Melatonin vs. Clobazam for Preventing Recurrent Simple Febrile Seizures: A Randomized Clinical Trial
Abstract
Febrile seizures are the most common neurologic disorder in infants and young children. Febrile seizures generally have a good prognosis, but approximately one-third of patients may experience a second attack. This study was conducted to assess the effectiveness of melatonin in preventing the recurrence of subsequent seizures. In this prospective randomized clinical trial study, 60 children with febrile seizures were enrolled in two groups of 30. Clobazam was administered to the control group, while melatonin was given to the intervention group for prophylaxis. Over a 12-month telephone follow-up, the number of febrile illnesses and seizure attacks, as well as drug side effects, was recorded of the 60 children included in this study, 56.7% were boys. The mean age of the participants was 30.22±11.69 months. Seven patients experienced febrile seizures after receiving prophylactic medication, including three patients in the melatonin group and four in the clobazam group. This difference was not statistically significant (P=1.00). Additionally, only two patients in the control group experienced sleepiness. Melatonin may be effective in preventing recurrent febrile seizure episodes without any serious side effects. Iranian Registry of Clinical Trial (IRCT20221102056380N1).
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8. Salehiomran M, Hoseini SM, Ghabeli Juibary A. Intermittent Diazepam versus Continuous Phenobarbital to Prevent Recurrence of Febrile Seizures: A Randomized Controlled Trial. Iran J Child Neurol. 2016 Winter;10(1):21-4. PMID: 27057183; PMCID: PMC4815482.
9. Khosroshahi N, Faramarzi F, Salamati P, Haghighi SM, Kamrani K. Diazepam versus clobazam for intermittent prophylaxis of febrile seizures. Indian J Pediatr. 2011 Jan;78(1):38-40. doi: 10.1007/s12098-010-0220-0
10. Smith DK, Sadler KP, Benedum M. Febrile Seizures: Risks, Evaluation, and Prognosis. Am Fam Physician. 2019 Apr 1;99(7):445-450. PMID: 30932454.
11. Karynna A A, Rocha A, Cipolla-Neto J, Amado D. Epilepsy: Neuroprotective, Anti-inflammatory, and Anticonvulsant effects of Melatonin. In: Lore Correia and Germaine Mayers, Melatonin: Medical Uses and Role in Health and Disease. 2018 Nova Science Publishers, 233-253.
12. Zakharov AV, Khivintseva EV, Pytin VF, Sergeeva MS, Antipov OI. Melatonin - izvestnye i novye oblasti klinicheskogo primeneniia [Melatonin - known problems and perspectives of clinical usage]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4. Vyp. 2):74-78. Russian. doi: 10.17116/jnevro20171174274-78
13. Barghout MS, Al-Shahawy AK, El Amrousy DM, Darwish AH. Comparison Between Efficacy of Melatonin and Diazepam for Prevention of Recurrent Simple Febrile Seizures: A Randomized Clinical Trial. Pediatr Neurol. 2019 Dec;101:33-38. doi: 10.1016/j.pediatrneurol.2019.01.010
14. Assawabumrungkul S, Chittathanasesh V, Fangsaad T. Efficacy of melatonin for febrile seizure prevention: A clinical trial study. Neuroscience Informatics. 2022;2(3):100089. doi.org/10.1016/j.neuri.2022.100089
15. Bajaj AS, Bajaj BK, Puri V, Tayal G. Intermittent clobazam in febrile seizures: an Indian experience. Journal of Pediatric Neurology. 2005;3(1):19-23.
16. Ghazavi A, Abbasi E, Nikibakhsh A, Sadeghi E, Sadeghimanesh J. Comparison of prophylactic effect of clobazam and diazepam in children with simple febrile convulsion (SFC). International Journal of Tropical Medicine. 2016;11(2):21-3.
17. Rosman NP, Colton T, Labazzo J, Gilbert PL, Gardella NB, Kaye EM, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med. 1993 Jul 8;329(2):79-84. doi: 10.1056/NEJM199307083290202.
18. Rose W, Kirubakaran C, Scott JX. Intermittent clobazam therapy in febrile seizures. Indian J Pediatr. 2005 Jan;72(1):31-3. doi: 10.1007/BF02760577
19. Kumar V, Gupta A. Intermittent clobazam prophylaxis in simple febrile convulsions: a randomised controlled trial. International Journal of Contemporary Pediatrics; 2019.6(2). doi: https://doi.org/10.18203/2349-3291.ijcp20190720
20. Sattar S, Saha SK, Parveen F, Banu LA, Momen A, Ahmed AU, et al. Intermittent prophylaxis of recurrent febrile seizures with clobazam versus diazepam. Mymensingh Med J. 2014 Oct;23(4):676-85.
21. Verma N, Maiti R, Mishra BR, Jha M, Jena M, Mishra A. 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. J Neurosci Res. 2021 Jun;99(6):1618-1631. doi: 10.1002/jnr.24820.
2. Natsume J, Hamano SI, Iyoda K, Kanemura H, Kubota M, Mimaki M, et al. New guidelines for management of febrile seizures in Japan. Brain Dev. 2017 Jan;39(1):2-9. doi: 10.1016/j.braindev.2016.06.003.
3. Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015 Aug;56(8):1185-97. doi: 10.1111/epi.13057.
4. Hesdorffer DC, Benn EK, Bagiella E, Nordli D, Pellock J, Hinton V, et al. Distribution of febrile seizure duration and associations with development. Ann Neurol. 2011 Jul;70(1):93-100. doi: 10.1002/ana.22368.
5. Patterson JL, Carapetian SA, Hageman JR, Kelley KR. Febrile seizures. Pediatr Ann. 2013 Dec;42(12):249-54. doi: 10.3928/00904481-20131122-09
6. Offringa M, Newton R, Nevitt SJ, Vraka K. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2021 Jun 16;6(6):CD003031. doi: 10.1002/14651858.CD003031.pub4
7. Verrotti A, Latini G, di Corcia G, Giannuzzi R, Salladini C, Trotta D, et al. Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence. Eur J Paediatr Neurol. 2004;8(3):131-4. doi: 10.1016/j.ejpn.2004.01.008.
8. Salehiomran M, Hoseini SM, Ghabeli Juibary A. Intermittent Diazepam versus Continuous Phenobarbital to Prevent Recurrence of Febrile Seizures: A Randomized Controlled Trial. Iran J Child Neurol. 2016 Winter;10(1):21-4. PMID: 27057183; PMCID: PMC4815482.
9. Khosroshahi N, Faramarzi F, Salamati P, Haghighi SM, Kamrani K. Diazepam versus clobazam for intermittent prophylaxis of febrile seizures. Indian J Pediatr. 2011 Jan;78(1):38-40. doi: 10.1007/s12098-010-0220-0
10. Smith DK, Sadler KP, Benedum M. Febrile Seizures: Risks, Evaluation, and Prognosis. Am Fam Physician. 2019 Apr 1;99(7):445-450. PMID: 30932454.
11. Karynna A A, Rocha A, Cipolla-Neto J, Amado D. Epilepsy: Neuroprotective, Anti-inflammatory, and Anticonvulsant effects of Melatonin. In: Lore Correia and Germaine Mayers, Melatonin: Medical Uses and Role in Health and Disease. 2018 Nova Science Publishers, 233-253.
12. Zakharov AV, Khivintseva EV, Pytin VF, Sergeeva MS, Antipov OI. Melatonin - izvestnye i novye oblasti klinicheskogo primeneniia [Melatonin - known problems and perspectives of clinical usage]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4. Vyp. 2):74-78. Russian. doi: 10.17116/jnevro20171174274-78
13. Barghout MS, Al-Shahawy AK, El Amrousy DM, Darwish AH. Comparison Between Efficacy of Melatonin and Diazepam for Prevention of Recurrent Simple Febrile Seizures: A Randomized Clinical Trial. Pediatr Neurol. 2019 Dec;101:33-38. doi: 10.1016/j.pediatrneurol.2019.01.010
14. Assawabumrungkul S, Chittathanasesh V, Fangsaad T. Efficacy of melatonin for febrile seizure prevention: A clinical trial study. Neuroscience Informatics. 2022;2(3):100089. doi.org/10.1016/j.neuri.2022.100089
15. Bajaj AS, Bajaj BK, Puri V, Tayal G. Intermittent clobazam in febrile seizures: an Indian experience. Journal of Pediatric Neurology. 2005;3(1):19-23.
16. Ghazavi A, Abbasi E, Nikibakhsh A, Sadeghi E, Sadeghimanesh J. Comparison of prophylactic effect of clobazam and diazepam in children with simple febrile convulsion (SFC). International Journal of Tropical Medicine. 2016;11(2):21-3.
17. Rosman NP, Colton T, Labazzo J, Gilbert PL, Gardella NB, Kaye EM, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med. 1993 Jul 8;329(2):79-84. doi: 10.1056/NEJM199307083290202.
18. Rose W, Kirubakaran C, Scott JX. Intermittent clobazam therapy in febrile seizures. Indian J Pediatr. 2005 Jan;72(1):31-3. doi: 10.1007/BF02760577
19. Kumar V, Gupta A. Intermittent clobazam prophylaxis in simple febrile convulsions: a randomised controlled trial. International Journal of Contemporary Pediatrics; 2019.6(2). doi: https://doi.org/10.18203/2349-3291.ijcp20190720
20. Sattar S, Saha SK, Parveen F, Banu LA, Momen A, Ahmed AU, et al. Intermittent prophylaxis of recurrent febrile seizures with clobazam versus diazepam. Mymensingh Med J. 2014 Oct;23(4):676-85.
21. Verma N, Maiti R, Mishra BR, Jha M, Jena M, Mishra A. 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. J Neurosci Res. 2021 Jun;99(6):1618-1631. doi: 10.1002/jnr.24820.
| Files | ||
| Issue | Articles in Press: Vol 64 No 03 (2026) | |
| Section | Original Articles | |
| Keywords | ||
| Febrile seizure Prophylaxis Melatonin Clobazam | ||
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How to Cite
1.
Khosroshahi N, Zare-Amanat S, Khayatzadeh-kakhki S, Eftekhari K. Melatonin vs. Clobazam for Preventing Recurrent Simple Febrile Seizures: A Randomized Clinical Trial. Acta Med Iran. 2026;.
