Summary of findings 1. Methylphenidate compared with placebo or no intervention for children and adolescents with ADHD.
| Methylphenidate compared with placebo or no intervention for ADHD | ||||||
| Patient or population: children and adolescents (up to and including 18 years of age) with ADHD Settings: outpatient clinic, inpatient hospital ward and summer school Intervention: methylphenidate Comparison: placebo or no intervention | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | Number of participants (trials) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo or no intervention | Methylphenidate | |||||
|
ADHD symptoms: all parallel‐group trials and first‐period cross‐over trials
ADHD Rating Scale (teacher‐rated) Average trial duration: 68.7 days |
Mean ADHD symptom score in the intervention groups corresponds to a mean difference of −10.58 (95% CI −12.58 to −8.72) on ADHD Rating Scale |
SMD −0.74 (−0.88 to −0.61) |
1728 (21 trials) |
⊕⊝⊝⊝ Very lowa,b | The analysis was conducted on a standardised scale with data from studies that used different teacher‐rated scales of symptoms (Conners' Teacher Rating Scale (CTRS), Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) Scale, The Swanson, Nolan and Pelham (SNAP) Scale ‐ Teacher, Fremdbeurteilungsbogen für Hyperkinetische Störungen (FBB‐HKS)). We translated the effect size on to the ADHD Rating Scale from the SMD. | |
| Proportion of participants with one or more serious adverse events | Trial population | RR 0.80 (0.39 to 1.67) | 3673 (26 trials) |
⊕⊝⊝⊝ Verylowa,c | TSA RIS = 9349 TSA showed a RR of 0.91 (TSA‐adjusted Cl 0.31 to 2.68) |
|
| 8 per 1000 | 6 per 1000 (5 less to 5 more) | |||||
| Proportion of participants with one or more adverse events considered non‐serious | Trial population |
RR 1.23 (1.11 to 1.37) |
5342 (35 trials) |
⊕⊝⊝⊝ Verylowa,b | TSA RIS = 9139 TSA showed a RR of 1.22 (TSA‐adjusted Cl 1.08 to 1.43) | |
| 437 per 1000 | 538 per 1000 (348 less to 162 more) | |||||
| General behaviour: all parallel‐group trials and first‐period cross‐over trials General behaviour rating scales (teacher‐rated) | Mean general behaviour score in the intervention groups was 0.62 standard mean deviations lower (95% CI 0.91 lower to 0.33 lower) |
SMD −0.62 (−0.91 to −0.33) |
792 (7 trials) | ⊕⊝⊝⊝ Very lowa,b,d | ||
|
Quality of life (parent‐rated) |
Mean quality‐of‐life score in the intervention groups corresponds to a mean difference of 4.94 (95% CI −0.37 to 10.25) on the Child Health Questionnaire |
SMD 0.40 (−0.03 to 0.83) |
608 (4 trials) | ⊕⊝⊝⊝ Verylowa,b,c,e | ||
| *The basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. 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). ADHD: attention deficit hyperactivity disorder; CI: confidence interval; RIS: required information size; RR: risk ratio; SMD: standardised mean difference; TSA: Trial Sequential Analysis | ||||||
| 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. | ||||||
aDowngraded two levels due to high risk of bias (systematic errors causing overestimation of benefits and underestimation of harms) in several risk of bias domains, including lack of sufficient blinding and selective outcome reporting (many of the included trials did not report on this outcome). bDowngraded one level due to inconsistency: moderate statistical heterogeneity. cDowngraded two levels due to imprecision: wide confidence intervals and/or the accrued number of participants was below 50% of the diversity‐adjusted required information size (DARIS) in Trial Sequential Analysis. dDowngraded one level due to indirectness: children's general behaviour was assessed by different types of rating scales with different focus on behaviour. e Downgraded one level due to indirectness: children's quality of life was assessed by their parents.