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. 2016 Aug 11;2016(8):CD006967.
doi: 10.1002/14651858.CD006967.pub4.

Melatonin as add-on treatment for epilepsy

Francesco Brigo  1 , Stanley C Igwe, Alessandra Del Felice
Affiliations

Melatonin as add-on treatment for epilepsy

Francesco Brigo et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the original Cochrane review published in Issue 6, 2012.Epilepsy is one of the most common chronic neurological disorders. Despite the plethora of antiepileptic drugs (AEDs) currently available, 30% of people continue having seizures. This group of people requires a more aggressive treatment, since monotherapy, the first choice scheme, fails to control seizures. Nevertheless, polytherapy often results in a number of unwanted effects, including neurological disturbances (somnolence, ataxia, dizziness), psychiatric and behavioural symptoms, and metabolic alteration (osteoporosis, inducement or inhibition of hepatic enzymes, etc.). The need for better tolerated AEDs is even more urgent in this group of people. Reports have suggested an antiepileptic role of melatonin with a good safety profile.

Objectives: To assess the efficacy and tolerability of melatonin as add-on treatment for epilepsy.

Search methods: For the latest update, we searched the Cochrane Epilepsy Group's Specialized Register (12 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 12 January 2016), and MEDLINE (Ovid, 11 January 2016). We searched the bibliographies of any identified study for further references. We handsearched selected journals and conference proceedings. We applied no language restrictions. In addition, we contacted melatonin manufacturers (i.e. Nathura) and original investigators to identify any unpublished studies.

Selection criteria: Randomized controlled trials; double, single, or unblinded trials; parallel group or cross-over studies. People with epilepsy regardless of age and gender, including children and adults with disabilities. Administration of melatonin as add-on treatment to any AED(s) compared to add-on placebo or no add-on treatment.

Data collection and analysis: Review authors independently selected trials for inclusion according to pre-defined criteria, extracted relevant data, and evaluated the methodological quality of trials. We assessed the following outcomes: at least 50% seizure reduction, seizure freedom, adverse events, and quality of life.

Main results: We included six publications, with 125 participants (106 aged under 18 years). Two different comparisons were available: melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg. Despite our primary intention, due to insufficient information on outcomes, we were unable to perform any meta-analyses, but summarized data narratively. Four studies were randomized, double-blind, cross-over, placebo-controlled trials and two were randomized, double-blind, parallel, placebo-controlled trials. Only two studies provided the exact number of seizures during the trial compared to the baseline: none of the participants with seizures during the trial had a change in seizure frequency compared with the baseline. Two studies systematically evaluated adverse effects (worsening of headache was reported in a child with migraine under melatonin treatment). Only one study systematically evaluated quality of life, showing no statistically significant improvement in quality of life in the add-on melatonin group.

Authors' conclusions: Included studies were of poor methodological quality, and did not systematically evaluate seizure frequency and adverse events, so that it was impossible to summarize data in a meta-analysis. It is not possible to draw any conclusion about the role of melatonin in reducing seizure frequency or improving quality of life in people with epilepsy.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram. This diagram refers only to the updated version of the review.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Coppola 2004 {published data only}
    1. Coppola G, Iervolino G, Mastrosimone M, Torre G, Ruiu F, Pascotto A. Melatonin in wake‐sleep disorders in children, adolescents and young adults with mental retardation with or without epilepsy: a double‐blind, cross‐over, placebo‐controlled trial. Brain Development 2004;26(6):373‐6. - PubMed
Goldberg‐Stern 2012 {published data only}
    1. Goldberg‐Stern H, Oren H, Peled N, Garty BZ. Effect of melatonin on seizure frequency in intractable epilepsy: a pilot study. Journal of Child Neurology 2012;27(12):1524‐8. - PubMed
    1. Goldberg‐Stern H, Oren H, Shuper A, Peled N, Garty BZ. Melatonin in intractable epilepsy: a possible positive effect. Epilepsia 2010;51(Suppl 4):100.
Gupta 2004a {published data only}
    1. Gupta M, Gupta YK, Aneja AS, Kohli K. Effects of add‐on melatonin on sleep in epileptic children on carbamazepine monotherapy: a randomized placebo controlled trial. Sleep and Biological Rhythms 2004;2:215‐9.
Gupta 2004b {published data only}
    1. Gupta M, Aneja S, Kohli K. Add‐on melatonin improves quality of life in epileptic children on valproate monotherapy: a randomized, double‐blind, placebo‐controlled trial. Epilepsy & Behavior 2004;5:316‐21. - PubMed
Hancock 2005 {published data only}
    1. Hancock E, O'Callaghan F, Osborne JP. Effect of melatonin dosage on sleep disorder in tuberous sclerosis complex. Journal of Child Neurology 2005;20(1):78‐80. - PubMed
Jain 2015 {published data only}
    1. Jain S, Horn P, Simakajornboon N, Holland K, Glauser T. Melatonin improves sleep in children with epilepsy: results from a randomized, double‐blind, placebo‐controlled, cross‐over study. Epilepsy Currents 2014;14(Suppl 1):442.
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References to other published versions of this review

Brigo 2008
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