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. 2016 Feb 5;2016(2):CD008919. doi: 10.1002/14651858.CD008919.pub2

Comparison 1. ADJUNCTIVE ANTIOXIDANTS versus PLACEBO.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 Global state: No clinically important response (20% improvement PANSS) 3 229 Risk Ratio (M‐H, Random, 95% CI) 0.77 [0.53, 1.12]
1.1 allopurinol ‐ short term 2 94 Risk Ratio (M‐H, Random, 95% CI) 0.69 [0.36, 1.32]
1.2 n‐acetyl cysteine ‐ medium term 1 135 Risk Ratio (M‐H, Random, 95% CI) 1.01 [0.53, 1.92]
2 Leaving the study early: 1a. Short term 16 1584 Risk Ratio (M‐H, Random, 95% CI) 0.73 [0.48, 1.11]
2.1 allopurinol 4 388 Risk Ratio (M‐H, Random, 95% CI) 0.83 [0.55, 1.24]
2.2 DHEA 1 32 Risk Ratio (M‐H, Random, 95% CI) 0.6 [0.17, 2.10]
2.3 ginkgo biloba 4 857 Risk Ratio (M‐H, Random, 95% CI) 0.42 [0.17, 1.03]
2.4 n‐acetyl cysteine 1 46 Risk Ratio (M‐H, Random, 95% CI) 1.0 [0.15, 6.51]
2.5 selegiline 3 153 Risk Ratio (M‐H, Random, 95% CI) 5.22 [0.90, 30.31]
2.6 vitamin C 1 40 Risk Ratio (M‐H, Random, 95% CI) 0.25 [0.03, 2.05]
2.7 vitamin E 2 68 Risk Ratio (M‐H, Random, 95% CI) 0.97 [0.06, 14.48]
3 Leaving the study early: 1b. Medium term 1 140 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.67, 1.48]
3.1 n‐acetyl cysteine 1 140 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.67, 1.48]
4 Leaving the study early: 1c. Long term 2 195 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.59, 1.35]
4.1 vitamin E 2 195 Risk Ratio (M‐H, Random, 95% CI) 0.90 [0.59, 1.35]
5 Mental state: 1a. General ‐ average overall endpoint score ‐ short term (BPRS total, high = worse) 8 843 Mean Difference (IV, Random, 95% CI) ‐3.20 [‐5.63, ‐0.78]
5.1 ginkgo biloba 3 663 Mean Difference (IV, Random, 95% CI) ‐2.74 [‐5.29, ‐0.20]
5.2 selegiline 3 111 Mean Difference (IV, Random, 95% CI) ‐0.31 [‐4.03, 3.41]
5.3 vitamin C 1 40 Mean Difference (IV, Random, 95% CI) ‐9.66 [‐13.27, ‐6.05]
5.4 vitamin E 1 29 Mean Difference (IV, Random, 95% CI) ‐7.92 [‐17.20, 1.36]
6 Mental state: 1b. General ‐ average overall endpoint score ‐ short term (PANSS total, high = worse) 7 584 Mean Difference (IV, Random, 95% CI) ‐6.00 [‐10.35, ‐1.65]
6.1 allopurinol 3 329 Mean Difference (IV, Random, 95% CI) ‐6.91 [‐15.86, 2.04]
6.2 ginkgo biloba 1 157 Mean Difference (IV, Random, 95% CI) ‐3.30 [‐6.51, ‐0.09]
6.3 selegiline 2 56 Mean Difference (IV, Random, 95% CI) ‐2.97 [‐15.68, 9.74]
6.4 n‐acetyl cysteine 1 42 Mean Difference (IV, Random, 95% CI) ‐12.86 [‐19.82, ‐5.90]
7 Mental state: 1c. General ‐ average overall endpoint score ‐ medium term (PANSS total, high = worse) 1 135 Mean Difference (IV, Random, 95% CI) ‐1.71 [‐7.55, 4.13]
