Table 4.
Summary of the studies about augmentation with antiepileptic drugs in TRD.
| Reference | n | Age Mean (SD), y | Design | Augmentation Molecule | Dosage | AD | Duration | Primary Outcome Measures | Results |
|---|---|---|---|---|---|---|---|---|---|
| RCTs | |||||||||
| Barbosa et al. [81] | 15 | 30.2 (±8.4) | Double-blind | Lamotrigine | Max: 100 mg/d | Fluoxetine | 6 weeks | HAM-D MADRS CGI | ↓ HAM-D: LAM = pcb (p = 0.21) ↓ MADRS: LAM = pcb (p = 0.46) ↓ CGI: LAM > pcb (p = 0.03) |
| Santos et al. [82] | 27 | 38.2 (±8.7) | Double-blind | Lamotrigine | Max: 200 mg/d | Various ADs | 8 weeks | CGI MADRS | ↓ CGI: LAM = pcb (p = 0.45) ↓ MADRS: LAM = pcb (p = 0.45; p-adj = 0.88) Response rates: LAM = pcb (p = 0.60) |
| Shapira et al. [86] | 20 | 47.5 (±14.1) | Double-blind | Phenytoin | N.A. | Fluvoxamine, fluoxetine, paroxetine | 4 weeks | HAM-D | ↓ HAM-D: PHE = pcb (p = 0.30) |
| Mowla and Kardeh [89] | 42 | 36.2 | Double-blind | Topiramate | Range: 100–200 mg/d Mean: 173.15 mg/d | Fluoxetine, citalopram, sertraline | 8 weeks | HAM-D CGI | ↓ HAM-D TOP: p < 0.001 ↓ HAM-D and ↓ CGI: TOP > pcb (p < 0.001) |
| Fang et al. [91] | 193 | Range: 18–65 | Head-to-head Multicenter, double-blind Comparison RIS/VAL/BUS/TRZ/T3 | Valproate | RIS: 2 mg/d VAL: 600 mg/d BUS: 30 mg/d TRZ: 100 mg/d T3: 80 mg/d | Paroxetine | 8 weeks | Remission at HAM-D | Remission rates: overall 37.3% RIS: 26.7% VAL: 48.7% BUS: 32.6% TRZ: 42.6% T3: 37.5% RIS = VAL = BUS = TRZ = T3 (p = 0.25) |
| Open studies | |||||||||
| Barbee and Jamhour [83] | 31 | 50.2 (±11.2) | Retrospective | Lamotrigine | Mean: 112.9 mg/d | Various ADs | Mean 41.8 weeks (at least 6 weeks) | CGI | (Very) much improved: 48.4% Mildly improved: 22.6% Unchanged: 29.0% |
| Gutierrez et al. [85] | 34 | 48.0 (±7.4) | Retrospective | Lamotrigine | Mean: 113.3 mg/d | Various ADs | 1 year | Medication Visit by MD | ↓ scores in target symptoms: - cognitive impairment, depressed mood, irritability, loss of interest (p < 0.01) energy (p < 0.001) sleep disturbance (p > 0.05) |
| Rocha and Hara [84] | 25 | Range: 18–65 | Retrospective | Lamotrigine | Mean (SD): 155.0 (±64.5) mg/d | Various ADs | 4 weeks | CGI | Response rate: 76% |
| Karaiskos et al. [87] | 20 | 72.6 (±6.3) | Open-label | Pregabalin | Mean (SD): 106.0 (±78.0) mg/d | Various ADs | 12 weeks | HAM-D HAM-A |
↓ HAM-D: p < 0.01 ↓ HAM-A: p < 0.05 |
| Ghabrash et al. [88] 2015 | 14 | Range: 19–59 | Comparison of psychometric scores at T0 (pre-treatment) with scores at: T1 (1 month) T4 (4 months) T7 (7 months) | Valproate | 375–1000 mg/d | Various ADs | 7 months | MADRS CGI |
↓ MADRS: T0 vs. T1 (p < 0.001) T4 (p < 0.001) T7 (p < 0.001) ↓ CGI: T0 vs. T1 (p = 0.03) T4 (p < 0.001) T7 (p < 0.001) |
| Fornaro et al. [90] | 24 | 50.7 (±0.2) | Open-label | Zonisamide | 75 mg/d | Duloxetine | 12 weeks | HAM-D | Response rate: 58.3% |
Key: AD = antidepressant; BUS = buspirone; CGI = Clinical Global Impression; GAF = Global Assessment of Functioning; HAM-A = Hamilton Anxiety Rating Scale; HAM-D = Hamilton Depression Rating Scale; LAM = lamotrigine; MADRS = Montgomery–Åsberg Depression Rating Scale; MD = medical doctor; pcb = placebo; PHE = phenytoin; RCT = randomized controlled trial; RIS = risperidone; SD = standard deviation; SSRI = Selective Serotonin Reuptake Inhibitor; TOP = topiramate; TRZ = trazodone; VAL = valproate.