Summary of findings 3. Attention deficit hyperactivity disorder (ADHD)‐related drugs compared to placebo for irritability, aggression, and self‐injury in autism spectrum disorder (ASD).
| ADHD‐related medications compared to placebo for irritability, aggression, and self‐injury in autism spectrum disorder (ASD) | ||||||
| Patient or population: participants (any age) with a clinical diagnosis of ASD who have displayed one or more unwanted or challenging behaviours at baseline assessment Setting: hospital inpatient or outpatient centres, education or disability settings, mental health settings, or clinics and research centres associated with universities Intervention: ADHD‐related medications Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with ADHD‐related drugs | |||||
|
Irritability All ADHD‐related medications Follow‐up: short term (up to six months) Measured via Aberrant Behaviour Checklist (Irritability subscale) (Score range (0‐45)) (Aman 1985) and the Ritvo‐Freeman Real Life Rating Scale (Freeman 1986 (score range 0‐15). Lower scores indicate lower severity. |
See comment | SMD 0.20 lower (95% CI 0.40 lower to 0.01 lower) | ‐ | 400 (10 studies: methylphenidate 2 studies; clonidine 2 studies; guanfacine 2 studies; atomoxetine 4 studies) | ⊕⊕⊝⊝ Lowa |
An SMD of 0.20 may represent a small effect size (small = 0.2; medium =0.5; large = 0.8, Cohen 1988). |
| Aggression | No data were reported for this outcome in this comparison | |||||
|
Self‐injury Follow‐up: short term (up to six months) Measured via the Repetitive Behaviour Scale ‐ Revised (self‐injury subscale) (Bodfish 2000) |
See comment | SMD 0.62 lower (95% CI 1.63 lower to 0.39 higher) | ‐ | 16 participants (1 study) | ⊕⊝⊝⊝ Very lowb |
There was no clear evidence of a difference, but results are uncertain. |
|
Adverse effects Follow‐up: short term (up to six months) |
Neurological | There was evidence of a higher rate of AEs in the intervention group for drowsiness | RR 3.42 (95% CI 1.54 higher to 7.59 higher); atomoxetine 2 studies; guanfacine 1 study; methylphenidate 1 study) | 511 (9 studies) |
⊕⊝⊝⊝ Very lowc |
‐ |
| There was evidence of a higher rate of AEs in the intervention group for emotional | RR 6.32 (95% CI 2.47 higher to 16.18 higher); methylphenidate 1 study; guanfacine 1 study | |||||
| There was evidence of a higher rate of AEs in the intervention group for fatigue | RR 3.73 (95% CI 1.98 higher to 7.03higher); atomoxetine 3 studies; guanfacine 1 study | |||||
| There was evidence of a higher rate of AEs in the intervention group for headache | RR 1.63 (95% CI 1.09 higher to 2.44 higher); atomoxetine 4 studies; methylphenidate 2 studies; guanfacine 1 study; amphetamine 1 study | |||||
| There was evidence of a higher rate of AEs in the intervention group for insomnia | RR 1.58 (95% CI 1.01 higher to 2.47 higher); methylphenidate 2 studies; atomoxetine 3 studies; guanfacine 1 study; amphetamine 1 study | |||||
| There was evidence of a higher rate of AEs in the intervention group for irritability | RR 1.61 (95% CI 1.25 to 2.07 higher); atomoxetine 3 studies; guanfacine 1 study; methylphenidate 2 studies | |||||
| There was little to no evidence of a difference between groups for aggression (P = 0.82), agitation (P = 0.85), dizziness (P = 0.22), drowsiness (P = 0.003), hyperactivity (P = 0.75), increased motor activity (P = 0.36), motor tics (P = 0.28), nightmares (P = 0.57), repetitive behaviour (P = 0.23), restlessness (P = 0.80), sleep disturbance (P = 0.76), talking excessively (P = 0.05), waking (P = 0.59), or tremor (P = 0.48). | ||||||
| Psychological | There was evidence of a higher rate of depression in the intervention group | RR 2.45 higher (95% CI 1.12 higher to 5.36 higher); methylphenidate 2 studies; guanfacine 1 study | 252 (5 studies) |
⊕⊝⊝⊝ Very lowd |
‐ | |
| There was little to no evidence of a difference between groups for anxiety (P = 0.30); mood change (P = 0.07), "silly behaviour" (P = 0.51), self‐injury (P = 0.19), or social withdrawal (P = 0.36). | ||||||
| Metabolic | There was evidence of a higher rate of AEs in the intervention group for decreased appetite | RR 2.15 (95% CI 1.55 higher to 2.99 higher); atomoxetine 5 studies; guanfacine 1 study; amphetamine 1 study; methylphenidate 2 studies | 511 (9 studies) |
⊕⊝⊝⊝ Very lowc |
‐ | |
| There was little to no evidence of a difference between groups for increased appetite (P = 0.63) and increased energy (P = 0.31). | ||||||
| Musculoskeletal | No data were reported for this outcome in this comparison. | |||||
| AE: adverse effect; ASD: autism spectrum disorder; CI: confidence interval; RR: risk ratio; SMD: standardised mean difference | ||||||
| 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 1 level due to study limitations (high risk of bias across multiple domains) and 1 level due to imprecision (95% confidence intervals includes both benefit and harm). bDowngraded 1 level due to study limitations (high risk of bias across multiple domains) and 1 level for indirectness (available evidence relates to children only) and 1 level for imprecision (small sample size of n = 16 and 95% confidence intervals includes both benefit and harm). cDowngraded 1 level due to study limitations (only involving children), 1 level due to inconsistency (direction of effect varies across studies) and 1 level due to imprecision (95% confidence intervals includes both benefit and harm). dDowngraded 1 level due to study limitations (high risk of bias across multiple domains), 1 level due to inconsistency (direction of effect varies across studies) and 1 level due to imprecision (95% confidence intervals includes both benefit and harm).