Rare Neurology News
Narcolepsy is a chronic brain disorder that involves poor control of sleep-wake cycles. People with narcolepsy have episodes of extreme daytime sleepiness and sudden, irresistible bouts of sleep (called "sleep attacks") that can occur at any time, and may last from seconds or minutes
Age of Onset
Most cases of narcolepsy are sporadic, which means they occur in people with no history of the disorder in their families. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (parents, siblings, and children) of people with narcolepsy with cataplexy have a 40 times greater risk of developing the condition compared with people in the general population.
Narcolepsy is a disorder that disrupts sleep-wake processes. Its primary symptom is excessive daytime sleepiness (EDS), which occurs because the brain is unable to properly regulate wakefulness and sleep. The cause of narcolepsy isn't well understood but may involve genetic factors and abnormal signaling in the brain. Narcolepsy causes sudden attacks of sleep. Sudden loss of muscle tone and hallucinations might occur.†
5 Facts you should know
Type 1 narcolepsy is defined as narcolepsy with cataplexy; Type 2 is narcolepsy without cataplexy
The most typical symptoms are excessive daytime sleepiness, cataplexy, sleep paralysis, and hallucinations
About 70% of those affected experience episodes of a sudden loss of muscle strength, known as cataplexy
The loss of hypocretin-producing neurons in the hypothalamus is the primary cause of Type 1 narcolepsy
There is an increased prevalence of cardiovascular and cardiometabolic conditions, such as hypertension, obesity, diabetes, and hypercholesterolemia in patients with narcolepsy
Interest over time
Common signs & symptoms
Excessive daytime somnolence
Excessive daytime sleepiness
Transient global amnesia
Abnormal rapid eye movement sleep
Abnormality of vision
Abnormality of sight
Stimulants - Stimulants help keep you awake and alert
Amphetamine - Stronger stimulant for severe daytime sleepiness
Amphetamine and dextroamphetamine mix (Adderall)
Methylphenidate (Aptensio XR, Concerta, Ritalin)
The FDA has approved three GHB formulations for treating narcolepsy. Both contain sodium oxybate, a powerful medication that can be habit-forming.
Calcium, magnesium, potassium, and sodium oxybate (Xywav)
This newer medication can cause many of the same side effects as Xyrem. But it has 90% less salt than the older drug.
Sodium oxybate (Xyrem)
It may cause dizziness, an upset stomach, or make you wet the bed or sleepwalk. It’s also very high in salt. It may not be right for you if you have high blood pressure, kidney problems, or certain heart conditions.
Several different kinds can treat cataplexy. Some may help with the sleep paralysis and hallucinations around the time of sleep that narcolepsy can cause.
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
Tricyclic antidepressants (TCAs)
TCAs are older drugs that can cause dry mouth, lightheadedness, and constipation. SSRIs and SNRIs can cause weight gain, insomnia, and digestive problems.
Approved in 2019 to treat excessive daytime sleepiness. Unlike some other narcolepsy medications, it doesn’t keep birth control pills from working.
Selective Histamine 3 Receptor Antagonist/Inverse Agonist
This medication helps release more histamine, which encourages wakefulness.
Prescribed for daytime sleepiness. It also may prevent episodes.
Top Clinical Trials
|Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia||This study will evaluate which medication works better to improve sleepiness. The researchers will also see which medication is better for other symptoms including difficulty waking up and difficulty thinking, as well as seeing which medication causes fewer side. Finally, this study will see if any information about patients (such as age or sleep study features) predicts responding better to one medication or the other.||Phase 2||Recruiting||Drug: Modafinil|Drug: Amphetamine-Dextroamphetamine||More Info|
|Study to Evaluate the Abuse Liability, Pharmacokinetics, Safety and Tolerability of an Abuse-Deterrent d-Amphetamine Sulfate Immediate Release Formulation (ADAIR)||This is a randomized, double-blind, double-dummy, placebo- and active-controlled 4 period, 4 way crossover study to assess the intranasal abuse potential of manipulated ADAIR formulation in nondependent, recreational stimulant users. The study will consist of an outpatient Screening Visit, an in clinic Qualification Phase, an in-clinic Treatment Phase, and an outpatient Follow-Up visit.||Phase 1||Recruiting||Drug: ADAIR 10 mg IR tablets|Drug: d-amphetamine sulfate|Drug: Placebo||More Info|
|Clarithromycin Mechanisms in Hypersomnia Syndromes||The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in two related conditions, narcolepsy without cataplexy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. This study will look at brain activity (on magnetic resonance imaging [MRI] and electroencephalogram [EEG] brainwaves), inflammation, bacteria living in the gut, and cerebrospinal fluid, to better understand how clarithromycin can reduce sleepiness. This study will recruit 92 participants who will be randomized to receive clarithromycin or a placebo for 14 days.||Phase 2||Recruiting||Drug: Clarithromycin|Drug: Placebo||More Info|
|A Study to Evaluate Safety, and Efficacy of SUVN-G3031 in Patients With Narcolepsy With and Without Cataplexy||This study is of an investigational drug called SUVN-G3031 as a possible treatment for narcolepsy with cataplexy or narcolepsy without cataplexy. The main purpose of this study is to learn how well the study drug works and how safe the study drug is compared to placebo.||Phase 2||Recruiting||Drug: SUVN-G3031|Drug: Placebo||More Info|
|A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy||The main aims of the study are:|
To check for side effects from TAK-994 and check what dose of TAK-994 participants can tolerate.
To check what dose range provides adequate relief of narcolepsy symptoms.
To check how much TAK-994 stays in the blood of participants, over time.
|Phase 2||Recruiting||Drug: TAK-994|Drug: Placebo||More Info|
|An Open Label Study of FT218 in Subjects With Narcolepsy||An Open Label Study to Evaluate Long-Term Safety and Tolerability of a Once Nightly Formulation of Sodium Oxybate for Extended-Release Oral Suspension (FT218) and the ability to switch from twice-nightly immediate release sodium oxybate to once-nightly FT218 for the Treatment of Excessive Daytime Sleepiness and Cataplexy in Subjects with Narcolepsy||Phase 3||Recruiting||Drug: FT218||More Info|
Top Treatments in Research
|Agent||Class/Mechanism of Action||Development Status||Company||Clinical Studies||More Information|
|TAK-994||Oral orexin agonist - novel, orally available OX2R-selective agonist with >700-fold selectivity against orexin 1 receptor.||Phase II||Takeda Pharmaceutical Company||More Info||More Info|
|FT218||Extended-release formulation of sodium oxybate||Phase III||Avadel Pharmaceuticals||More Info||More Info|
|SUVN-G3031||Orally-bioavailable Histamine H3 Receptor Inverse Agonist||Phase II||Suven Life Sciences Limited||More Info||More Info|
|AXS-12 (reboxetine)||Selective norepinephrine reuptake inhibitor thought to modulate noradrenergic activity to promote wakefulness, maintain muscle tone and enhance cognition||Phase II||Axsome Therapeutics||More Info||More Info|
† Genetic and Rare Diseases Information Center (GARD) - PO Box 8126, Gaithersburg, MD 20898-8126 https://rarediseases.info.nih.gov