Apparent resolution of hypersomnia episodes in two patients with Kleine–Levin syndrome following treatment with the melatonin receptor agonist ramelteon

Kleine–Levin syndrome (KLS) is a rare disorder characterized by episodic bouts of severe hypersomnia associated with cognitive and behavioral abnormalities and normal alertness and functioning in between episodes. The pathophysiology is unclear but may involve neurotransmitter abnormalities, hypothalamic/thalamic dysfunction, viral/autoimmune etiology, or circadian abnormalities. No single treatment has been shown to be reliably efficacious; lithium has demonstrated the most consistent efficacy, although many do not respond and its use is limited by side effects. Due to the evidence of circadian involvement, we hypothesized that strengthening circadian signals may ameliorate symptoms. Ramelteon is a potent melatonin receptor agonist. In this report, two patients with KLS are described with apparent resolution of hypersomnia episodes following ramelteon initiation.