Ramelteon can relieve the symptoms of refractory chronic migraine with insomnia

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Ramelteon can relieve the symptoms of refractory chronic migraine with insomnia

Ramelteon is a selective melatonin receptor agonist and exerts beneficial effects in the treament of insomnia. For significant improvement of migraine, the efficacy of ramelteon has been explained in this case report. Most likely, the possible mechanism for the ramelteon in the migraine relief might be associated with itsmelatonin effect.

This is a case of a 71 years old female patient who suffered from chronic migraine for 2 decades. After 2 weeks of  treatment with ramelteon (8 mg/day), her sleep duration was reported to be prolonged to 4–5 hours with less fragmentation. In addition, her migraine severity started to dimnish (MIDAS scores, 11). After 6 months of ramelteon (8 mg/day) treatment, the migraine severity continued to mitigate (MIDAS scores, 6) with constant sleeping quality (ISI score, 14).

Thus, significant improvements in migraine severity and insomnia after the use of ramelteon was experienced by the patient. It was speculated that ramelteon have significant effect in migraine and helps prolong the sleep duration. This effect may be associated with melatonin, which might ease the headache via the different possible mechanisms. These mechanisms may include an anti-inflammatory effect, free radical scavenging, reduction of pro-inflammatory cytokine, membrane stabilization, nitric oxide synthase activity and dopamine release inhibition, GABA and opioid analgesia potentitation, glutamate neurotoxicity protection, neurovascular regulation, cytoprotection and antiallodynic action. The analgesic effect could be due to the pineal gland, the primary source of serotonin and melatonin. The modulation of melatonin receptor might be a better option for the analgesic effects as the clinical trial of melatonin administration showed no significant improvements in migraine severity. The pain sensation can also be relieved via the modulation of serotonin system by the ramelteon. Also, the chemical structure of ramelteon was similar to that of indomethacin, which is a type of non-steroidal anti-inflammatory drug. In one of the animal model study, the antinociceptive and antiallodynic actions of melatonin were perceived in different kinds of pathways, like intrathecally or intracerebroventricular routes. The use of ramelteon, a type of MT1 and MT2 agonist, could also relieve the pain, and also there are no free radical scavenger consequences. The state-of-art treatment of refractory chronic migraine also inculcates the ramelteon due to selective M1 receptor agonism. We can consider the use of ramelteon for refractory chronic migraine with insomnia from the successful experience in this case.


Clin Psychopharmacol Neurosci. 2016 Nov; 14(4): 405–406.

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Original title of article:

The Relief Effects of Ramelteon on Refractory Chronic Migraine: A Case Report


Sahana Shetty et al.

Clin Psychopharmacol Neurosci. 2016 Nov; 14(4): 405–406.
Ramelteon can relieve the symptoms of refractory chronic migraine with insomnia
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