Management Idiopathic hypersomnia

1 management

1.1 stimulants
1.2 wakefulness promoting medications
1.3 sleep promoting medications
1.4 histamine-directed medications
1.5 gaba-directed medications

1.5.1 flumazenil
1.5.2 clarithromycin

management

currently, there no cure idiopathic hypersomnia. also, because underlying disease mechanism not yet understood (see causes), treatment efforts have focused on symptom management. although there several fda-approved medications use in narcolepsy, there no fda-approved medicines idiopathic hypersomnia. therefore, wake-promoting medications used in narcolepsy commonly used off-label manage excessive daytime sleepiness of idiopathic hypersomnia. these treatments have not been studied same extent in patients idiopathic hypersomnia, , patients idiopathic hypersomnia not achieve adequate control of symptoms these medications.

however, current research raising possibility of several other potential medication options idiopathic hypersomnia. brain systems regulating sleepiness , wakefulness better understood, scientists in better position design treatments target key portions of system. (see research)

in addition medications, behavioral approaches , sleep hygiene techniques recommended, although have little overall positive impact on disease. planned naps unhelpful, both long , unrefreshing. although behavioral approaches have not been shown improve eds, goal, in cbt (cognitive behavioral therapy), patients learn reduce negative emotional responses (e.g. frustration, anger, depression) disease symptoms. furthermore, because idiopathic hypersomnia may lead marriage breakdown, extensive counseling patient s partners, educating them symptomatology , treatment options, must part of comprehensive management plan... education of relatives, friends, , colleagues helps patient function better incurable disease.

although management of idiopathic hypersomnia not codified, recommended initial therapy conservative, focusing on behavioral modifications , medications such modafinil , atomoxetine. however, treatment may have more aggressive (high-dose stimulants, sodium oxybate, etc.) on case-by-case, empirical trial basis. cause , evolution unknown in these conditions, important challenge diagnosis , therapy on time.

overall, medications used idiopathic hypersomnia (all off-label) far satisfactory. cns stimulants tend less effective idiopathic hypersomnia narcolepsy , may less tolerated.

stimulants

there several stimulants approved fda treatment of excessive sleepiness due narcolepsy. these include methylphenidate (e.g., ritalin) , dextroamphetamine, among others. selegiline may useful, metabolic precursor of amphetamine , exerts of therapeutic effects through amphetamine metabolism. increased dopamine release felt main property explaining wake-promotion these medications. although stimulants can reduce sleepiness in short medium term, effective long-term, patients become resistant effects. in addition, there unpleasant potential side effects, include heart problems, aggressive behavior, , dependence. insomnia common side effect , may require additional treatment.

mazindol stimulant similar amphetamines has been shown effective in treating hypersomnia in narcoleptics. however, not approved in us.

caffeine 1 of safer nondopaminergic wake-promoting compounds. used has intolerable side effects @ high doses (including cardiovascular), , not efficient enough patients hypersomnia or narcolepsy.

wakefulness promoting medications

the non-stimulant wake-promoting medications approved use in narcolepsy include modafinil , armodafinil. pharmacology not understood, these medications appear influence brain chemistry increases wakefulness. elevate hypothalamic histamine levels, , known bind dopamine transporter, thereby inhibiting dopamine reuptake. modafinil can cause uncomfortable side effects, including nausea, headache, , dry mouth patients, while other patients report no noticeable improvement on relatively high dosages. may interact low-dose contraceptives, potentially reducing efficacy, although scientific data supporting claim weak , rests on poorly documented anecdotes. new histamine-directed wake-promoting medications under development (see histamine-directed medications).

atomoxetine (or reboxetine in europe) adrenergic reuptake inhibitor increases wakefulness (generally less medications act on dopamine) , has been argued have clear use in therapeutic arsenal against narcolepsy , hypersomnia although undocumented clinical trials.

ritanserin serotonin antagonist has been shown improve daytime alertness , subjective sleep quality in patients on usual narcolepsy medications. intended adjunct (supplement main therapeutic agent), , although not available in us, available in europe.

although anti-depressants, in general, have not been found helpful treatment of idiopathic hypersomnia, bupropion known have wake-promoting effects. low potency nonspecific monoamine reuptake inhibitor has dat [dopamine-reuptake] inhibitory effects.

sleep promoting medications

sleep promoting medications can ensuring effective sleep sleep @ appropriate time.

sodium oxybate orphan drug designed treatment of narcolepsy. has been shown promote deep sleep , improve daytime sleepiness (as cataplexy) in patients narcolepsy; however, effects in idiopathic hypersomnia not characterized. common side effects include nausea, dizziness, , hallucinations. 2016 study leu-semenescu et al. found sodium oxybate improved daytime sleepiness in idiopathic hypersomnia same degree in patients narcolepsy type 1, , drug improved severe sleep inertia in 71% of hypersomnia patients.

histamine-directed medications

based on role of histamine in keeping people awake (and hence common side effect of anti-histamines such diphenhydramine causing sleepiness), medications act on histamine under development treatment of excessive sleepiness. remains seen whether these h3 antagonists (i.e., compounds such pitolisant promote release of wake-promoting amine histamine) particularly useful wake-promoting agents in treatment of idiopathic hypersomnia.

gaba-directed medications

given possible role of hyperactive gabaa receptors in idiopathic hypersomnia, medications counteract activity being studied test potential improve sleepiness. these include clarithromycin , flumazenil.

flumazenil

flumazenil gabaa receptor antagonist on market of jan 2013, , manufactured intravenous formulation. approved fda use in anesthesia reversal , benzodiazepine overdose. however, given pharmacology, researchers consider promising medication in treatment of idiopathic hypersomnia. results of small, double-blind, randomized, controlled clinical trial published in november 2012. research showed flumazenil provides relief patients csf contains unknown somnogen enhances function of gabaa receptors, making them more susceptible sleep-inducing effect of gaba. 1 patient, daily administration of flumazenil sublingual lozenge , topical cream has proven effective several years. 2014 case report showed improvement in idiopathic hypersomnia symptoms after treatment continuous subcutaneous flumazenil infusion. supply of generic flumazenil thought low meet potential demand treatment of idiopathic hypersomnia. however, scarcity has eased, , dozens of patients being treated flumazenil off-label.

clarithromycin

in test tube model, clarithromycin (an antibiotic approved fda treatment of infections) found return function of gaba system normal in patients idiopathic hypersomnia. investigators therefore treated few patients off-label clarithromycin, , felt symptoms improved treatment. in order further determine whether clarithromycin beneficial treatment of idiopathic hypersomnia, small, double-blind, randomized, controlled clinical trial completed in 2012. in pilot study, clarithromycin improved subjective sleepiness in gaba-related hypersomnia. larger trials of longer duration warranted. in 2013, retrospective review evaluating longer-term clarithromycin use showed efficacy in large percentage of patients gaba-related hypersomnia. important note positive effect of clarithromycin secondary benzodiazepine antagonist-like effect, not antibiotic effects, , treatment must maintained.