Research and analysis
Table 2a: Effects on IQ/Cognitive Effects
Updated 7 January 2021
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| IQ/ Cognitive Effects | ||||||||
|---|---|---|---|---|---|---|---|---|
| Not set | Carbamazepine | Lamotrigine | Levetiracetam | Oxcarbazepine | Phenobarbital | Phenytoin | Topiramate | Valproate |
| Meta-analyses | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Veroniki et al 2017b | OR 2.07 (0.82, 5.48) | OR 0.93 (0.09, 5.10) | OR 3.42 (0.65, 16.40) | - | OR 1.36 (0.18, 7.02) | OR 2.55 (0.72, 8.55) | OR 3.14 (0.45, 16.53) | OR 7.40 (3.00, 18.46) |
| Not set | Not set | N=43 | Not set | Not set | Not set | Not set | Not set | Not set |
| Cognitive Developmental Delay | N=238 | Not set | Not set | Not set | N=12 | N=111 | N= | N= |
| Bromley et al 2014 | IQ | IQ | - | - | 86.2 (SD 11) | PHT (n=29) mean 90.3 (95% CI 77 to 103) vs WWE control (n=32) mean 92.3 (95% CI 81 to 103) NS* | mean 96.33 SD 10.37) | MD-8.94 (-11.96, -5.92), P<0.00001, I2=88% |
| Not set | MD -0.03 (95% CI –3.08 to 3.01) Vs WWOE | mean 105.56, SD 12.49 versus control | Not set | Not set | vs WWOE | Not set | Vs WWOE | Vs WWOE |
| IQ mean (SD) | N=150 | mean 108.71, SD 10.20, P>0.05 | Not set | Not set | 93 (SD 14.4) | Cognitive dysfunction | mean 111.39 (SD 12.20), P=0.005 | N=76 |
| Not set | MD 1.84 (95% CI -2.13 to 5.80) Vs WWE | N=41 | Not set | Not set | N=41 | OR 1.37 (95% CI 0.38 to 5.0) | N=9 | Not set |
| Verbal IQ (VIQ) | N=163 | Not set | Not set | Not set | Not set | PHT (n=12) | Not set | MD-8.17 (-12.80, -3.55), P=0.005, I2=27% |
| Not set | Not set | Verbal IQ and Performance IQ also did not significantly differ to control population | Not set | Not set | Not set | Not set | Not set | Vs WWE |
| Performance IQ (PIQ) | Vs general population controls | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | VIQ | Not set | Not set | Not set | Not set | Not set | Not set | VIQ |
| Not set | MD -1.81 (95% CI -4.94 to 1.33 | Not set | Not set | Not set | Not set | Not set | Not set | MD-11.39 (-14.68, -8.10), P<0.00001, I2=0% vs general population |
| Not set | PIQ | Not set | Not set | Not set | Not set | Not set | Not set | N=64 |
| Not set | MD 1.27 (95% CI -1.55 to 4.09) | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | N=136 | Not set | Not set | Not set | Not set | Not set | Not set | PIQ |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | MD-10.48 (-13.94, -7.02), P<0.00001, I2=68% |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | N=64 |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Banach et al 2010 | Wechsler scale | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Statistically significantly lower PIQ in CBZ (p<0.002) compared all control group; | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | No statistically significant difference for either VIQ or FSIQ compared to all control group | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Wechsler Scale PIQ | N=151 | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Bayley or McCarthy scale FSIQ | Bayley or McCarthy scales | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | FSIQ no statistically significant different; CBZ vs control group | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | (98 vs 102, p=0.3) | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | N=83 | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Pregnancy Registries | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Gopinath et al. 2015 | CBZ mono (40) | LMT mono (1) | Not set | Not set | PB mono (n=22) | PHT mono (n=11) | - | VPA mono (36) |
| Not set | 82.2 (13.9) | 89 | Not set | Not set | 74.5 (14) | 82.6 (13.5) | Not set | 82.8 (12.4) |
| Wechsler scale | vs | vs | Not set | Not set | vs | vs | Not set | vs |
| Not set | 80.2 (13.4); | 80.8 (13.6); | Not set | Not set | 82.5 (13); | 80.7 (13.7); | Not set | 77 (15.3); |
