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. 2023 Oct 9;2023(10):CD011769. doi: 10.1002/14651858.CD011769.pub2

Comparison 3. ADHD‐related medications vs placebo.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
3.1 Irritability 10 400 Std. Mean Difference (IV, Random, 95% CI) ‐0.20 [‐0.40, ‐0.01]
3.1.1 Irritability: non‐stimulant ADHD‐related drugs 8 342 Std. Mean Difference (IV, Random, 95% CI) ‐0.16 [‐0.38, 0.05]
3.1.2 Irritability: stimulant ADHD‐related drugs 2 58 Std. Mean Difference (IV, Random, 95% CI) ‐0.45 [‐0.97, 0.08]
3.2 Self‐injury 1 16 Std. Mean Difference (IV, Random, 95% CI) ‐0.62 [‐1.63, 0.39]
3.3 Adverse effects: cardiovascular 3 114 Risk Ratio (IV, Random, 95% CI) 0.64 [0.16, 2.54]
3.3.1 Bradycardia 1 66 Risk Ratio (IV, Random, 95% CI) 0.36 [0.09, 1.37]
3.3.2 Tachycardia 2 48 Risk Ratio (IV, Random, 95% CI) 3.52 [0.44, 27.85]
3.4 Adverse effects: gastrointestinal 9   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.4.1 Constipation 5 220 Risk Ratio (IV, Random, 95% CI) 2.68 [1.61, 4.45]
3.4.2 Diarrhoea 6 426 Risk Ratio (IV, Random, 95% CI) 0.81 [0.46, 1.40]
3.4.3 Dry mouth 3 102 Risk Ratio (IV, Random, 95% CI) 5.92 [1.86, 18.81]
3.4.4 Nausea 5 239 Risk Ratio (IV, Random, 95% CI) 3.08 [1.51, 6.29]
3.4.5 Stomachache 2 86 Risk Ratio (IV, Random, 95% CI) 2.58 [1.10, 6.06]
3.4.6 Stomach or abdominal discomfort 6 504 Risk Ratio (IV, Random, 95% CI) 2.26 [1.41, 3.63]
3.4.7 Vomiting 4 347 Risk Ratio (IV, Random, 95% CI) 1.35 [0.81, 2.25]
3.5 Adverse effects: immune system 4   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.5.1 Fever 3 183 Risk Ratio (IV, Random, 95% CI) 0.27 [0.06, 1.27]
3.5.2 Influenza 1 97 Risk Ratio (IV, Random, 95% CI) 7.14 [0.38, 134.69]
3.5.3 Myalgia 2 115 Risk Ratio (IV, Random, 95% CI) 4.72 [0.56, 39.55]
3.5.4 Weakness 1 62 Risk Ratio (IV, Random, 95% CI) 3.20 [0.35, 29.10]
3.6 Adverse effects: metabolic (dichotomous) 9   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.6.1 Decreased appetite 9 511 Risk Ratio (IV, Random, 95% CI) 2.15 [1.55, 2.99]
3.6.2 Increased appetite 2 122 Risk Ratio (IV, Random, 95% CI) 0.67 [0.14, 3.34]
3.6.3 Increased energy 1 62 Risk Ratio (IV, Random, 95% CI) 1.60 [0.65, 3.95]
3.7 Adverse effects: neurological (dichotomous) 9   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.7.1 Aggression 5 365 Risk Ratio (IV, Random, 95% CI) 0.95 [0.58, 1.53]
3.7.2 Agitation 1 128 Risk Ratio (IV, Random, 95% CI) 0.95 [0.56, 1.60]
3.7.3 Dizziness 3 175 Risk Ratio (IV, Random, 95% CI) 2.17 [0.63, 7.53]
3.7.4 Drowsiness 4 186 Risk Ratio (IV, Random, 95% CI) 3.42 [1.54, 7.59]
3.7.5 Emotional / tearful 2 128 Risk Ratio (IV, Random, 95% CI) 6.32 [2.47, 16.18]
3.7.6 Fatigue 4 235 Risk Ratio (IV, Random, 95% CI) 3.73 [1.98, 7.03]
3.7.7 Headache 8 383 Risk Ratio (IV, Random, 95% CI) 1.63 [1.09, 2.44]
3.7.8 Hyperactivity 2 115 Risk Ratio (IV, Random, 95% CI) 0.68 [0.06, 7.20]
3.7.9 Increased motor activity 1 66 Risk Ratio (IV, Random, 95% CI) 1.89 [0.48, 7.47]
