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01 Sep 2020

Narcolepsy: causes, symptoms, treatment

Narcolepsy: causes, symptoms, treatment Narcolepsy: causes, symptoms, treatment

Narcolepsy is name given to pathological attacks of severe drowsiness that occur as a result of diseases of the central nervous system. Narcolepsy is characterized by a loss of control over the change in sleep and wakefulness, and a person may fall asleep in completely inappropriate conditions, even while doing work and driving a car. Most often, this disease occurs in men aged 15-30 years. Often, narcolepsy, if not detected in time, causes accidents.

Why does narcolepsy occur?

All causes of narcolepsy can be divided into several groups. The main causes of narcolepsy are:

- Severe mental and physical fatigue;
- Craniocerebral trauma of varying severity;
- Psychological trauma, strong emotions;
- Burdened heredity;
- History of general somatic infections and infections of the nervous tissue;
- Disturbances in the work of the endocrine glands and pituitary gland;
- Pregnancy.

As a result of the effect of a certain cause in the brain, a failure occurs in the zones that are responsible for the change in the "sleep-wake" cycles. In narcolepsy, REM (Rapid eye movement sleep) sleep occurs much earlier than in a healthy person, and the nature of these disorders is not clear. Experts put forward the theory of damage to certain areas of regulation in the brain, as well as immune disorders. Studies show that narcolepsy may be associated with a deficiency in the body of a special substance orexin, which is involved in the regulation of sleep and waking processes.

Narcolepsy symptoms

narcolepsy symptoms

- Severe daytime sleepiness, bouts of falling asleep while working, driving, talking, etc.;
- Cataplexy is a sudden general weakness against the backdrop of any intense emotion, whether negative or positive, amazement, laughing or crying. The duration of an attack is usually from a few seconds to several minutes. An attack of catalepsy is often followed by falling asleep.
- Sleep paralysis is total immobility that continues for some time after waking up (from a couple of seconds to several minutes). A person is fully conscious, can assess the situation, but is not able to move.
- Daydreams are vivid dreamlike visions that are most often accompanied by anxiety. Visions appear either at the time of falling asleep or upon awakening. Patients can see people or objects, hear voices or music.

Diagnosis and treatment of narcolepsy

One can suspect the disease on one's own by daytime sleepiness, but an accurate diagnosis can only be made by a specialist (somnologist, neurologist, psychiatrist) after conducting diagnostic tests, including encephalography, polysomnography, MSLT test, etc. Today, narcolepsy is considered an incurable disease, however, with the correct selection of the drug, it is possible to significantly facilitate a person's life and reduce the manifestation of symptoms.

Table 1. Drugs most commonly used to treat narcolepsy
and their pharmacological properties

Pharmacological properties
Increase the release of monoamines (DA> NE >> 5-HT). The primary effects of the drugs relate to the reverse flow of DA through the dopamine transporter (DAT). At high doses, inhibition of the accumulation of monoamines via the vesicular monoamine transporter (VMAT) and other effects are observed. The D isomers are more specific for dopamine transmission and are the best stimulants. They exert a certain influence on cataplexy (especially L-isomers) due to adrenergic effects at high doses. Available as racemates or as the pure D-isomer, and in various release modes. High potential for addiction when using immediate release forms. Large doses are associated with increased blood pressure and possible cardiac complications.
The profile is similar to that of amphetamines, although it is more lipophilic, with increased penetration in the central nervous system due to the presence of the methyl group. Currently available only as an immediate release form. High potential for addiction development.
Blocks the absorption of monoamines (DA> NE >> 5-HT). Does not affect upstream or VMAT. Short half-life. Available as racemate or pure D-isomer, and in various release modes. High potential for addiction when using immediate release forms.
Also known as L-deprenyl, a type B MAO inhibitor that converts in vivo to L-amphetamine and L-methamphetamine.
Modafinil *
Fewer peripheral side effects. Average potency substance. The mode of action is still a matter of debate, although it is likely associated with the relatively selective suppression of DA reuptake. Available as a racemate. Minimal dependence potential, therapeutic effect is slightly lower compared to amphetamines or methylphenidate. Long half-life of the R-isomer, the profile of the latter is close to the racemate, except for the dosage.
Tricyclic antidepressant. Monoamine reuptake inhibitor (NE> 5-HT >> DA). Demonstrates anticholinergic effects. All antidepressants immediately act on cataplexy, although their sudden withdrawal can induce pronounced rebound phenomena.
Tricyclic antidepressant. Monoamine reuptake inhibitor (5-HT> NE >> DA). Demonstrates anticholinergic effects. The active metabolite is desmethylcromipramine (NE>> 5-HT> DA). No specific in vivo.
Venlafaxine *
A specific serotonin and epinephrine reuptake blocker (5-HT≥HA), a very effective agent, although it sometimes causes nausea and dyspepsia. Compared to other antidepressants, it probably has less effect on sexual function. A mild stimulant with a short half-life, preferably in sustained release forms.
Duloxetine *
Close to venlafaxine, but slightly stronger agent due to its long half-life. Rarely associated with hepatotoxicity.
Atomoxetine *
A specific adrenaline reuptake inhibitor, usually indicated for attention deficit hyperactivity disorder. A mild stimulant with a short half-life. Suppresses appetite.
Specific serotonin reuptake inhibitor (5-HT >> NE = DA). The active metabolite of norfluoxetine exhibits more adrenergic effects. High therapeutic doses are often required.
Sodium oxybate * May act through specific GABA-B or GHB receptors. Decreases DA release. Requires intake at least twice a night, immediately affects disturbed night sleep. Therapeutic effects regarding cataplexy or daytime sleepiness may begin to take place within weeks to months from the start of treatment. Side effects include nausea, weight loss, and psychiatric disorders. As with any sedative agent, it is used with caution in hypoventilation or sleep apnea.
Abbreviation/definitions 5-HT - serotonin; DA - dopamine; MAO, monoamine oxidase; NE- norepinephrine; GABA-B - gamma-aminobutyric acid type B receptor GHB - gamma-hydroxybutyric acid.
* A drug that can be considered a first-line agent for narcolepsy / cataplexy, given its benefit / side effect profile compared to other drugs.

