TABLE 2.
Meta-analysis of safety outcomes of lacosamide vs. placebo or other ASMs.
| Group | Study type | Studies | n/N1 | n/N2 | Heterogeneity | RR (95%CI) | P | |
|---|---|---|---|---|---|---|---|---|
| Nervous system | ||||||||
| Dizziness | LCM vs. TPM | Cohort study | 1 | 5/160 | 0/135 | Not applicable | 9.29 (0.52, 166.53) | 0.13 |
| — | LCM vs. ZNS | Cohort study | 2 | 12/179 | 0/152 | P = 0.97; I 2 = 0% | 9.32 (1.26, 68.84) | 0.03 |
| — | LCM vs. LEV | Cohort study | 2 | 7/182 | 3/160 | P = 0.11; I 2 = 61% | 2.10 (0.58, 7.54) | 0.26 |
| — | LCM vs. PGB | Cohort study | 1 | 5/160 | 0/135 | Not applicable | 9.29 (0.52, 166.53) | 0.13 |
| — | LCM vs. PER | Cohort study | 1 | 16/70 | 11/70 | Not applicable | 1.45 (0.73, 2.91) | 0.29 |
| — | LCM vs. CBZ | RCT | 1 | 8/64 | 10/62 | Not applicable | 0.74 (0.27, 2.03) | 0.56 |
| — | LCM vs. placebo | RCT | 4 | 383/1,307 | 46/548 | P = 0.68; I 2 = 0% | 3.28 (2.45, 4.38) | <0.001 |
| — | — | Cohort study | 1 | 37/385 | 5/179 | Not applicable | 3.70 (1.48, 9.25) | 0.005 |
| Sedation | LCM vs. TPM | Cohort study | 1 | 5/160 | 0/135 | Not applicable | 9.29 (0.52, 166.53) | 0.13 |
| — | LCM vs. ZNS | Cohort study | 1 | 5/160 | 14/141 | Not applicable | 0.31 (0.12, 0.85) | 0.02 |
| — | LCM vs. LEV | Cohort study | 1 | 5/160 | 20/136 | Not applicable | 0.21 (0.08, 0.55) | 0.001 |
| — | LCM vs. PGB | Cohort study | 1 | 5/160 | 18/135 | Not applicable | 0.23 (0.09, 0.61) | 0.003 |
| Somnolence/drowsiness | LCM vs. PER | Cohort study | 1 | 6/70 | 29/70 | Not applicable | 0.21 (0.09, 0.47) | <0.001 |
| — | LCM vs. CBZ | RCT | 1 | 1/64 | 8/62 | Not applicable | 0.11 (0.01, 0.99) | 0.04 |
| — | LCM vs. placebo | RCT | 3 | 95/985 | 20/385 | P = 0.44; I 2 = 0% | 1.79 (1.12, 2.86) | 0.01 |
| — | — | Cohort study | 1 | 10/358 | 2/179 | Not applicable | 2.50 (0.55, 11.29) | 0.23 |
| Headache | LCM vs. TPM | Cohort study | 1 | 4/160 | 7/135 | Not applicable | 0.48 (0.14, 1.61) | 0.24 |
| — | LCM vs. ZNS | Cohort study | 1 | 4/160 | 6/141 | Not applicable | 0.59 (0.17, 2.04) | 0.40 |
| — | LCM vs. LEV | Cohort study | 1 | 4/160 | 4/136 | Not applicable | 0.85 (0.22, 3.33) | 0.82 |
| — | LCM vs. PGB | Cohort study | 1 | 4/160 | 0/135 | Not applicable | 7.60 (0.41, 139.95) | 0.17 |
| — | LCM vs. CBZ | RCT | 1 | 8/64 | 9/62 | Not applicable | 0.84 (0.30, 2.34) | 0.74 |
| — | LCM vs. placebo | RCT | 4 | 164/1,307 | 44/548 | P = 0.65; I 2 = 0% | 1.49 (1.08, 2.04) | 0.01 |
