| 2.1 Irritability |
8 |
466 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.18 [‐0.37, ‐0.00] |
| 2.1.1 Secretin |
3 |
69 |
Std. Mean Difference (IV, Random, 95% CI) |
0.02 [‐0.46, 0.49] |
| 2.1.2 ACTH |
1 |
14 |
Std. Mean Difference (IV, Random, 95% CI) |
0.40 [‐0.66, 1.46] |
| 2.1.3 Oxytocin |
3 |
353 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.24 [‐0.45, ‐0.03] |
| 2.1.4 Vasopressin |
1 |
30 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.29 [‐1.02, 0.43] |
| 2.2 Self‐injury |
1 |
100 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.35 [‐0.74, 0.05] |
| 2.2.1 Endpoint |
1 |
50 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.37 [‐0.93, 0.19] |
| 2.2.2 Three month follow‐up |
1 |
50 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.32 [‐0.88, 0.23] |
| 2.3 Adverse effects: cardiovascular |
3 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 2.3.1 Cardiac disorders |
3 |
456 |
Risk Ratio (M‐H, Random, 95% CI) |
1.45 [0.23, 9.05] |
| 2.3.2 Vascular disorders |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.06, 15.57] |
| 2.3.3 Palpitations |
1 |
290 |
Risk Ratio (M‐H, Random, 95% CI) |
2.96 [0.12, 72.04] |
| 2.4 Adverse effects: gastrointestinal |
6 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.4.1 Abdominal pain or discomfort |
1 |
290 |
Risk Ratio (IV, Random, 95% CI) |
0.42 [0.17, 1.07] |
| 2.4.2 Constipation |
3 |
361 |
Risk Ratio (IV, Random, 95% CI) |
0.89 [0.46, 1.73] |
| 2.4.3 Diarrhoea |
5 |
450 |
Risk Ratio (IV, Random, 95% CI) |
0.71 [0.39, 1.28] |
| 2.4.4 Dry mouth |
2 |
350 |
Risk Ratio (IV, Random, 95% CI) |
0.43 [0.06, 2.88] |
| 2.4.5 Encopresis |
1 |
290 |
Risk Ratio (IV, Random, 95% CI) |
0.74 [0.17, 3.25] |
| 2.4.6 Gastrointestinal disorders |
2 |
166 |
Risk Ratio (IV, Random, 95% CI) |
1.25 [0.35, 4.49] |
| 2.4.7 Nausea |
1 |
60 |
Risk Ratio (IV, Random, 95% CI) |
0.14 [0.01, 2.65] |
| 2.4.8 Salivary hypersecretion |
2 |
319 |
Risk Ratio (IV, Random, 95% CI) |
0.32 [0.03, 2.99] |
| 2.4.9 Stomatitis |
2 |
321 |
Risk Ratio (IV, Random, 95% CI) |
0.13 [0.02, 1.11] |
| 2.4.10 Vomiting |
4 |
409 |
Risk Ratio (IV, Random, 95% CI) |
0.45 [0.21, 0.97] |
| 2.5 Adverse effects: immune system |
1 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 2.5.1 infections and infestations |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
2.00 [0.81, 4.93] |
| 2.6 Adverse effects: metabolic (dichotomous) |
5 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.6.1 Decreased appetite |
4 |
409 |
Risk Ratio (IV, Random, 95% CI) |
0.67 [0.37, 1.22] |
| 2.6.2 Increased appetite |
2 |
350 |
Risk Ratio (IV, Random, 95% CI) |
1.74 [0.96, 3.16] |
| 2.6.3 Metabolism and nutrition disorders |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
0.50 [0.05, 5.35] |
| 2.6.4 Thirst |
2 |
319 |
Risk Ratio (IV, Random, 95% CI) |
1.42 [0.35, 5.67] |
| 2.6.5 Weight gain |
1 |
290 |
Risk Ratio (IV, Random, 95% CI) |
1.21 [0.52, 2.82] |
| 2.6.6 Weight loss |
1 |
290 |
Risk Ratio (IV, Random, 95% CI) |
1.97 [0.69, 5.63] |
| 2.7 Adverse effects: metabolic (continuous) |
1 |
24 |
