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.
To assess the efficacy and tolerability of melatonin as add-on treatment for epilepsy.
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 In addition, we contacted melatonin manufacturers (i.e. Nathura) and original investigators to identify any unpublished studies.
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.
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.
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.
Plain language summary
The use of melatonin as an adjunctive treatment for epilepsy
Epilepsy is one of the most common long-term disorders of the nervous system, and despite several antiepileptic drugs being available, 30% of people continue having seizures (fits). Reports have suggested that melatonin can work in epilepsy with a good safety profile. Melatonin is produced by the body and is prescribed by doctors to treat sleep disorders and problems such as jet lag.
We searched medical databases for clinical trials of melatonin added to another antiepileptic drug (add-on treatment) compared with antiepileptic drug plus add-on pretend treatment (placebo) or add-on no treatment in people with epilepsy. The participants were of any age or sex and included children and adults with disabilities. The studies measured reduction of seizure frequency by half, proportion of people with no seizures (seizure freedom), side effects, and improvement in quality of life.
We found six trials representing 125 participants for the present review. They reported two different comparisons: melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg.
Included trials did not evaluate seizure frequency, seizure freedom, and adverse events in a methodical way. Only one study reported seizure frequency and none of the participants had a change in frequency occurring during the trial compared to before the trial. Only one trial evaluated the effect of melatonin on quality of life and found no improvement with add-on melatonin compared with add-on placebo.
Quality of the evidence
The included trials were of poor methodological quality and it was not possible to draw any definitive conclusions about the role of melatonin in reducing seizure frequency or improving the quality of life in people with epilepsy.
The evidence was current to January 2016.