Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: A randomized controlled trial.
Study Goal
The researchers aimed to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizures in adults, focusing on seizure frequency, severity, sleep quality, and biochemical markers.
Results Summary
Add-on melatonin significantly improved responder rates, seizure-free rates, seizure frequency, seizure severity (NHS3), sleep quality (PSQI), and reduced serum neuron-specific enolase (NSE) compared to placebo. No significant differences were observed in Epworth sleepiness scale (ESS) or quality of life scoring.
Population
Adults with generalized epilepsy and generalized onset motor seizures (mean age 27.6 years, 80.8% male).
Effective Dosage
3 mg/day melatonin (add-on to valproate 20 mg/kg in two divided doses).
Duration
8 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
add-on melatonin with valproate | increase | responder rate | adults with generalized epilepsy with generalized onset motor seizure | - | significantly higher | #1 |
add-on melatonin with valproate | increase | seizure-free rate | adults with generalized epilepsy with generalized onset motor seizure | - | significantly higher | #2 |
add-on melatonin with valproate | decrease | frequency of seizures | adults with generalized epilepsy with generalized onset motor seizure | - | significantly higher reduction | #3 |
add-on melatonin with valproate | decrease | Chalfont-National Hospital seizure severity scale (NHS3) | adults with generalized epilepsy with generalized onset motor seizure | -2.39; 95%CI: -4.56 to -0.21 | significantly higher reduction | #4 |
add-on melatonin with valproate | decrease | Pittsburgh sleep quality index (PSQI) | adults with generalized epilepsy with generalized onset motor seizure | -1.40; 95%CI: -2.64 to -0.15 | improvement was significantly better | #5 |
add-on melatonin with valproate | no change | Epworth sleepiness scale (ESS) | adults with generalized epilepsy with generalized onset motor seizure | - | no significant difference in the change | #6 |
add-on melatonin with valproate | no change | quality of life in epilepsy inventory | adults with generalized epilepsy with generalized onset motor seizure | - | no significant difference in the change | #7 |
add-on melatonin with valproate | decrease | serum neuron-specific enolase (NSE) | adults with generalized epilepsy with generalized onset motor seizure | -2.01; 95% CI: -3.74 to -0.27 | decrease was significantly higher | #8 |
add-on melatonin | increase | serum glutathione reductase | adults with generalized epilepsy with generalized onset motor seizure | - | increased significantly | #9 |
add-on melatonin with valproate | no change | serum glutathione reductase | adults with generalized epilepsy with generalized onset motor seizure | - | no significant difference between the groups | #10 |
Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.