3.7.10 Insomnia 7 411 Risk Ratio (IV, Random, 95% CI) 1.58 [1.01, 2.47]
3.7.11 Irritability 6 336 Risk Ratio (IV, Random, 95% CI) 1.61 [1.25, 2.07]
3.7.12 Motor tics 3 118 Risk Ratio (IV, Random, 95% CI) 2.33 [0.51, 10.69]
3.7.13 Nightmares 2 122 Risk Ratio (IV, Random, 95% CI) 1.48 [0.38, 5.75]
3.7.14 Repetitive behaviour 2 128 Risk Ratio (IV, Random, 95% CI) 1.59 [0.74, 3.39]
3.7.15 Restless 2 76 Risk Ratio (IV, Random, 95% CI) 1.52 [0.06, 40.44]
3.7.16 Sleep disturbance 2 84 Risk Ratio (IV, Random, 95% CI) 1.12 [0.54, 2.31]
3.7.17 Talking excessively 1 62 Risk Ratio (IV, Random, 95% CI) 0.24 [0.06, 1.01]
3.7.18 Waking 1 62 Risk Ratio (IV, Random, 95% CI) 1.60 [0.29, 8.92]
3.7.19 Tremor 1 16 Risk Ratio (IV, Random, 95% CI) 3.00 [0.14, 64.26]
3.8 Adverse effects: neurological (continuous) 1   Mean Difference (IV, Random, 95% CI) Subtotals only
3.8.1 Drowsiness 1 8 Mean Difference (IV, Random, 95% CI) 4.80 [0.55, 9.05]
3.8.2 Decreased activity 1 8 Mean Difference (IV, Random, 95% CI) 2.00 [‐2.66, 6.66]
3.9 Adverse effects: psychological (dichotomous) 5   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.9.1 Anxiety 5 252 Risk Ratio (IV, Random, 95% CI) 1.39 [0.74, 2.62]
3.9.2 Depression 3 152 Risk Ratio (IV, Random, 95% CI) 2.45 [1.12, 5.36]
3.9.3 Mood change 1 40 Risk Ratio (IV, Random, 95% CI) 13.00 [0.78, 216.39]
3.9.4 Self‐injury 3 188 Risk Ratio (IV, Random, 95% CI) 1.67 [0.78, 3.58]
3.9.5 Silly behaviour 1 62 Risk Ratio (IV, Random, 95% CI) 0.64 [0.17, 2.45]
3.9.6 Social withdrawal 2 126 Risk Ratio (IV, Random, 95% CI) 2.28 [0.39, 13.37]
3.10 Adverse effects: respiratory 2   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.10.1 Cough 2 122 Risk Ratio (IV, Random, 95% CI) 0.81 [0.26, 2.46]
3.11 Adverse effects: skin 3   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.11.1 Rash 3 102 Risk Ratio (IV, Random, 95% CI) 2.21 [0.79, 6.16]
3.11.2 Skin picking 1 62 Risk Ratio (IV, Random, 95% CI) 0.36 [0.04, 3.23]
3.12 Adverse effects: urinary 2   Risk Ratio (IV, Random, 95% CI) Subtotals only
3.12.1 Enuresis 2 122 Risk Ratio (IV, Random, 95% CI) 0.81 [0.19, 3.55]
3.13 Quality of life 1 54 Std. Mean Difference (IV, Random, 95% CI) 0.21 [‐0.33, 0.75]
3.14 Tolerability/acceptability: loss to follow‐up 9 380 Risk Ratio (IV, Random, 95% CI) 0.91 [0.50, 1.69]
3.14.1 ADHD‐related drugs: loss to follow‐up 9 380 Risk Ratio (IV, Random, 95% CI) 0.91 [0.50, 1.69]
3.15 Subgroup analyses: gender ‐ irritability 9 291 Std. Mean Difference (IV, Random, 95% CI) ‐0.25 [‐0.48, ‐0.01]
3.15.1 Male participants only 2 17 Std. Mean Difference (IV, Random, 95% CI) ‐0.52 [‐1.50, 0.47]
3.15.2 Male and female participants 7 274 Std. Mean Difference (IV, Random, 95% CI) ‐0.23 [‐0.47, 0.01]
3.16 Subgroup analyses: age ‐ irritability 9 293 Std. Mean Difference (IV, Random, 95% CI) ‐0.25 [‐0.48, ‐0.02]
3.16.1 Adults and children 1 9 Std. Mean Difference (IV, Random, 95% CI) ‐0.48 [‐1.83, 0.87]
3.16.2 Children only 8 284 Std. Mean Difference (IV, Random, 95% CI) ‐0.25 [‐0.48, ‐0.01]