| Diplopia/double version | LCM vs. TPM | Cohort study | 1 | 3/160 | 3/135 | Not applicable | 0.84 (0.17, 4.11) | 0.83 |
| — | LCM vs. ZNS | Cohort study | 1 | 3/160 | 0/141 | Not applicable | 6.17 (0.32, 118.50) | 0.23 |
| — | LCM vs. LEV | Cohort study | 1 | 3/160 | 0/136 | Not applicable | 5.96 (0.31, 114.31) | 0.24 |
| — | LCM vs. PGB | Cohort study | 1 | 3/160 | 5/135 | Not applicable | 0.51 (0.12, 2.08) | 0.35 |
| — | LCM vs. placebo | RCT | 2 | 60/643 | 4/260 | P = 0.66; I 2 = 0% | 5.86 (2.15, 15.94) | <0.001 |
| — | — | Cohort study | 1 | 7/358 | 1/179 | Not applicable | 3.50 (0.43, 28.23) | 0.24 |
| Ataxia/balance disorder | LCM vs. TPM | Cohort study | 1 | 4/160 | 0/135 | Not applicable | 7.60 (0.41, 139.95) | 0.17 |
| — | LCM vs. ZNS | Cohort study | 1 | 4/160 | 3/141 | Not applicable | 1.18 (0.27, 5.16) | 0.83 |
| — | LCM vs. LEV | Cohort study | 1 | 4/160 | 0/136 | Not applicable | 7.66 (0.42, 140.98) | 0.17 |
| — | LCM vs. PGB | Cohort study | 1 | 4/160 | 9/135 | Not applicable | 0.38 (0.12, 1.19) | 0.10 |
| — | LCM vs. PER | Cohort study | 1 | 3/70 | 4/70 | Not applicable | 0.75 (0.17, 3.23) | 0.70 |
| — | LCM vs. placebo | RCT | 3 | 88/944 | 6/364 | P = 0.83; I 2 = 0% | 5.03 (2.23, 11.37) | <0.001 |
| — | Cohort study | 1 | 6/358 | 1/179 | Not applicable | 3.00 (0.36, 24.73) | 0.31 | |
| Nystagmus | LCM vs. placebo | RCT | 2 | 45/622 | 10/201 | P = 0.51; I 2 = 0% | 1.45 (0.74, 2.82) | 0.28 |
| Paresthesia/cognitive side effect | LCM vs. TPM | Cohort study | 1 | 0/160 | 8/135 | Not applicable | 0.05 (0.00, 0.85) | 0.04 |
| — | LCM vs. ZNS | Cohort study | 2 | 6/179 | 4/152 | Not applicable | 1.27 (0.37, 4.43) | 0.70 |
| Fatigue | LCM vs. TPM | Cohort study | 1 | 0/160 | 17/135 | Not applicable | 0.02 (0.00, 0.40) | 0.009 |
| — | LCM vs. ZNS | Cohort study | 2 | 4/179 | 2/152 | Not applicable | 1.70 (0.32, 9.14) | 0.54 |
| — | LCM vs. LEV | Cohort study | 1 | 0/160 | 4/136 | Not applicable | 0.09 (0.01, 1.74) | 0.11 |
| — | LCM vs. PGB | Cohort study | 1 | 0/160 | 6/135 | Not applicable | 0.06 (0.00, 1.14) | 0.06 |
| — | LCM vs. PER | Cohort study | 1 | 0/70 | 4/70 | Not applicable | 0.11 (0.01, 2.03) | 0.14 |
| — | LCM vs. CBZ | RCT | 1 | 5/64 | 9/62 | Not applicable | 0.50 (0.16, 1.58) | 0.24 |
| — | LCM vs. placebo | RCT | 2 | 63/643 | 11/260 | P = 0.37; I 2 = 0% | 2.04 (1.08, 3.85) | 0.03 |
| Vertigo | LCM vs. PGB | Cohort study | 1 | 0/160 | 6/135 | Not applicable | 0.06 (0.00, 1.14) | 0.06 |
| — | LCM vs. placebo | RCT | 1 | 21/322 | 3/163 | Not applicable | 3.54 (1.07, 11.71) | 0.04 |
