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

Comparison 14. Experimental versus placebo.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
14.1 Irritability 28 1205 Std. Mean Difference (IV, Random, 95% CI) ‐0.30 [‐0.53, ‐0.07]
14.1.1 Arbaclofen 1 130 Std. Mean Difference (IV, Random, 95% CI) ‐0.33 [‐0.68, 0.02]
14.1.2 Baclofen 1 58 Std. Mean Difference (IV, Random, 95% CI) 0.88 [0.34, 1.42]
14.1.3 Bumetanide 2 104 Std. Mean Difference (IV, Random, 95% CI) ‐0.74 [‐1.84, 0.37]
14.1.4 Celecoxib 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐1.27 [‐1.95, ‐0.58]
14.1.5 Dextromethorphan 1 8 Std. Mean Difference (IV, Random, 95% CI) ‐0.13 [‐1.52, 1.26]
14.1.6 Dextromethorphan/quinidine 1 14 Std. Mean Difference (IV, Random, 95% CI) ‐0.37 [‐1.43, 0.69]
14.1.7 Folinic acid 1 55 Std. Mean Difference (IV, Random, 95% CI) 0.63 [0.08, 1.17]
14.1.8 Lofexedine 1 12 Std. Mean Difference (IV, Random, 95% CI) ‐0.50 [‐1.66, 0.66]
14.1.9 L‐carnosine 1 42 Std. Mean Difference (IV, Random, 95% CI) 0.20 [‐0.41, 0.80]
14.1.10 Minocycline 1 46 Std. Mean Difference (IV, Random, 95% CI) 0.89 [0.28, 1.50]
14.1.11 N‐acetylcysteine 4 125 Std. Mean Difference (IV, Random, 95% CI) ‐0.61 [‐1.16, ‐0.06]
14.1.12 Naltrexone 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐0.18 [‐0.80, 0.44]
14.1.13 Nicotine 1 8 Std. Mean Difference (IV, Random, 95% CI) ‐0.72 [‐2.19, 0.75]
14.1.14 Pioglitazone 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐0.77 [‐1.42, ‐0.13]
14.1.15 Palmitoylethanolamide 1 62 Std. Mean Difference (IV, Random, 95% CI) ‐0.49 [‐1.00, 0.01]
14.1.16 Prednisolone (steroid) 1 26 Std. Mean Difference (IV, Random, 95% CI) ‐0.19 [‐0.96, 0.58]
14.1.17 Pregnenolone 1 59 Std. Mean Difference (IV, Random, 95% CI) ‐0.55 [‐1.07, ‐0.03]
14.1.18 Propentofylline 1 48 Std. Mean Difference (IV, Random, 95% CI) 0.56 [‐0.01, 1.14]
14.1.19 Resveratol 1 62 Std. Mean Difference (IV, Random, 95% CI) ‐0.29 [‐0.79, 0.21]
14.1.20 Riluzole 2 54 Std. Mean Difference (IV, Random, 95% CI) ‐0.34 [‐1.10, 0.42]
14.1.21 Simvastatin 1 66 Std. Mean Difference (IV, Random, 95% CI) ‐0.88 [‐1.38, ‐0.37]
14.1.22 Sulforaphane 1 60 Std. Mean Difference (IV, Random, 95% CI) ‐0.86 [‐1.39, ‐0.33]
14.1.23 Tetrahydrobiopterin 1 46 Std. Mean Difference (IV, Random, 95% CI) ‐0.10 [‐0.68, 0.48]
14.2 Self‐injury 5 285 Std. Mean Difference (IV, Random, 95% CI) 0.14 [‐0.09, 0.38]
14.2.1 Bumetanide 2 148 Std. Mean Difference (IV, Random, 95% CI) 0.20 [‐0.21, 0.60]
14.2.2 N‐acetylcysteine 2 127 Std. Mean Difference (IV, Random, 95% CI) 0.08 [‐0.29, 0.44]
14.2.3 Trichuris suris ova 1 10 Std. Mean Difference (IV, Random, 95% CI) ‐0.30 [‐1.55, 0.95]
14.3 Adverse effects: gastrointestinal 32   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.3.1 Abdominal pain 14 734 Risk Ratio (IV, Random, 95% CI) 1.38 [0.95, 2.01]
14.3.2 Change in bowel habits 2 54 Risk Ratio (IV, Random, 95% CI) 0.39 [0.05, 3.26]
