.93 to 0.23, 2 studies, 47 participants) and PTSD, SMD 0.80 (0.26 to 1.34, 1 study, 57 participants) | ||
| Quality of life | No study was found that reported on this outcome. | |||||
| *The basis for the assumed risk is the control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). **Back‐estimated from the SMD, see footnotes for further details. CDI: Child Depression Inventory; CI: Confidence interval; DCS: d‐cycloserine; MASC: Multidimensional Anxiety Scale for Children; OCD: Obsessive compulsive disorder; PD: Panic disorder; PTSD: Post‐traumatic stress disorder; RR: Risk ratio; SAnD: social anxiety disorder; SMD: standardised mean difference; Y‐BOCS: Yale‐Brown Obsessive Compulsive Scale | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 Downgraded 2 steps for imprecision: the total sample size is lower than the calculated optimal information size, and the confidence intervals are wide including both appreciable benefit and no effect. 2 Downgraded 1 for indirectness: withdrawals from treatment is not a direct measure of treatment acceptability. 3 Three of the four studies used the Y‐BOCS. Scores were back‐estimated to the Y‐BOCS from the SMD 0.07 (‐0.55 to 0.69) using the control group SD 6.6 from the representative study Storch 2010. 4 Downgraded 1 step for inconsistency: there was substantial heterogeneity between subgroups (I2 = 66%). 5 Two of the three studies used the CDI. Scores were back‐estimated to the CDI from the SMD 0.08 (‐0.52 to 0.69) using the control group SD 7.8 from the representative study Scheeringa 2014. 6 Downgraded 1 step for inconsistency: there was substantial heterogeneity between subgroups (I2 = 60%). 7 Downgraded 1 step for risk of bias: two of the three included studies did not report details on allocation concealment. 8 Downgraded 1 step for inconsistency: there was considerable heterogeneity between subgroups (I2 = 77%), consequently the subgroups were not pooled.