Mean Difference (IV, Random, 95% CI) |
‐0.45 [‐1.76, 0.86] |
| 2.7.1 Mean change in weight (kg) |
1 |
24 |
Mean Difference (IV, Random, 95% CI) |
‐0.45 [‐1.76, 0.86] |
| 2.8 Adverse effects: musculoskeletal |
3 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.8.1 Muscle spasms |
1 |
29 |
Risk Ratio (IV, Random, 95% CI) |
2.81 [0.12, 63.83] |
| 2.8.2 Musculoskeletal and connective tissue disorders |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
3.00 [0.12, 72.02] |
| 2.8.3 Rhabdomyolysis |
1 |
220 |
Risk Ratio (IV, Random, 95% CI) |
1.47 [0.06, 35.64] |
| 2.9 Adverse effects: neurological |
11 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.9.1 Absence seizures |
1 |
19 |
Risk Ratio (IV, Random, 95% CI) |
2.73 [0.12, 59.57] |
| 2.9.2 Aggression |
3 |
356 |
Risk Ratio (IV, Random, 95% CI) |
0.91 [0.57, 1.44] |
| 2.9.3 Agitation |
3 |
344 |
Risk Ratio (IV, Random, 95% CI) |
1.12 [0.65, 1.94] |
| 2.9.4 Decreased attention |
3 |
108 |
Risk Ratio (IV, Random, 95% CI) |
1.46 [0.24, 8.84] |
| 2.9.5 Dizziness |
3 |
369 |
Risk Ratio (IV, Random, 95% CI) |
0.65 [0.08, 5.27] |
| 2.9.6 Dysphoria |
1 |
290 |
Risk Ratio (IV, Random, 95% CI) |
0.33 [0.01, 8.00] |
| 2.9.7 Excessive talking |
1 |
29 |
Risk Ratio (IV, Random, 95% CI) |
2.81 [0.12, 63.83] |
| 2.9.8 Fatigue |
3 |
120 |
Risk Ratio (IV, Random, 95% CI) |
0.91 [0.50, 1.65] |
| 2.9.9 Forgetfulness |
1 |
19 |
Risk Ratio (IV, Random, 95% CI) |
2.73 [0.12, 59.57] |
| 2.9.10 Headache |
7 |
689 |
Risk Ratio (IV, Random, 95% CI) |
0.58 [0.38, 0.89] |
| 2.9.11 Insomnia |
6 |
477 |
Risk Ratio (IV, Random, 95% CI) |
0.72 [0.50, 1.04] |
| 2.9.12 Irritability |
6 |
655 |
Risk Ratio (IV, Random, 95% CI) |
0.86 [0.68, 1.10] |
| 2.9.13 Leg shaking |
1 |
19 |
Risk Ratio (IV, Random, 95% CI) |
2.73 [0.12, 59.57] |
| 2.9.14 Nervous systems disorders |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
1.67 [0.42, 6.62] |
| 2.9.15 Oppositional |
1 |
25 |
Risk Ratio (IV, Random, 95% CI) |
0.72 [0.14, 3.61] |
| 2.9.16 Restlessness |
2 |
319 |
Risk Ratio (IV, Random, 95% CI) |
1.64 [0.17, 15.47] |
| 2.9.17 Seizure |
1 |
29 |
Risk Ratio (IV, Random, 95% CI) |
2.81 [0.12, 63.83] |
| 2.9.18 Sedation |
2 |
350 |
Risk Ratio (IV, Random, 95% CI) |
1.69 [0.87, 3.27] |
| 2.9.19 Somnolence |
2 |
89 |
Risk Ratio (IV, Random, 95% CI) |
3.81 [0.44, 32.96] |
| 2.9.20 Tics |
2 |
309 |
Risk Ratio (IV, Random, 95% CI) |
0.63 [0.16, 2.38] |
| 2.10 Adverse effects: psychological |
6 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.10.1 Anxiety |
2 |
97 |
Risk Ratio (IV, Random, 95% CI) |
3.05 [0.50, 18.55] |
| 2.10.2 Depression |
4 |
427 |
Risk Ratio (IV, Random, 95% CI) |
0.89 [0.29, 2.68] |
| 2.10.3 Panic attack |
1 |
19 |
Risk Ratio (IV, Random, 95% CI) |
0.30 [0.01, 6.62] |
| 2.10.4 Psychiatric |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
4.00 [0.46, 34.61] |
| 2.10.5 Self‐injury |
2 |
118 |
Risk Ratio (IV, Random, 95% CI) |
1.00 [0.11, 9.35] |
| 2.11 Adverse effects: respiratory |
10 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.11.1 Cold symptoms |
2 |
73 |
Risk Ratio (IV, Random, 95% CI) |
