Evidence table for systematic reviews
Study reference Design Inclusion Criteria Quality Results Comments

Tjia- Leong, 2010

Systematic review (Cochrane)

-randomized double, single and unblinded controlled trials

-placebo or actively controlled

-parallel group or cross-over studies

-any age with drug -resistent primary generalized epilepsy

-intervention group received lamotrigine in addition to conventional AED treatment

 

Exlusion criteria:

-participants with absence epilepsy and Lennox Gastaut syndrome

 

Search: adequate

 

Selection: adequate

 

Quality assessment of individual studies:

Yes, according to Jadad validated quality scale

-2 small trials (Beran 1998, Biton 2005) both unclear allocation concealment and no description of method of double-blinding

 

-Beran: 7 of 14 patients had 50% or greater reduction in seizure frequency in comparison to placebo (P=0.03)

-Biton: 37 of 58 patients (64%) in intervention group had 50% or greater reduction in seizure frequency in comparison to 23 of 59 patients (39%) in placebo group  (P<0.05), RR 1.64 (95% CI 1.13 to 2.38)

 

-Most common adverse events:

Beran: ataxia (12%), dizziness (8%) and somnolence (8%) with lamotrigine. No effects using placebo

Biton: dizziness (5%), somnolence (5%) and nausea (3%) respectively 2%, 2% and 3% in placebo group

Colleran et al., 2017

SR and meta-analysis of RCTs

All vivo studies, all drug resistant patients of any gender or ethnic background. Patients included required a confirmed diagnosis of IGE in accordance with

ILAE classification (1989). All studies included were RCTs of AED’s compared with each other or placebo and had baseline seizure data recorded only.

Search: adequate

Selection: adequate

Quality assessment of individual studies: GRADE not reported

Outcome measure-1

Defined as patients with >50% reduction in seizures

Effect measure: RR [95% CI]:

A: 1.60 [1.22, 2.10]

B: NR

C: 2.82 [1.43, 5.56]

D: 1.47 [1.09, 2.00]

E: 2.27 [1.57, 3.28]

F: NR

G: 1.63 [1.19, 2.23]

H: 2.50 [1.51, 4.15]

I: NR

Pooled effect (random effects model):

1.82 [95% CI 1.51 to 2.20] favoring intervention group

Heterogeneity (I2): 36%

Outcome measure-2

Defined as seizure freedom

Effect measure: RR [95% CI]:

A: 3.15 [1.58, 6.28]

B: no control data was provided

C: 2.56 [0.53, 12.44]

D: 1.22 [0.57, 2.60]

E: 3.34 [1.78, 6.26]

F: NR

G: 2.27 [1.20, 4.30]

H: 5.00 [1.53, 16.38]

I: 2.86 [1.05, 7.77]

Pooled effect (random effects model):

2.59 [95% CI 1.90 to 3.51] favoring intervention group

Heterogeneity (I2): 2%

Outcome measure-3

Defined as adverse effects, n (%)

A: patients withdrew due to adverse effects I: 1 (1.3%)/ C: 4 (4.8%).

Nasopharyngitis: 13.9% (n = 11) , headache 10.1% (n = 8), fatigue 10.1% (n = 8), dizziness 7.6% (n = 6), diarrhoea 7.6% (n = 6) and somnolence 6.3% (n = 5)

Serious adverse effects resulting in hospitalization or disability: I: 3 (3.8%)/ C: 8 (9.5%)

C: seasonal illness

including upper respiratory tract infection 41% (n = 16).

Central nervous system (CNS) side effects included somnolence 26% (n = 10), fatigue 18% (n = 7), difficulty with memory 13% (n = 5)

and headache 13% (n = 5). Some CNS adverse events were reported more frequent in the topiramate group than the placebo group; somnolence, anorexia, difficulty with memory, nervousness, psychomotor slowing, fatigue and speech disorders and speech related problems. However, in the placebo group, headache dizziness, insomnia and personality disorder are reported more frequently.

D/ E/ I:

Lamotrigine was well tolerated.

D: I: 13 (22%)/ C: 6 (10%)

5% experienced dizziness (n = 3), 5% somnolence (n = 3), and 5% had nausea (n = 3) in the lamotrigine treatment group [21]. In contrast, 2% (n = 1), 2% (n = 1) and 3% (n = 2) of patients in the placebo group

experienced these side effects respectively

E: A total of 5% (n = 3)

in the lamotrigine group and 2% (n = 1) in placebo group

prematurely withdrew at the doubleblind phase due to adverse effects. Dizziness was also experienced by 6% (n = 4) of patients

G: TEAE I: 67, (82.7%) / C: 59 (72%). The most common adverse effects of treatment with perampanel reported (>10%) was dizziness, fatigue, headache, somnolence and irritability.

H: headache: I: 13 (21.6%), depression: n=3, nervousness n=2

Author’s conclusion

This systematic review demonstrated efficacy of adjunctive anti-epileptic drugs with regard to 50% reduction and seizure freedom. Adverse events are identified in all of the studies in the drug treatment groups but are consistent with previous studies of these drugs. Additional adequately powered studies with long term follow up needs to be conducted to unequivocally establish the long term efficacy and tolerability of anti-epileptic drug’s for patients with drug resistant idiopathic generalised epilepsy