14.3.3 Constipation 13 665 Risk Ratio (IV, Random, 95% CI) 1.29 [0.77, 2.16]
14.3.4 Diarrhoea 18 982 Risk Ratio (IV, Random, 95% CI) 0.83 [0.55, 1.25]
14.3.5 Drooling 1 11 Risk Ratio (IV, Random, 95% CI) 0.29 [0.01, 5.79]
14.3.6 Dry mouth 5 173 Risk Ratio (IV, Random, 95% CI) 0.87 [0.37, 2.09]
14.3.7 Dyspepsia 1 31 Risk Ratio (IV, Random, 95% CI) 0.31 [0.01, 7.15]
14.3.8 Encopresis 1 31 Risk Ratio (IV, Random, 95% CI) 0.31 [0.01, 7.15]
14.3.9 Flatulance 1 10 Risk Ratio (IV, Random, 95% CI) 3.00 [0.15, 59.89]
14.3.10 Increased salivation 1 40 Risk Ratio (IV, Random, 95% CI) 1.00 [0.39, 2.58]
14.3.11 Nausea 15 768 Risk Ratio (IV, Random, 95% CI) 1.36 [0.90, 2.06]
14.3.12 Thirst 4 224 Risk Ratio (IV, Random, 95% CI) 3.32 [1.10, 10.01]
14.3.13 Vomiting 13 793 Risk Ratio (IV, Random, 95% CI) 1.34 [0.91, 1.98]
14.4 Adverse effects: immune system 2   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.4.1 Fever 2 102 Risk Ratio (IV, Random, 95% CI) 2.94 [0.46, 18.53]
14.4.2 Influenza 1 31 Risk Ratio (IV, Random, 95% CI) 0.31 [0.01, 7.15]
14.5 Adverse effects: metabolic (dichotomous) 27   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.5.1 Decreased appetite 15 806 Risk Ratio (IV, Random, 95% CI) 1.62 [0.95, 2.75]
14.5.2 Hypoglycemia 2 120 Risk Ratio (IV, Random, 95% CI) 0.71 [0.09, 5.68]
14.5.3 Hypokalemia 4 331 Risk Ratio (IV, Random, 95% CI) 12.48 [4.04, 38.62]
14.5.4 Hyponatremia 1 38 Risk Ratio (IV, Random, 95% CI) 3.00 [0.13, 69.31]
14.5.5 Increased appetite 14 676 Risk Ratio (IV, Random, 95% CI) 1.42 [1.02, 1.98]
14.5.6 Weight gain 2 39 Risk Ratio (IV, Random, 95% CI) 0.32 [0.04, 2.77]
14.5.7 Weight loss 4 306 Risk Ratio (IV, Random, 95% CI) 1.49 [0.50, 4.39]
14.5.8 Weight loss (0.12‐0.67 kg) 1 11 Risk Ratio (IV, Random, 95% CI) 9.43 [0.65, 137.77]
14.5.9 Weight loss (0.45‐2.19 kg) 1 11 Risk Ratio (IV, Random, 95% CI) 0.17 [0.01, 2.92]
14.6 Adverse effects: metabolic (continuous) 1 23 Mean Difference (IV, Random, 95% CI) 0.13 [‐0.24, 0.50]
14.6.1 Change in weight (kg) 1 23 Mean Difference (IV, Random, 95% CI) 0.13 [‐0.24, 0.50]
14.7 Adverse effects: musculoskeletal 8   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.7.1 Arthralgia 1 10 Risk Ratio (IV, Random, 95% CI) 0.33 [0.02, 6.65]
14.7.2 Difficulty walking 1 40 Risk Ratio (IV, Random, 95% CI) 0.20 [0.01, 3.92]
14.7.3 Impaired balance 1 12 Risk Ratio (IV, Random, 95% CI) 1.67 [0.08, 33.75]
14.7.4 Myalgia 2 155 Risk Ratio (IV, Random, 95% CI) 1.54 [0.79, 3.04]
14.7.5 Slow movement 1 31 Risk Ratio (IV, Random, 95% CI) 4.17 [0.22, 80.25]
14.7.6 Stiffness 2 43 Risk Ratio (IV, Random, 95% CI) 2.03 [0.41, 10.15]
14.7.7 Weakness 3 90 Risk Ratio (IV, Random, 95% CI) 0.63 [0.21, 1.89]
14.8 Adverse effects: neurological 33   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.8.1 Agitation/excitement 5 220 Risk Ratio (IV, Random, 95% CI) 0.76 [0.39, 1.48]
