| 8.1 Proportion of participants with non‐serious events |
24 |
2696 |
Risk Ratio (IV, Random, 95% CI) |
1.39 [1.13, 1.70] |
| 8.2 Subgroup analysis: total number of non‐serious adverse events according to dose |
24 |
3483 |
Risk Ratio (IV, Random, 95% CI) |
1.31 [1.12, 1.53] |
| 8.2.1 Low dose |
16 |
1539 |
Risk Ratio (IV, Random, 95% CI) |
1.11 [0.94, 1.31] |
| 8.2.2 High dose |
12 |
1080 |
Risk Ratio (IV, Random, 95% CI) |
1.57 [1.22, 2.01] |
| 8.2.3 Unknown dose |
5 |
864 |
Risk Ratio (IV, Random, 95% CI) |
1.50 [0.88, 2.56] |
| 8.3 Nervous system (including psychiatry) |
52 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 8.3.1 Aggression |
3 |
743 |
Risk Ratio (IV, Random, 95% CI) |
0.52 [0.17, 1.60] |
| 8.3.2 Agitation |
2 |
273 |
Risk Ratio (IV, Random, 95% CI) |
1.93 [0.37, 10.16] |
| 8.3.3 Anger |
3 |
264 |
Risk Ratio (IV, Random, 95% CI) |
0.45 [0.26, 0.77] |
| 8.3.4 Behavioural complaints |
1 |
82 |
Risk Ratio (IV, Random, 95% CI) |
0.55 [0.35, 0.86] |
| 8.3.5 Buccal or lingual movements |
5 |
569 |
Risk Ratio (IV, Random, 95% CI) |
1.12 [0.81, 1.55] |
| 8.3.6 Compulsive acts |
1 |
90 |
Risk Ratio (IV, Random, 95% CI) |
2.57 [1.45, 4.56] |
| 8.3.7 Daydreaming |
3 |
222 |
Risk Ratio (IV, Random, 95% CI) |
0.66 [0.44, 0.98] |
| 8.3.8 Dizziness |
12 |
2163 |
Risk Ratio (IV, Random, 95% CI) |
1.06 [0.91, 1.23] |
| 8.3.9 Drowsiness: dull, tired, listless or sleepy |
24 |
3011 |
Risk Ratio (IV, Random, 95% CI) |
0.98 [0.80, 1.20] |
| 8.3.10 Euphoria |
7 |
1457 |
Risk Ratio (IV, Random, 95% CI) |
0.97 [0.72, 1.31] |
| 8.3.11 Headache |
43 |
5981 |
Risk Ratio (IV, Random, 95% CI) |
1.25 [1.06, 1.48] |
| 8.3.12 Thirst |
1 |
211 |
Risk Ratio (IV, Random, 95% CI) |
2.78 [0.11, 69.04] |
| 8.3.13 Irritability |
27 |
4110 |
Risk Ratio (IV, Random, 95% CI) |
0.97 [0.74, 1.27] |
| 8.3.14 Nightmares |
11 |
1738 |
Risk Ratio (IV, Random, 95% CI) |
1.00 [0.73, 1.35] |
| 8.3.15 Overly meticulous |
1 |
96 |
Risk Ratio (IV, Random, 95% CI) |
40.77 [2.35, 706.72] |
| 8.3.16 Obsessive thinking |
1 |
90 |
Risk Ratio (IV, Random, 95% CI) |
2.35 [1.53, 3.62] |
| 8.3.17 Picking at skin or fingers, nail biting, lip or cheek chewing |
18 |
2549 |
Risk Ratio (IV, Random, 95% CI) |
1.04 [0.86, 1.25] |
| 8.3.18 Repetitive language |
1 |
48 |
Risk Ratio (IV, Random, 95% CI) |
1.00 [0.32, 3.10] |
| 8.3.19 Sad, tearful or depressed |
26 |
3510 |
Risk Ratio (IV, Random, 95% CI) |
1.15 [0.96, 1.37] |
| 8.3.20 Socially withdrawn ‐ decreased interaction with others |
15 |
2432 |
Risk Ratio (IV, Random, 95% CI) |
1.36 [0.95, 1.95] |
| 8.3.21 Stares a lot |
11 |
2110 |
Risk Ratio (IV, Random, 95% CI) |
1.04 [0.83, 1.31] |
| 8.3.22 Tics or nervous movements |
24 |
3429 |
Risk Ratio (IV, Random, 95% CI) |
1.23 [1.02, 1.50] |
| 8.3.23 Unusual blinking |
1 |
48 |
Risk Ratio (IV, Random, 95% CI) |
3.13 [0.12, 80.68] |