| Full Scale IQ | p=0.449 | p=0.551 | Not set | Not set | p=0.013 | p=0.656 | Not set | p=0.190 |
| Mean (SD) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | CBZ all (76) | LMT all (4) | Not set | Not set | PB all (n=59) | PHT all (n=39) | Not set | VPA all (53) |
| Not set | 77 (15.2) | mean 71.3 (17.9) | Not set | Not set | 73.5 (14.4) | 74.9 (14.8) | Not set | 80.2 (12.7) |
| Not set | vs | vs | Not set | Not set | vs | vs | Not set | vs |
| Not set | 78.5 (1.4); | 78.1 (14.6); p=0.356 | Not set | Not set | 80 (14.4); | 78.7 (14.5); | Not set | 77 (15.3); |
| Not set | p=0.466 | Not set | Not set | Not set | p=0.05 | p=0.153 | Not set | p=0.313 |
| Huber-Mollema et a l2020 | FSIQ | FSIQ | FSIQ | Not set | Not set | Not set | Not set | FSIQ |
| Not set | 105.3 (13.7) | 109.2 (15.0) | 110.8 (14.8) | Not set | Not set | Not set | Not set | 103.2 (14.8) |
| Wechsler Intelligence Scale | B 5.6 (SE 3.9) (95% -2.2 to 13.4), P=0.157 | B 7.5 (SE 3.5) (95% 0.6 to 14.4), P=0.033 | B 7.7 (SE 4.1) (95% --0.4 to 15.8), P=0.064 | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Full-Scale IQ (FSIQ) | VIQ | VIQ | VIQ | Not set | Not set | Not set | Not set | VIQ |
| Not set | 106.2 (14.2) | 109.7 (15.7) | 114.0 (13.1) | Not set | Not set | Not set | Not set | 100.6 (14.9) |
| Verbal IQ (VIQ) | B 9.1 (SE 4.0) (95% 1.3 to 17.0), P=0.023 | B 10.3 (SE 3.5) (95% 3.4 to 17.3), P=0.004 | B 13.4 (SE 4.2) (95% 5.2 to 21.6), P=0.002 | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | PIQ |
| Performance IQ (PIQ) | PIQ | PIQ | PIQ | Not set | Not set | Not set | Not set | 105.3 (17.0) |
| Not set | 102.8 (15.5) | 106.0 (14.9) | 104.4 (14.8) | Not set | Not set | Not set | Not set | Not set |
| Processing Speed Index | B 0.1 (SE 4.3) (95% -8.3 to 8.6), P=0.973 | B 2.3 (SE 3.8) (95% -5.3 to 9.8), P=0.551 | B -0.6 (SE 4.5) (95% -9.5 to 8.3), P=0.901 | Not set | Not set | Not set | Not set | PSI |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 107.4 (18.6) |
| Mean (SD) | PSI | PSI | PSI | Not set | Not set | Not set | Not set | Not set |
| Not set | 108.7 (12.1) | 111.0 (14.4) | 111.2 (16.2) | Not set | Not set | Not set | Not set | Not set |
| Individual AED | B 5.1 (SE 4.2) (95% -3.3 to 13.5), P=0.229 | B 6.3 (SE 3.8) (95% -1.1 to 13.7), P=0.097 | B 4.9 (SE 4.4) (95% -3.9 to 3.6), P=0.275 | Not set | Not set | Not set | Not set | N=22 |
| Vs | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| VPA | N=32 | N=82 | N=25 | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Kerala Pregnancy Registry | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Thomas et al 2007 | FSIQ | - | - | - | FSIQ | FSIQ | - | FSIQ |
| Not set | 83.6 (30.0); p=0.22 (all) | Not set | Not set | Not set | 84.9 (20.1); p=0.35 (all) | 87.6 (19.0); p=0.96 (all) | Not set | 87.2 (29.8); p=0.90 (all) |
| Full Scale IQ (FSIQ- adaptation of Wechsler Intelligence Scale) | 91.9 (21.7); p=0.86 (mono) | Not set | Not set | Not set | 86.2 (11.0); p=0.07 (mono) | 97.8 (9.9) p=0.43 (mono) | Not set | 98.5 (13.5); p=0.12 (mono) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Malayalam Language Test (MLT) – local proficiency test for language | MLT | Not set | Not set | Not set | MLT | MLT | Not set | MLT |
| Not set | 71.5 (22.4); p=0.44 (all) | Not set | Not set | Not set | 71.8 (14.9); p=0.47 (all) | 71.1 (15.7); p=0.51 (all) | Not set | 73.7 (21.1); p=0.95 (all) |
| vs | 74.9 (21.0); p=0.87 (mono) | Not set | Not set | Not set | 70.6 (8.5); p=0.146 (mono) | 76.0 (10.7); p=0.92 (mono) | Not set | 81.5 (11.9); p=0.09 (mono) |
| Age Matched Controls | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | N=28 (all) | Not set | Not set | Not set | N=32 (all) | N=18 (all) | Not set | 19 VPA (all) |
| Not set | N=14 (mono) | Not set | Not set | Not set | N=14 (mono) | N=5 (mono) | Not set | 12 VPA (mono) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Prospective studies | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Cohen et al 2019 | IQ | IQ | - | - | - | IQ | - | IQ |