14.8.2 Anxiety 3 250 Risk Ratio (IV, Random, 95% CI) 1.06 [0.44, 2.57]
14.8.3 Daytime drowsiness 6 172 Risk Ratio (IV, Random, 95% CI) 1.57 [0.75, 3.28]
14.8.4 Dazed 1 11 Risk Ratio (IV, Random, 95% CI) 2.57 [0.13, 52.12]
14.8.5 Difficulty concentrating 1 12 Risk Ratio (IV, Random, 95% CI) 2.50 [0.42, 14.83]
14.8.6 Difficulty sleeping 6 326 Risk Ratio (IV, Random, 95% CI) 0.81 [0.44, 1.50]
14.8.7 Dizziness 9 441 Risk Ratio (IV, Random, 95% CI) 1.21 [0.67, 2.18]
14.8.8 Drowsiness 5 298 Risk Ratio (IV, Random, 95% CI) 3.45 [1.21, 9.81]
14.8.9 Fatigue 7 338 Risk Ratio (IV, Random, 95% CI) 1.23 [0.70, 2.17]
14.8.10 Headache 18 943 Risk Ratio (IV, Random, 95% CI) 0.91 [0.66, 1.26]
14.8.11 Hypoactivity 3 28 Risk Ratio (IV, Random, 95% CI) 0.44 [0.07, 2.95]
14.8.12 Increased aggression 4 149 Risk Ratio (IV, Random, 95% CI) 0.78 [0.36, 1.70]
14.8.13 Increased hyperactivity 6 321 Risk Ratio (IV, Random, 95% CI) 0.75 [0.35, 1.58]
14.8.14 Increased irritability 5 177 Risk Ratio (IV, Random, 95% CI) 1.11 [0.71, 1.72]
14.8.15 Increased stereotypies 1 41 Risk Ratio (IV, Random, 95% CI) 0.52 [0.10, 2.80]
14.8.16 Insomnia 8 488 Risk Ratio (IV, Random, 95% CI) 1.04 [0.66, 1.65]
14.8.17 Migraine 1 10 Risk Ratio (IV, Random, 95% CI) 3.00 [0.15, 59.89]
14.8.18 Nervousness 4 159 Risk Ratio (IV, Random, 95% CI) 1.86 [0.47, 7.37]
14.8.19 New onset seizures 1 46 Risk Ratio (IV, Random, 95% CI) 0.33 [0.01, 7.78]
14.8.20 Restlessness 5 158 Risk Ratio (IV, Random, 95% CI) 1.22 [0.53, 2.82]
14.8.21 Rocking 1 11 Risk Ratio (IV, Random, 95% CI) 0.29 [0.01, 5.79]
14.8.22 Sedation 13 624 Risk Ratio (IV, Random, 95% CI) 0.93 [0.61, 1.42]
14.8.23 Syncope 1 89 Risk Ratio (IV, Random, 95% CI) 2.80 [0.30, 25.94]
14.8.24 Tremor 4 140 Risk Ratio (IV, Random, 95% CI) 1.80 [0.44, 7.37]
14.8.25 Twitching 2 71 Risk Ratio (IV, Random, 95% CI) 3.60 [0.42, 31.04]
14.9 Adverse effects: psychological 10   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.9.1 Anorexia 1 20 Risk Ratio (IV, Random, 95% CI) 0.53 [0.20, 1.40]
14.9.2 Aggression 1 150 Risk Ratio (IV, Random, 95% CI) 1.17 [0.37, 3.66]
14.9.3 Depression 3 108 Risk Ratio (IV, Random, 95% CI) 1.93 [0.62, 6.00]
14.9.4 Increased self‐injurious behaviour 3 105 Risk Ratio (IV, Random, 95% CI) 0.46 [0.11, 1.84]
14.9.5 Irritability 2 162 Risk Ratio (IV, Random, 95% CI) 0.91 [0.36, 2.27]
14.9.6 Mental symptoms 1 20 Risk Ratio (IV, Random, 95% CI) 1.00 [0.41, 2.45]
14.9.7 Repetitive behaviour 1 46 Risk Ratio (IV, Random, 95% CI) 0.50 [0.05, 5.14]
14.9.8 Worsening of temper tantrums 2 52 Risk Ratio (IV, Random, 95% CI) 1.88 [0.30, 11.83]
14.10 Adverse effects: respiratory 6   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.10.1 Aggravation of asthma 1 71 Risk Ratio (IV, Random, 95% CI) 3.26 [0.14, 77.35]
14.10.2 Congestion/cold 4 256 Risk Ratio (IV, Random, 95% CI) 1.02 [0.62, 1.68]
14.10.3 Cough 3 248 Risk Ratio (IV, Random, 95% CI) 1.16 [0.55, 2.49]