| 8.3.24 Worried or anxious |
23 |
3366 |
Risk Ratio (IV, Random, 95% CI) |
0.85 [0.66, 1.11] |
| 8.3.25 Fatique |
1 |
211 |
Risk Ratio (IV, Random, 95% CI) |
4.59 [0.22, 94.57] |
| 8.3.26 Emotional lability |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
9.25 [2.24, 38.22] |
| 8.3.27 Dysphoria |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
4.63 [0.23, 94.88] |
| 8.3.28 Moody |
1 |
211 |
Risk Ratio (IV, Random, 95% CI) |
4.59 [0.22, 94.57] |
| 8.3.29 Uninterested |
1 |
1052 |
Risk Ratio (IV, Random, 95% CI) |
1.20 [0.82, 1.75] |
| 8.3.30 Prone to crying |
1 |
1052 |
Risk Ratio (IV, Random, 95% CI) |
1.72 [1.04, 2.86] |
| 8.4 Nervous system (including psychiatry) continuous outcomes |
1 |
40 |
Mean Difference (IV, Fixed, 95% CI) |
‐0.80 [‐3.56, 1.96] |
| 8.4.1 Anxiety |
1 |
40 |
Mean Difference (IV, Fixed, 95% CI) |
‐0.80 [‐3.56, 1.96] |
| 8.5 Digestive system |
48 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 8.5.1 Decreased appetite or loss of appetite |
41 |
6091 |
Risk Ratio (IV, Random, 95% CI) |
3.89 [2.76, 5.48] |
| 8.5.2 Diarrhoea |
5 |
767 |
Risk Ratio (IV, Random, 95% CI) |
0.95 [0.38, 2.34] |
| 8.5.3 Dry mouth |
6 |
496 |
Risk Ratio (IV, Random, 95% CI) |
1.32 [0.59, 2.97] |
| 8.5.4 Dyspepsia |
1 |
62 |
Risk Ratio (IV, Random, 95% CI) |
0.22 [0.02, 2.14] |
| 8.5.5 Nausea |
11 |
1182 |
Risk Ratio (IV, Random, 95% CI) |
1.67 [1.13, 2.46] |
| 8.5.6 Increased appetite |
1 |
136 |
Risk Ratio (IV, Random, 95% CI) |
0.20 [0.08, 0.50] |
| 8.5.7 Stomach ache (abdominal pain) |
38 |
5803 |
Risk Ratio (IV, Random, 95% CI) |
1.70 [1.35, 2.15] |
| 8.5.8 Vomiting |
7 |
1278 |
Risk Ratio (IV, Random, 95% CI) |
2.47 [0.82, 7.47] |
| 8.5.9 Upper abdominal pain |
1 |
107 |
Risk Ratio (IV, Random, 95% CI) |
442413.39 [0.00, 294025957312946900000000000000000000000000000000000000000000000000000000000000000000000000000.00] |
| 8.5.10 Decreased weight |
2 |
365 |
Risk Ratio (IV, Random, 95% CI) |
5.04 [0.59, 43.15] |
| 8.5.11 Gastrointestinal distress |
1 |
77 |
Risk Ratio (IV, Random, 95% CI) |
8103.08 [0.00, 1011052702371868400000000000000000000000000000000000000000000000000000000.00] |
| 8.5.12 Constipation |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
4.63 [0.23, 94.88] |
| 8.5.13 Oropharyngeal pain |
1 |
211 |
Risk Ratio (IV, Random, 95% CI) |
2.72 [0.00, 11653710777400273000000000000000000000000000000000000000000000000000000000000000000000000000000.00] |
| 8.5.14 Anorexia |
1 |
203 |
Risk Ratio (IV, Random, 95% CI) |
2.97 [0.61, 14.37] |
| 8.6 Cardiovascular system |
2 |
730 |
Risk Ratio (M‐H, Random, 95% CI) |
4.97 [1.09, 22.76] |
| 8.6.1 Epistaxis |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.6.2 Heart palpitations |
2 |
365 |
Risk Ratio (M‐H, Random, 95% CI) |
5.65 [0.67, 47.90] |
| 8.6.3 Chest pain |
1 |
211 |
Risk Ratio (M‐H, Random, 95% CI) |
6.43 [0.34, 123.02] |
