Summary of findings 1. D‐cycloserine versus placebo for the treatment of social skills deficits in people with autism spectrum disorder.
| D‐cycloserine versus placebo for the treatment of social skills deficits in people with autism spectrum disorder | ||||||
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Patient or population: children aged 5 to 11 years with ASD Setting: academic autism treatment centres, local schools and community organisations from Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre Intervention: D‐cycloserine 50 mg weekly for 10 weeks plus social skills training Comparison: placebo weekly for 10 weeks plus social skills training | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) |
№ of participants (studies) |
Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with D‐cycloserine | |||||
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Social interaction impairment
Assessed with: Social Responsiveness Scale (SRS)
Scale range: 0 to 195 Follow‐up: 1 week after the end of treatment |
The mean change scores between baseline and 1 week post‐treatment was 17 points lower (better) in the placebo group. | The mean change in SRS score in the D‐cycloserine group was 3.61 points higher (worsening) than in placebo group (5.6 lower to 12.82 higher). | ‐ | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | Positive scores reflect a greater improvement in social communication for participants in the placebo group compared to the intervention group. A negative score would reflect a greater improvement in the intervention group compared with the placebo group. |
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Social communication impairment
Assessed with: ABC parent‐rated scores on the inappropriate speech subscale
Scale from: 0 to 12 Follow‐up: 1 week after the end of treatment |
The mean change from baseline to 1 week post‐treatment was an increase (worsening) of 0.35 points in the control group. | The mean change in ABC scores on inappropriate speech subscale in the D‐cycloserine group was 1.08 points lower (better) than in the placebo group (2.34 lower to 0.18 higher). | ‐ | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | Positive scores reflect a greater improvement in inappropriate speech for participants in the placebo group compared to the intervention group. A negative score would reflect a greater improvement in the intervention group compared with the placebo group. |
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Stereotyped patterns of behaviour and interests
Assessed with: ABC, parent‐rated scores on the stereotypy subscale
Scale from: 0 to 21 Follow‐up: 1 week after the end of treatment |
The mean change from baseline to 1 week post‐treatment was a decline (better) of 0.45 points in the control group. | The mean change in ABC scores on stereotypy subscale in the D‐cycloserine group was 0.12 points higher (worsening) than in the placebo group (1.71 lower to 1.95 higher). | ‐ | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | Positive scores reflect a greater improvement in stereotyped patterns of behaviour and interests for participants in the placebo group compared to the intervention group. A negative score would reflect a greater improvement in the intervention group compared with the placebo group. |
| Total adverse events Assessed with: reports of adverse events | Study population | RR 1.11 (0.94 to 1.31) | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | RR > 1 means increased adverse outcomes in D‐cycloserine group | |
| 879 in 1000 | 975 in 1000 (826 to 1000) | |||||
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Non‐core symptoms of ASD
Assessed with: Clinical Global Impression‐Improvement (CGI‐I) scale Scale from: 1 to 7 (Responders to treatment = CGI‐I score of 1 or 2, or non‐responders to treatment = CGI‐I score of 3 or higher) Follow‐up: 1 week after the end of treatment |
Study population | RR 0.97 (0.49, 1.93) | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | RR < 1 means reduced non‐core symptoms in D‐cycloserine group. | |
| 333 in 1000 | 324 in 1000 (145 to 570) | |||||
| Tolerability Assessed with: number of dropouts | Study population | RR 0.32 (0.01, 7.68) | 67 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | RR < 1 means reduced number of dropouts in D‐cycloserine group. | |
| 30 in 1000 | 10 in 1000 (0 to 200) | |||||
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Rate ratio; OR: Odds ratio | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect | ||||||
aWe downgraded by one level due to risk of bias: we rated the potential of selection bias as unclear due to the method of randomisation and allocation being unclear in the report. bWe downgraded the evidence by one level due to imprecision: small sample size.