14.10.4 Ear infection 1 31 Risk Ratio (IV, Random, 95% CI) 1.88 [0.19, 18.60]
14.10.5 Lung congestion 1 20 Risk Ratio (IV, Random, 95% CI) 1.00 [0.60, 1.68]
14.10.6 Nasopharyngitis 1 150 Risk Ratio (IV, Random, 95% CI) 0.78 [0.22, 2.79]
14.10.7 Respiratory adverse effects 1 71 Risk Ratio (IV, Random, 95% CI) 5.43 [0.27, 109.19]
14.11 Adverse effects: skin 12   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.11.1 Hives 1 31 Risk Ratio (IV, Random, 95% CI) 0.31 [0.01, 7.15]
14.11.2 Itches 2 62 Risk Ratio (IV, Random, 95% CI) 0.55 [0.07, 4.19]
14.11.3 Rash 7 440 Risk Ratio (IV, Random, 95% CI) 0.76 [0.30, 1.92]
14.11.4 Skin adverse effects 1 71 Risk Ratio (IV, Random, 95% CI) 1.09 [0.16, 7.30]
14.11.5 Skin lesion 2 98 Risk Ratio (IV, Random, 95% CI) 1.66 [0.74, 3.70]
14.12 Adverse effects: urinary 5   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.12.1 Diuresis 1 89 Risk Ratio (IV, Random, 95% CI) 0.93 [0.25, 3.51]
14.12.2 Enuresis 3 205 Risk Ratio (IV, Random, 95% CI) 2.70 [0.82, 8.87]
14.12.3 Urinary retention 2 88 Risk Ratio (IV, Random, 95% CI) 0.74 [0.05, 10.49]
14.12.4 Urinary tract infection 1 31 Risk Ratio (IV, Random, 95% CI) 0.31 [0.01, 7.15]
14.13 Adverse effects: other 7   Risk Ratio (IV, Random, 95% CI) Subtotals only
14.13.1 Blurred vision 1 31 Risk Ratio (IV, Random, 95% CI) 2.50 [0.11, 56.98]
14.13.2 Dilated pupils 1 20 Risk Ratio (IV, Random, 95% CI) 0.67 [0.05, 9.19]
14.13.3 Fever 1 150 Risk Ratio (IV, Random, 95% CI) 0.49 [0.13, 1.88]
14.13.4 Sweating 3 129 Risk Ratio (IV, Random, 95% CI) 0.75 [0.15, 3.86]
14.13.5 Vision: conjunctivitis 1 10 Risk Ratio (IV, Random, 95% CI) 0.33 [0.02, 6.65]
14.14 Tolerability/acceptability: loss to follow‐up 30 1913 Risk Ratio (IV, Random, 95% CI) 1.07 [0.89, 1.28]
14.15 Subgroup analyses: age ‐ irritability (option 1) 28 1242 Std. Mean Difference (IV, Random, 95% CI) ‐0.21 [‐0.42, ‐0.00]
14.15.1 Children only 23 1014 Std. Mean Difference (IV, Random, 95% CI) ‐0.21 [‐0.46, 0.04]
14.15.2 Adults only 3 84 Std. Mean Difference (IV, Random, 95% CI) ‐0.26 [‐0.69, 0.17]
14.15.3 Children and adults 2 144 Std. Mean Difference (IV, Random, 95% CI) ‐0.28 [‐0.61, 0.05]
14.16 Subgroup analyses: age ‐ irritability (option 2) 28 1179 Std. Mean Difference (IV, Random, 95% CI) ‐0.20 [‐0.42, 0.01]
14.16.1 Celecoxib: children only 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐1.27 [‐1.95, ‐0.58]
14.16.2 D‐cycloserine: children only 1 67 Std. Mean Difference (IV, Random, 95% CI) ‐0.05 [‐0.53, 0.43]
14.16.3 Dextromethorphan: children only 1 8 Std. Mean Difference (IV, Random, 95% CI) ‐0.13 [‐1.52, 1.26]
14.16.4 Mecamylamine: children only 1 20 Std. Mean Difference (IV, Random, 95% CI) 0.18 [‐0.71, 1.08]
14.16.5 Riluzole: children only 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐0.63 [‐1.27, 0.00]
14.16.6 Riluzole: children and adults 1 14 Std. Mean Difference (IV, Random, 95% CI) 0.18 [‐0.87, 1.23]