| Not set | 106.2 (95% CI 103.1 to 109.3); | 108.4 (95% CI 105.5 to 111.3); | Not set | Not set | Not set | 107.4 (95% CI 103.3 to 111.4); | Not set | 100.8 (95% CI 97.2 to 104.3); |
| Standardised mean of 6 years IQ (95% CI) | Effect -5.4 (-10.4 to -0.4); p=0.0370 | Effect -3.2 (-8.1 to -1.8); p=0.2111 | Not set | Not set | Not set | Effect -4.2 (-9.8 to 1.4); p=0.1467 | Not set | Effect -10.8 (-16 to -5.6); p<0.0001 |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Attention/concentration | Attention/concentration | Attention/concentration | Not set | Not set | Not set | Attention/concentration | Not set | Attention/concentration |
| Not set | 101.2 (96.8, 105.5) | 98.2 (94.2, 102.3) | Not set | Not set | Not set | 98 (92.5, 103.6) | Not set | 94.1 (89.1, 99.1) |
| Verbal immediate | Effect -3.1 (-8.7, 2.6) | Effect -6 (-11.5, -0.5) | Not set | Not set | Not set | Effect -6.2 (-12.7, 0.3) | Not set | Effect -10.2 (-16.3, -4.1) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Verbal delayed | Verbal immediate | Verbal immediate | Not set | Not set | Not set | Verbal immediate | Not set | Verbal immediate |
| Not set | 103.2 (99.4, 107) | 103.1 (99.6, 106.7) | Not set | Not set | Not set | 100.8 (96, 105.6) | Not set | 94.5 (90, 98.9) |
| Delayed recognition | Effect -1.6 (-6.5, 3.3) | Effect -1.7 (-6.5, 3.1) | Not set | Not set | Not set | Effect -4 (-9.7, 1.6) | Not set | Effect -10.4 (-15.8, -5.0) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Visual immediate | Verbal delayed | Verbal delayed | Not set | Not set | Not set | Verbal delayed | Not set | Verbal delayed |
| Not set | 103.8 (99.5, 108.1) | 103.6 (99.6, 107.6) | Not set | Not set | Not set | 99.1 (93.7, 104.5) | Not set | 92.2 (87.2, 97.3) |
| Visual delayed | Effect 0 (-5.6, 5.5) | Effect -0.3 (-5.6, 5.1) | Not set | Not set | Not set | Effect -4.8 (-11.1, 1.6) | Not set | Effect -11.6 (-17.7, -5.5) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Learning | Delayed recognition | Delayed recognition | Not set | Not set | Not set | Delayed recognition | Not set | Delayed recognition |
| Not set | 101.5 (97.8, 105.2) | 103.1 (99.7, 106.6) | Not set | Not set | Not set | 99.3 (94.6, 103.9) | Not set | 90.4 (86, 94.7) |
| Not set | Effect -3.8 (-8.6, 1) | Effect -2.2 (-6.8, 2.5) | Not set | Not set | Not set | Effect -6 (-11.5, -0.5) | Not set | Effect -14.9 (-20.2, -9.6) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Visual immediate | Visual immediate | Not set | Not set | Not set | Visual immediate | Not set | Visual immediate |
| Not set | 98.6 (95, 102.1) | 100.6 (97.3, 103.9) | Not set | Not set | Not set | 97.3 (92.8, 101.8) | Not set | 94.4 (90.3, 98.5) |
| Not set | Effect -3.1 (-7.7, 1.5) | Effect -1.1 (-5.6, 3.4) | Not set | Not set | Not set | Effect -4.4 (-9.7, 0.9) | Not set | Effect -7.3 (-12.3, -2.2) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Visual delayed | Visual delayed | Not set | Not set | Not set | Visual delayed | Not set | Visual delayed |
| Not set | 103.4 (99.7, 107) | 105.3 (101.9, 108.7) | Not set | Not set | Not set | 99.4 (94.8, 104.1) | Not set | 95.2 (90.9, 99.4) |
| Not set | Effect 0.2 (-4.5, 4.9) | Effect -2.2 (-2.4, 6.7) | Not set | Not set | Not set | Effect -3.7 (-9.1, 1.7) | Not set | Effect -8 (-13.2, -2.8) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Learning | Learning | Not set | Not set | Not set | Learning | Not set | Learning |
| Not set | 98.4 (94.6, 102.1) | 98 (94.5, 101.5) | Not set | Not set | Not set | 94.7 (89.9, 99.4) | Not set | 90.2 (85.9, 94.6) |
| Not set | Effect-5.1 (-10, -0.3) | Effect-5.5 (-10.2, -0.8) | Not set | Not set | Not set | Effect-8.8 (-14.4, -3.3) | Not set | Effect-13.3 (-18.6, -8) |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | N=61 | N=73 | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | N=39 | Not set | N=48 |