7.1 n‐acetyl cysteine 1 135 Mean Difference (IV, Random, 95% CI) ‐1.71 [‐7.55, 4.13]
8 Mental state: 1d. General ‐ average overall endpoint score ‐ long term (BPRS total, high = worse) 1   Mean Difference (IV, Random, 95% CI) Subtotals only
8.1 vitamin E 1 104 Mean Difference (IV, Random, 95% CI) 1.20 [‐2.47, 4.87]
9 Mental state: 2a. Specific ‐ average negative symptom endpoint score ‐ short term (PANSS negative, high = worse) 9 653 Std. Mean Difference (IV, Random, 95% CI) ‐0.38 [‐0.77, 0.00]
9.1 selegiline 3 111 Std. Mean Difference (IV, Random, 95% CI) ‐0.54 [‐1.76, 0.68]
9.2 allopurinol 3 317 Std. Mean Difference (IV, Random, 95% CI) ‐0.37 [‐0.98, 0.23]
9.3 ginkgo biloba 1 157 Std. Mean Difference (IV, Random, 95% CI) ‐0.17 [‐0.49, 0.14]
9.4 n‐acetyl cysteine 1 44 Std. Mean Difference (IV, Random, 95% CI) ‐1.10 [‐1.74, ‐0.47]
9.5 DHEA 1 24 Std. Mean Difference (IV, Random, 95% CI) 0.63 [‐0.20, 1.45]
10 Mental state: 2b. Specific ‐ average negative symptom endpoint score ‐ short term (SANS, high = worse) 3 667 Mean Difference (IV, Random, 95% CI) ‐7.46 [‐12.46, ‐2.46]
10.1 ginkgo biloba 3 667 Mean Difference (IV, Random, 95% CI) ‐7.46 [‐12.46, ‐2.46]
11 Mental state: 2c. Specific ‐ average negative symptom endpoint score ‐ medium term (PANSS negative, high = worse) 1 135 Mean Difference (IV, Random, 95% CI) ‐2.33 [‐4.24, ‐0.42]
11.1 n‐acetyl cysteine 1 135 Mean Difference (IV, Random, 95% CI) ‐2.33 [‐4.24, ‐0.42]
12 Mental state: 2d. Specific ‐ average positive symptom endpoint score ‐ short term (PANSS positive, high = worse) 8 611 Mean Difference (IV, Random, 95% CI) ‐0.96 [‐2.50, 0.58]
12.1 allopurinol 3 317 Mean Difference (IV, Random, 95% CI) ‐3.55 [‐8.24, 1.13]
12.2 DHEA 1 24 Mean Difference (IV, Random, 95% CI) 3.60 [‐1.30, 8.50]
12.3 ginkgo biloba 1 157 Mean Difference (IV, Random, 95% CI) ‐1.20 [‐2.31, ‐0.09]
12.4 n‐acetyl cysteine 1 42 Mean Difference (IV, Random, 95% CI) ‐1.14 [‐3.57, 1.29]
12.5 selegiline 2 71 Mean Difference (IV, Random, 95% CI) 0.57 [‐2.30, 3.45]
13 Mental state: 2e. Specific ‐ average positive symptom endpoint score ‐ short term (SAPS, high = worse) 2 151 Mean Difference (IV, Random, 95% CI) ‐5.06 [‐7.52, ‐2.59]
13.1 ginkgo biloba 2 151 Mean Difference (IV, Random, 95% CI) ‐5.06 [‐7.52, ‐2.59]
14 Mental state: 2f. Secific ‐ average positive symptom endpoint score ‐ medium term (PANSS positive, high = worse) 1 135 Mean Difference (IV, Random, 95% CI) 0.47 [‐1.43, 2.37]
14.1 n‐acetyl cysteine 1 135 Mean Difference (IV, Random, 95% CI) 0.47 [‐1.43, 2.37]
15 General functioning: 1a. General ‐ average overall endpoint score ‐ short term (GAS total, high = worse) 2 52 Mean Difference (IV, Random, 95% CI) ‐1.11 [‐8.07, 5.86]