14.16.7 Pioglitazone: children only 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐0.77 [‐1.42, ‐0.13]
14.16.8 N‐acetylcysteine: children only 4 125 Std. Mean Difference (IV, Random, 95% CI) ‐0.61 [‐1.16, ‐0.06]
14.16.9 Trichuris suis ova: adults only 1 10 Std. Mean Difference (IV, Random, 95% CI) ‐0.25 [‐1.50, 1.00]
14.16.10 Tetrahydrobiopterin: children only 1 46 Std. Mean Difference (IV, Random, 95% CI) ‐0.10 [‐0.68, 0.48]
14.16.11 Lofexedine: children only 1 12 Std. Mean Difference (IV, Random, 95% CI) ‐0.50 [‐1.66, 0.66]
14.16.12 Naltrexone: adults only 1 20 Std. Mean Difference (IV, Random, 95% CI) ‐0.18 [‐1.05, 0.70]
14.16.13 Minocycline: children only 1 46 Std. Mean Difference (IV, Random, 95% CI) 0.89 [0.28, 1.50]
14.16.14 Propentofylline: children only 1 48 Std. Mean Difference (IV, Random, 95% CI) 0.56 [‐0.01, 1.14]
14.16.15 Sulforaphane: children only 1 60 Std. Mean Difference (IV, Random, 95% CI) ‐0.86 [‐1.39, ‐0.33]
14.16.16 Folinic acid: children only 1 55 Std. Mean Difference (IV, Random, 95% CI) 0.63 [0.08, 1.17]
14.16.17 L‐carnosine: children only 1 42 Std. Mean Difference (IV, Random, 95% CI) 0.20 [‐0.41, 0.80]
14.16.18 Prednisolone (steroid): children only 1 26 Std. Mean Difference (IV, Random, 95% CI) ‐0.19 [‐0.96, 0.58]
14.16.19 Dextromethorphan/quinidine: adults only 1 14 Std. Mean Difference (IV, Random, 95% CI) ‐0.37 [‐1.43, 0.69]
14.16.20 Pregnenolone: children only 1 59 Std. Mean Difference (IV, Random, 95% CI) ‐0.55 [‐1.07, ‐0.03]
14.16.21 Baclofen: children only 1 58 Std. Mean Difference (IV, Random, 95% CI) 0.88 [0.34, 1.42]
14.16.22 Palmitoylethanolamide: children only 1 62 Std. Mean Difference (IV, Random, 95% CI) ‐0.49 [‐1.00, 0.01]
14.16.23 Bumetanide: children only 1 75 Std. Mean Difference (IV, Random, 95% CI) ‐0.10 [‐0.55, 0.35]
14.16.24 Resveratol: children only 1 62 Std. Mean Difference (IV, Random, 95% CI) ‐0.29 [‐0.79, 0.21]
14.16.25 Arbaclofen: children and adults 1 130 Std. Mean Difference (IV, Random, 95% CI) ‐0.33 [‐0.68, 0.02]
14.17 Subgroup analyses: age ‐ self‐injury (option 1) 3 147 Std. Mean Difference (IV, Random, 95% CI) 0.03 [‐0.30, 0.35]
14.17.1 Children only 2 127 Std. Mean Difference (IV, Random, 95% CI) 0.08 [‐0.29, 0.44]
14.17.2 Adults only 1 20 Std. Mean Difference (IV, Random, 95% CI) ‐0.31 [‐1.20, 0.57]
14.18 Subgroup analyses: age ‐ self‐injury (option 2) 5 285 Std. Mean Difference (IV, Random, 95% CI) 0.14 [‐0.09, 0.38]
14.18.1 N‐acetylcysteine: children only 1 98 Std. Mean Difference (IV, Random, 95% CI) 0.18 [‐0.22, 0.58]
14.18.2 N‐acetylcysteine: children only 1 29 Std. Mean Difference (IV, Random, 95% CI) ‐0.26 [‐0.99, 0.48]
14.18.3 Trichuris suis ova: adults only 1 10 Std. Mean Difference (IV, Random, 95% CI) ‐0.30 [‐1.55, 0.95]
14.18.4 Bumetanide: children only 2 148 Std. Mean Difference (IV, Random, 95% CI) 0.20 [‐0.21, 0.60]