0.65 [0.26, 1.65] |
| 2.11.2 Cough |
5 |
430 |
Risk Ratio (IV, Random, 95% CI) |
1.35 [0.81, 2.25] |
| 2.11.3 Croup |
1 |
25 |
Risk Ratio (IV, Random, 95% CI) |
3.23 [0.14, 72.46] |
| 2.11.4 Epistaxis |
3 |
379 |
Risk Ratio (IV, Random, 95% CI) |
1.21 [0.63, 2.31] |
| 2.11.5 Nasal congestion |
5 |
468 |
Risk Ratio (IV, Random, 95% CI) |
0.79 [0.59, 1.05] |
| 2.11.6 Nasal irritation/runny nose |
1 |
40 |
Risk Ratio (IV, Random, 95% CI) |
0.55 [0.10, 2.92] |
| 2.11.7 Nasopharyngitis |
1 |
29 |
Risk Ratio (IV, Random, 95% CI) |
0.93 [0.15, 5.76] |
| 2.11.8 Respiratory, thoracic and mediastinal disorders |
2 |
147 |
Risk Ratio (IV, Random, 95% CI) |
0.49 [0.09, 2.56] |
| 2.11.9 Sinusitis |
1 |
29 |
Risk Ratio (IV, Random, 95% CI) |
0.47 [0.05, 4.60] |
| 2.11.10 Upper respiratory tract infection |
2 |
273 |
Risk Ratio (IV, Random, 95% CI) |
1.10 [0.35, 3.47] |
| 2.12 Adverse effects: skin |
5 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 2.12.1 General/systemic disorders and administration site conditions |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
4.00 [0.46, 34.61] |
| 2.12.2 Skin rash |
4 |
416 |
Risk Ratio (IV, Random, 95% CI) |
1.12 [0.63, 1.97] |
| 2.12.3 Skin and subcutaneous tissue disorders |
1 |
106 |
Risk Ratio (IV, Random, 95% CI) |
5.00 [0.25, 101.73] |
| 2.13 Adverse effects: urinary |
2 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 2.13.1 Renal and urinary disorders |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
3.00 [0.12, 72.02] |
| 2.13.2 Enuresis |
1 |
290 |
Risk Ratio (M‐H, Random, 95% CI) |
0.18 [0.06, 0.62] |
| 2.14 Adverse effects: other |
3 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 2.14.1 Injury, poisoning, and procedural complications |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
3.00 [0.12, 72.02] |
| 2.14.2 Investigations |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
0.50 [0.05, 5.35] |
| 2.14.3 Lymphadenopathy |
1 |
60 |
Risk Ratio (M‐H, Random, 95% CI) |
0.33 [0.01, 7.87] |
| 2.14.4 Neoplasms: benign, malignant, and unspecified |
1 |
106 |
Risk Ratio (M‐H, Random, 95% CI) |
3.00 [0.12, 72.02] |
| 2.14.5 Troponin I increased |
1 |
220 |
Risk Ratio (M‐H, Random, 95% CI) |
1.47 [0.06, 35.64] |
| 2.15 Quality of life |
4 |
191 |
Std. Mean Difference (IV, Random, 95% CI) |
0.70 [‐0.12, 1.53] |
| 2.15.1 Oxytocin |
2 |
37 |
Std. Mean Difference (IV, Random, 95% CI) |
0.24 [‐0.74, 1.21] |
| 2.15.2 Vasopressin |
1 |
30 |
Std. Mean Difference (IV, Random, 95% CI) |
0.55 [‐0.19, 1.29] |
| 2.15.3 Balovaptan |
1 |
124 |
Std. Mean Difference (IV, Random, 95% CI) |
1.54 [1.14, 1.95] |
| 2.16 Tolerability/acceptability: loss to follow‐up |
14 |
1312 |
Risk Ratio (IV, Random, 95% CI) |
1.10 [0.87, 1.40] |
| 2.17 Subgroup analyses: gender ‐ irritability |
10 |
654 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.12 [‐0.28, 0.03] |
| 2.17.1 Male and female participants |
8 |
563 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.14 [‐0.30, 0.03] |
| 2.17.2 Male participants only |
2 |
91 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.11 [‐0.76, 0.54] |