15.1 DHEA 1 24 Mean Difference (IV, Random, 95% CI) ‐7.40 [‐19.80, 5.00]
15.2 selegiline 1 28 Mean Difference (IV, Random, 95% CI) 0.90 [‐3.25, 5.05]
16 General functioning: 1b. General ‐ average overall endpoint score ‐ medium term (GAS total, high = worse) 1   Mean Difference (IV, Random, 95% CI) Subtotals only
16.1 n‐acetyl cysteine 1 135 Mean Difference (IV, Random, 95% CI) 2.84 [‐2.09, 7.77]
17 General functioning: 1c. General ‐ average overall endpoint score ‐ long term (GAS total, high = worse) 1   Mean Difference (IV, Random, 95% CI) Subtotals only
17.1 vitamin E 1 104 Mean Difference (IV, Random, 95% CI) 0.10 [‐5.60, 5.80]
18 Adverse effects: 1. Serious (any time point) 3   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
18.1 any serious adverse effect 3 234 Risk Ratio (M‐H, Random, 95% CI) 0.65 [0.19, 2.27]
18.2 myocardial infarction 1 59 Risk Ratio (M‐H, Random, 95% CI) 2.72 [0.12, 64.14]
18.3 neutropenia 1 59 Risk Ratio (M‐H, Random, 95% CI) 0.30 [0.01, 7.13]
18.4 pneumonia 2 94 Risk Ratio (M‐H, Random, 95% CI) 2.78 [0.30, 25.75]
18.5 seizure 1 35 Risk Ratio (M‐H, Random, 95% CI) 0.32 [0.01, 7.26]
19 Adverse effects: 2. Various ‐ less serious 6   Risk Ratio (M‐H, Random, 95% CI) Subtotals only
19.1 allergy ‐ rash or other dermatological problems 4 280 Risk Ratio (M‐H, Random, 95% CI) 1.06 [0.61, 1.84]
19.2 cardiovascular ‐ dizziness 2 82 Risk Ratio (M‐H, Random, 95% CI) 1.17 [0.46, 2.96]
19.3 cardiovascular ‐ systemic hypertension 2 82 Risk Ratio (M‐H, Random, 95% CI) 3.30 [0.99, 11.04]
19.4 central nervous system ‐ agitation 1 40 Risk Ratio (M‐H, Random, 95% CI) 2.5 [0.55, 11.41]
19.5 central nervous system ‐ appetite increase 3 128 Risk Ratio (M‐H, Random, 95% CI) 1.0 [0.54, 1.87]
19.6 central nervous system ‐ headache 4 281 Risk Ratio (M‐H, Random, 95% CI) 0.99 [0.60, 1.64]
19.7 central nervous system ‐ insomnia 1 40 Risk Ratio (M‐H, Random, 95% CI) 2.5 [0.55, 11.41]
19.8 central nervous system ‐ sedation 2 88 Risk Ratio (M‐H, Random, 95% CI) 1.34 [0.70, 2.59]
19.9 central nervous system ‐ tremor 2 86 Risk Ratio (M‐H, Random, 95% CI) 0.70 [0.32, 1.54]
19.10 gastrointestinal ‐ abdominal pain 1 40 Risk Ratio (M‐H, Random, 95% CI) 2.0 [0.41, 9.71]
19.11 gastrointestinal ‐ nausea 4 281 Risk Ratio (M‐H, Random, 95% CI) 1.04 [0.67, 1.62]
20 Adverse effects: 3. Average score (TESS endpoint, high = worse) 1 109 Mean Difference (IV, Fixed, 95% CI) ‐0.90 [‐2.34, 0.54]
21 Laboratory data (serum tests) ‐ short term 3   Std. Mean Difference (IV, Random, 95% CI) Subtotals only
21.1 MDA levels 1 40 Std. Mean Difference (IV, Random, 95% CI) ‐2.18 [‐2.98, ‐1.38]
21.2 SOD levels 2 123 Std. Mean Difference (IV, Random, 95% CI) 0.27 [‐0.56, 1.10]