Table 2. Therapeutic protocols for the use of drugs,
which are indicated in the treatment of narcolepsy

The drug with the minimal number of side effects and the wakefulness-promoting effect comparable to amphetamines. It exists in the form of a racemic mixture at a dose of 100 and 200 mg, it is prescribed once or twice a day (in the morning and at lunchtime), the maximum therapeutic dose is 400 mg / day. Also available as R-Modafinil (Armodafinil) (50, 150 and 250 mg doses), about twice the strength of racemic modafinil by weight when constant. The most common side effect remains headache, which, however, can be avoided by gradually increasing the dose. Monitoring of possible allergic reactions is necessary, especially in children.

It is more potent than modafinil but has more potential side effects. It can replace modafinil if a long-acting form of the racemic mixture of any isomer is prescribed, usually at a dose of 20-40 mg/day. Different drugs and forms of release can show quite different interindividual effects. As a base drug, an immediate release medication (5-10 mg) is useful to relieve drowsiness, to maintain activity levels throughout the day (taking food right away), or in urgent situations (need to drive).

They are used similarly to methylphenidate, it is desirable to give preference to forms of sustained release. May be more effective than methylphenidate in some patients. Heart rate and blood pressure monitoring is required. Allergic reactions are highly possible.

Highly effective agent at low cost. Like all antidepressants, it acts quickly on cataplexy. May show very good action at 25 mg/day in the morning or evening, although daily doses of 75 mg and even 150 mg are usually required. Side effects include dry mouth, sweating, constipation, blurred vision, and orthostatic hypotension. The medication is contraindicated in persons with cardiac conduction disorders. Tricyclic antidepressants are not used in open-angle glaucoma.

Effective daily doses of 37.5-150 mg (maximum - 300 mg). Mild stimulant, short half-life, long-release forms preferred. With a sudden cancellation, possible psychiatric complications (shooting-pain sensations in the body) and rebound cataplexy. A high level of treatment compliance is required. The main reason for discontinuation of the drug is gastroenterological complications, in particular constipation. Low doses are helpful in children.
Similar to venlafaxine, but stronger and has a longer half-life. Effective daily doses are 20-40 mg (maximum 60 mg). When taking the drug, manifestations of hepatotoxicity rarely occur, so it should be avoided with alcohol abuse.
A mild stimulant and anti-cataplexic agent, therefore, it can be used in the therapy of drowsiness or cataplexy itself. The short half-life requires a twice daily dose. Effective daily doses are 10-60 mg (maximum 80 mg). Suppresses appetite. Urinary retention is possible as a side effect. Heart rate and blood pressure monitoring is required. Low doses are helpful in children.
Due to its very long half-life, it is suitable for stable therapy. With cataplexy, high therapeutic doses are often prescribed. Useful for concurrent anxiety disorder.
Sodium oxybate
ACTIVE for all symptoms of narcolepsy
It is prescribed at night, effective for insomnia, hypnagogic hallucinations, sleep paralysis. The effect on cataplexy and daytime sleepiness is evident immediately after starting treatment and peaks after a few weeks. In adults and adolescents, the initial dose is 4.5 g at night (for a double dose - at bedtime and in the middle of the night), in children before puberty - 3 g/per night, followed by increasing the dose to 6-9 g at night (on average - 4.5-6 g). The most common side effects are nausea and loss of appetite. Psychiatric complications are possible, especially in patients with an anxious premorbid background - to level them, sometimes it is necessary to supplement treatment with a specific serotonin reuptake inhibitor.

Post by: Emma Ager, MD, Copenhagen, Denmark

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