| 8.7 Respiratory system |
2 |
673 |
Risk Ratio (M‐H, Random, 95% CI) |
1.29 [0.36, 4.68] |
| 8.7.1 Nasal congestion |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
0.92 [0.06, 14.52] |
| 8.7.2 Strep throat/sore throat |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.30, 26.09] |
| 8.7.3 Cough |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
0.46 [0.04, 5.00] |
| 8.7.4 Dyspnea |
1 |
211 |
Risk Ratio (M‐H, Random, 95% CI) |
2.76 [0.11, 66.91] |
| 8.8 Urinary system |
1 |
136 |
Risk Ratio (IV, Random, 95% CI) |
0.50 [0.05, 5.39] |
| 8.8.1 Urinary incontinence |
1 |
136 |
Risk Ratio (IV, Random, 95% CI) |
0.50 [0.05, 5.39] |
| 8.9 Skeletal and muscular system |
2 |
673 |
Risk Ratio (M‐H, Random, 95% CI) |
4.86 [0.83, 28.54] |
| 8.9.1 Ankle pain/strain |
1 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
Not estimable |
| 8.9.2 Muscle strain/pain |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
12.04 [0.69, 210.03] |
| 8.9.3 Toe fracture |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.9.4 Asthenia |
1 |
211 |
Risk Ratio (M‐H, Random, 95% CI) |
2.76 [0.11, 66.91] |
| 8.10 Skeletal and muscular system continuous outcomes |
1 |
82 |
Mean Difference (IV, Random, 95% CI) |
0.85 [0.79, 0.91] |
| 8.10.1 Somatic complaints |
1 |
82 |
Mean Difference (IV, Random, 95% CI) |
0.85 [0.79, 0.91] |
| 8.11 Immune system (including infections) |
9 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 8.11.1 Allergic rhinitis |
4 |
475 |
Risk Ratio (IV, Random, 95% CI) |
1.38 [0.35, 5.51] |
| 8.11.2 Fever |
2 |
91 |
Risk Ratio (IV, Random, 95% CI) |
1.39 [0.09, 20.56] |
| 8.11.3 Lymphadenitis |
2 |
296 |
Risk Ratio (IV, Random, 95% CI) |
3.93 [0.44, 35.11] |
| 8.11.4 Pharyngolaryngeal pain |
1 |
160 |
Risk Ratio (IV, Random, 95% CI) |
2.00 [0.19, 21.62] |
| 8.11.5 Pharyngitis |
4 |
754 |
Risk Ratio (IV, Random, 95% CI) |
0.71 [0.19, 2.62] |
| 8.11.6 Upper respiratory tract infection |
7 |
1245 |
Risk Ratio (IV, Random, 95% CI) |
1.21 [0.51, 2.86] |
| 8.11.7 Nasopharyngitis |
1 |
203 |
Risk Ratio (IV, Random, 95% CI) |
0.79 [0.22, 2.87] |
| 8.11.8 Influenza |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
4.63 [0.23, 94.87] |
| 8.11.9 Mouth ulcers/bad breath |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
4.63 [0.23, 94.87] |
| 8.11.10 Urinary tract infection |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.11.11 Otitis media (ear pain) |
1 |
0 |
Risk Ratio (IV, Random, 95% CI) |
Not estimable |
| 8.12 Integumentary system |
4 |
|
Risk Ratio (IV, Random, 95% CI) |
Subtotals only |
| 8.12.1 Rash |
3 |
362 |
Risk Ratio (IV, Random, 95% CI) |
1.49 [0.35, 6.37] |
| 8.12.2 Skin laceration |
1 |
167 |
Risk Ratio (IV, Random, 95% CI) |
2.96 [0.12, 71.75] |
| 8.12.3 Cellulitis |
1 |
154 |
Risk Ratio (IV, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.13 Sleep variability continuous outcomes |