| Titze et al 2008 | Not set | Not set | Not set | Not set | adjusted total IQ: 98.0 SD11.9 | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | versus control | Not set | Not set | Not set |
| Wechsler Adult Intelligence Scale | Not set | Not set | Not set | Not set | 105.4 SD11.0, p=0.037 | Not set | Not set | Not set |
| (WAIS) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | N=14 (3 mono) | Not set | Not set | Not set |
| Scolnik et al 1994 | Global IQ | Not set | Not set | Not set | Not set | Global IQ | Not set | Not set |
| Not set | 111.5 (19.7) | Not set | Not set | Not set | Not set | 103.1 (25.2) | Not set | Not set |
| Global IQ | Vs 114.9 (13.3) | Not set | Not set | Not set | Not set | Vs 113.4 (13.1) | Not set | Not set |
| Not set | NS | Not set | Not set | Not set | Not set | Significant difference | Not set | Not set |
| (Bayley or McCarthy Scale) | Not set | Not set | Not set | Not set | Not set | -10.6 (27.9) | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Reynell verbal comprehension | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Mean (SE) | 0.72 (1.4) | Not set | Not set | Not set | Not set | Reynell verbal comprehension | Not set | Not set |
| Not set | Vs 1.05 (0.81) | Not set | Not set | Not set | Not set | 0.2 (1.6) | Not set | Not set |
| AED | NS | Not set | Not set | Not set | Not set | Vs 1.1 (0.95) | Not set | Not set |
| Vs | Not set | Not set | Not set | Not set | Not set | Significant difference | Not set | Not set |
| Control | Not set | Not set | Not set | Not set | Not set | -0.47 (1.2) | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Others | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Reinisch et al 1995 | - | - | - | - | WAIS | - | - | - |
| Retrospective cohort study | Not set | Not set | Not set | Not set | VIQ 100.69 (14.94) | Not set | Not set | - |
| Denmark | Not set | Not set | Not set | Not set | Vs predicted 107.86 (6.38) | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | equal to -7.17 (adjusted SE, 3.99; adjusted t, -1.79; df, 37; P<.04) | Not set | Not set | Not set |
| Wechsler Adult Intelligence Scale | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| (WAIS) | Not set | Not set | Not set | Not set | IBPP | Not set | Not set | Not set |
| Verbal IQ (VIQ) | Not set | Not set | Not set | Not set | mean difference -4.77; | Not set | Not set | Not set |
| Mean (SD) | Not set | Not set | Not set | Not set | adjusted SE, 1.63; adjusted t, -2.92; df, 85; P<.002). | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Danish Military Board Intelligence Test BPP scores | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| (IBPP) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Hanson et al 1976 | Not set | Not set | Not set | Not set | Not set | PHT | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | 91.7 (17.29) | Not set | Not set |
| WISC full scale IQ at 7 years | Not set | Not set | Not set | Not set | Not set | Vs | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Control | Not set | Not set |
| Mean (SD) | Not set | Not set | Not set | Not set | Not set | 96.83 (15.5); t=2,01, p<0.05 | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | N=83 | Not set | Not set |
| Rihtman et al | Not set | Not set | Not set | Not set | Not set | Not set | Fluid reasoning (p=0.005) | Not set |
| Israeli Teratogen Information Service | Not set | Not set | Not set | Not set | Not set | Not set | Quantitative reasoning (p=0.002) | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Visual-spatial (p=0.003) | Not set |
| IQ tests | Not set | Not set | Not set | Not set | Not set | Not set | Verbal IQ (p=0.017), non-verbal IQ (=0.011) | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | General IQ (p=0.005) | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 9 TPM exposures | Not set |