| — | — | Cohort study | 1 | 3/158 | 0/179 | Not applicable | 3.51 (0.18, 67.58) | 0.41 |
| Anxiety | LCM vs. TPM | Cohort study | 1 | 0/160 | 7/135 | Not applicable | 0.06 (0.00, 0.98) | 0.05 |
| — | LCM vs. ZNS | Cohort study | 1 | 0/160 | 7/141 | Not applicable | 0.06 (0.00, 1.02) | 0.05 |
| — | LCM vs. PGB | Cohort study | 1 | 0/160 | 4/135 | Not applicable | 0.09 (0.01, 1.73) | 0.11 |
| — | LCM vs. CBZ | RCT | 1 | 2/64 | 4/62 | Not applicable | 0.47 (0.08, 2.65) | 0.39 |
| Vision blurred | LCM vs. placebo | RCT | 2 | 75/622 | 8/201 | P = 0.37; I 2 = 0% | 2.89 (1.42, 5.89) | 0.004 |
| — | — | Cohort study | 1 | 8/358 | 0/179 | Not applicable | 8.52 (0.49, 146.85) | 0.14 |
| Insomnia | LCM vs. CBZ | RCT | 1 | 1/64 | 2/62 | Not applicable | 0.48 (0.04, 5.39) | 0.55 |
| Depression | LCM vs. CBZ | RCT | 1 | 3/64 | 0/62 | Not applicable | 7.11 (0.36, 140.62) | 0.20 |
| Digestive system | ||||||||
| Nausea/vomiting | LCM vs. TPM | Cohort study | 1 | 6/160 | 0/135 | Not applicable | 10.98 (0.62, 193.17) | 0.10 |
| — | LCM vs. ZNS | Cohort study | 1 | 6/160 | 13/141 | Not applicable | 0.41 (0.16, 1.04) | 0.06 |
| — | LCM vs. LEV | Cohort study | 1 | 6/160 | 0/136 | Not applicable | 11.06 (0.63, 194.60) | 0.10 |
| — | LCM vs. PGB | Cohort study | 1 | 6/160 | 3/135 | Not applicable | 1.69 (0.43, 6.62) | 0.45 |
| — | LCM vs. PER | Cohort study | 1 | 3/70 | 0/70 | Not applicable | 7.00 (0.37, 133.06) | 0.20 |
| — | LCM vs. CBZ | RCT | 1 | 10/64 | 10/62 | Not applicable | 0.96 (0.37, 2.50) | 0.94 |
| — | LCM vs. placebo | RCT | 3 | 203/944 | 25/364 | P = 0.33; I 2 = 10% | 2.82 (1.85, 4.28) | <0.001 |
| — | — | Cohort study | 1 | 5/358 | 0/179 | Not applicable | 5.52 (0.31, 99.19) | 0.25 |
| Abdominal pain | LCM vs. ZNS | Cohort study | 1 | 0/160 | 4/141 | Not applicable | 0.10 (0.01, 1.80) | 0.12 |
| Circulatory system | ||||||||
| Palpitation | LCM vs. placebo | Cohort study | 1 | 5/358 | 0/179 | Not applicable | 5.52 (0.31, 99.19) | 0.25 |
| Respiratory system | ||||||||
| Nasopharyngitis | LCM vs. CBZ | RCT | 1 | 8/64 | 6/62 | Not applicable | 1.33 (0.43, 4.09) | 0.62 |
| — | LCM vs. placebo | RCT | 2 | 70/685 | 29/347 | P = 0.59; I 2 = 0% | 1.21 (0.81, 1.83) | 0.35 |
| Upper respiratory tract infection | LCM vs. placebo | RCT | 2 | 56/684 | 22/281 | P = 0.53; I 2 = 0% | 0.98 (0.61, 1.57) | 0.94 |
| Locomotor system | ||||||||
| Tremor | LCM vs. TPM | Cohort study | 1 | 4/160 | 3/135 | Not applicable | 1.13 (0.26, 4.94) | 0.88 |