1 |
512 |
Mean Difference (IV, Fixed, 95% CI) |
‐2.21 [‐5.23, 0.81] |
| 8.13.1 Actigraphic total sleep time |
1 |
52 |
Mean Difference (IV, Fixed, 95% CI) |
‐29.80 [‐60.86, 1.26] |
| 8.13.2 Actigraphic sleep onset latency |
1 |
52 |
Mean Difference (IV, Fixed, 95% CI) |
21.10 [1.33, 40.87] |
| 8.13.3 Actigraphic sleep efficiency |
1 |
52 |
Mean Difference (IV, Fixed, 95% CI) |
‐3.30 [‐8.16, 1.56] |
| 8.13.4 Polysonmnographic total sleep time |
1 |
252 |
Mean Difference (IV, Fixed, 95% CI) |
‐24.60 [‐52.20, 3.00] |
| 8.13.5 Polysomnographic sleep onset latency |
1 |
52 |
Mean Difference (IV, Fixed, 95% CI) |
8.40 [‐7.11, 23.91] |
| 8.13.6 Polysomnographic sleep efficiency |
1 |
52 |
Mean Difference (IV, Fixed, 95% CI) |
‐2.20 [‐6.34, 1.94] |
| 8.14 Sleep variability |
39 |
5810 |
Risk Ratio (IV, Random, 95% CI) |
1.81 [1.34, 2.44] |
| 8.14.1 Insomnia or sleep problems |
37 |
5499 |
Risk Ratio (IV, Random, 95% CI) |
1.88 [1.39, 2.56] |
| 8.14.2 Sleep efficiency (SEF) |
2 |
108 |
Risk Ratio (IV, Random, 95% CI) |
0.48 [0.02, 14.28] |
| 8.14.3 Initial insomnia |
1 |
203 |
Risk Ratio (IV, Random, 95% CI) |
0.59 [0.15, 2.42] |
| 8.15 Vital signs |
14 |
|
Std. Mean Difference (IV, Random, 95% CI) |
Subtotals only |
| 8.15.1 Diastolic blood pressure (mmHg) |
11 |
755 |
Std. Mean Difference (IV, Random, 95% CI) |
0.15 [‐0.04, 0.34] |
| 8.15.2 Systolic blood pressure (mmHg) |
11 |
755 |
Std. Mean Difference (IV, Random, 95% CI) |
0.05 [‐0.15, 0.26] |
| 8.15.3 Pulse or heart rate (bpm) |
14 |
939 |
Std. Mean Difference (IV, Random, 95% CI) |
0.43 [0.23, 0.64] |
| 8.16 Physical parameters |
6 |
576 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.04 [‐0.20, 0.13] |
| 8.16.1 Height (cm) |
1 |
46 |
Std. Mean Difference (IV, Random, 95% CI) |
0.20 [‐0.38, 0.78] |
| 8.16.2 Weight |
6 |
530 |
Std. Mean Difference (IV, Random, 95% CI) |
‐0.06 [‐0.23, 0.11] |
| 8.17 Other (including drug toxicity) |
2 |
1443 |
Risk Ratio (M‐H, Random, 95% CI) |
3.25 [0.99, 10.62] |
| 8.17.1 Growth hormone deficiency |
1 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
Not estimable |
| 8.17.2 Eye pain |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.17.3 Carious teeth |
1 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
Not estimable |
| 8.17.4 Foreign body swallowed |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.17.5 Bug bites/bee stings |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
4.63 [0.23, 94.87] |
| 8.17.6 Sunburn |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.17.7 Finger laceration |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
2.78 [0.11, 67.14] |
| 8.17.8 Flat affect (lack of emotional expression) |
1 |
154 |
Risk Ratio (M‐H, Random, 95% CI) |
4.63 [0.23, 94.87] |
| 8.17.9 Peripheral oedema |
1 |
211 |
Risk Ratio (M‐H, Random, 95% CI) |
2.76 [0.11, 66.91] |