| — | LCM vs. ZNS | Cohort study | 1 | 4/160 | 0/141 | Not applicable | 7.94 (0.43, 146.15) | 0.16 |
| — | LCM vs. LEV | Cohort study | 1 | 4/160 | 0/136 | Not applicable | 7.66 (0.42, 140.98) | 0.17 |
| — | LCM vs. PGB | Cohort study | 1 | 4/160 | 0/135 | Not applicable | 7.60 (0.41, 139.95) | 0.17 |
| — | LCM vs. CBZ | RCT | 1 | 2/64 | 6/62 | Not applicable | 0.30 (0.06, 1.55) | 0.15 |
| — | LCM vs. placebo | RCT | 1 | 33/301 | 8/104 | Not applicable | 1.43 (0.68, 2.99) | 0.35 |
| Falls | LCM vs. PER | Cohort study | 1 | 1/70 | 1/70 | Not applicable | 1.00 (0.06, 15.67) | 1 |
| Skin system | ||||||||
| Irritability | LCM vs. TPM | Cohort study | 1 | 0/160 | 9/135 | Not applicable | 0.04 (0.00, 0.76) | 0.03 |
| — | LCM vs. PER | Cohort study | 1 | 0/70 | 3/70 | Not applicable | 0.14 (0.01, 2.72) | 0.20 |
| Rash | LCM vs. TPM | Cohort study | 1 | 4/160 | 0/135 | Not applicable | 7.60 (0.41, 139.95) | 0.17 |
| — | LCM vs. ZNS | Cohort study | 1 | 4/160 | 6/141 | Not applicable | 0.59 (0.17, 2.04) | 0.40 |
| — | LCM vs. LEV | Cohort study | 1 | 4/160 | 0/136 | Not applicable | 7.66 (0.42, 140.98) | 0.17 |
| — | LCM vs. PGB | Cohort study | 1 | 4/160 | 0/135 | Not applicable | 7.60 (0.41, 139.95) | 0.17 |
| Other systems | ||||||||
| Weight loss | LCM vs. TPM | Cohort study | 1 | 0/160 | 12/135 | Not applicable | 0.03 (0.00, 0.57) | 0.02 |
| — | LCM vs. ZNS | Cohort study | 1 | 0/160 | 6/141 | Not applicable | 0.07 (0.00, 1.19) | 0.07 |
| Any AEs | LCM vs. TPM | Cohort study | 1 | 36/160 | 42/135 | Not applicable | 0.72 (0.49, 1.06) | 0.10 |
| — | LCM vs. ZNS | Cohort study | 2 | 55/231 | 70/180 | P = 0.12; I 2 = 58% | 0.67 (0.39, 1.15) | 0.15 |
| — | LCM vs. LEV | Cohort study | 2 | 38/182 | 49/160 | P = 0.92; I 2 = 0% | 0.67 (0.46, 0.96) | 0.03 |
| — | LCM vs. PGB | Cohort study | 1 | 36/160 | 68/135 | Not applicable | 0.45 (0.32, 0.62) | <0.001 |
| — | LCM vs. PER | Cohort study | 1 | 32/70 | 51/70 | Not applicable | 0.63 (0.47, 0.84) | 0.002 |
| — | LCM vs. CBZ | RCT | 1 | 52/64 | 56/62 | Not applicable | 0.46 (0.16, 1.33) | 0.15 |
| — | LCM vs. placebo | RCT | 2 | 532/684 | 196/281 | P = 0.11; I 2 = 60% | 1.11 (0.96, 1.28) | 0.15 |
| — | — | Cohort study | 1 | 111/358 | 35/179 | Not applicable | 1.59 (1.13, 2.22) | 0.007 |
ASMs, antiseizure medications; LCM, lacosamide; TPM, topiramate; ZNS, zonisamide; LEV, levetiracetam; PGB, pregabalin; PER, perampanel; CBZ, carbamazepine; RCT, randomized clinical trial; N1, lacosamide group; N2, control group.