Thursday, January 19, 2017

Treatment of Narcolepsy

Hey Awesomites!
This is the last post of the four-post series on Narcolepsy. So let's begin.


Treatment for narcolepsy is multifold. Although no specific target therapy or cure exists for narcolepsy, a combination of treatments can aid in controlling the symptoms and enable the patient to prune back to normal activities of life. It includes a combination of counseling, lifestyle changes and certain medications.

Counseling and support groups:-  Narcoleptic patients often suffer from depression and anxiety. Many symptoms of narcolepsy including the sudden- onset sleep attacks, cataplexy (loss of muscle control), microsleep episodes, etc. are a cause of embarrasment and may even prove to be disastrous in some situations for the patient as well as those around. This may lead to feelings of emotional distress in the patient and thus may eventually worsen the condition. Fear of falling asleep during work hours, driving, or in a meeting forces the patient to become secluded and withdrawn.
So it is absolutely essential to reach out to a psychologist or a counselor or a support group for narcoleptics and get help to cope up with the effects of this disorder. Being with others who have also suffered or are suffering from the same condition may help reduce the sense of isolation and remove the stigma that the patient may feel. Sharing experiences with others and getting to learn from their experiences as a narcoleptic may inspire and encourage the patient as well.

Lifestyle modifications:- The patients are more comfortable in making lifestyle changes to reduce the suffering rather than to be put on medications for life. Daytime habits such as good nutrition, exercise, and many others must be taken into consideration as they play a pivotal role in helping to maintain a proper sleep-wake cycle.
- Maintain sleep hygiene to rule out an element of chronic sleep deprivation. Planned naps can prevent unplanned lapses into sleep. Limit daytime naps to 15 minutes or so, as longer naps risk entering into slow- wave sleep stage 3 potentially inducing grogginess or sleep- inertia, thus leading to deleterious consequences on night- time sleep.
- Avoid caffeine, alcohol and nicotine as these substances interfere with sleep- wake cycle.
- Exercise on a regular basis can increase metabolism and the person remains active during the day time.
- Avoid sedating medications unless necessary
- Good nutrition is a must to aim for a diet rich in whole grains, vegetables, fruits, low fat dairy products, and lean sources of proteins.
- Relaxation techniques such as breathing exercises, yoga and body massage are benefitting.

Pharmacotherapy:-
In most cases, stimulant medications are the mainstay of treatment. Modafinil is a well- tolerated CNS stimulant drug that has recently been tagged as the “crown prince of smart drugs.”  Just like other stimulants, it increases monoamine release and also elevates hypothalamic histamine levels. Therefore, it acts as a wake- promoting agent. This drug is to be given cautiously to patients suffering from any of anxiety or headache disorders as it may worsen the condition in such patients.

Methylphenidate and dexamphetamine are amphetamines with short duration of action and a higher rate of adverse effects especially hypertension and psychiatric effects. Initial dose is to be kept 5mg twice daily with a maximum daily dose of 60mg. Modafinil can be used in combination with either of the two amphetamines if daytime sleepiness remains problematic. These drugs should probably be avoided in pregnant women and those taking hormonal contraceptives.

Alternative agents for treating daytime sleepiness include selegiline, mazindol and nicotine. Nicotine patches help sleep drunkenness on waking. Many patients report a worsening of symptoms when giving up smoking.

Habituation and addiction with these drugs does sometimes occur but switching between drugs regularly can be effective, but not practical.

Sodium Oxybate is a relatively new drug for treating cataplexy and excessive daytime sleepiness. It is a GABA-B receptor agonist and is therefore extremely sedating. It has been used for criminal purposes as a “date rape drug” being a potential drug of abuse. It acts as a respiratory depressant and deaths have been reported in combination with alcohol or other CNS- depressant drugs. Despite these limitations, sodium oxybate is used as a first- line drug for narcolepsy with cataplexy in the United States. In the UK, it is more commonly being used in patients with refractory narcolepsy. Patients are well instructed priorly not to mix the drug with alcohol and if they do consume alcohol, they should not take sodium oxybate that night.
Sodium Oxybate may exacerbate sleep- disordered breathing and also interfere with normal sleep- wake cycle. So patients with sleep apnoea do not tolerate this drug well. Addiction to this drug harms the patient and is life- threatening!
Recent trials of over 80 patients have shown positive results in patients taking sodium oxybate and almost two- thirds of whom stay in it for long- term.

Experimental treatments have proved the beneficiaries of Immunomodulation therapy that acts on the basis that suppression of the immune- mediated attack on hypocretin- producing neurons may well modify the disease course. Intravenous immunoglobulins may produce improvement in symptoms in the patients within a few weeks of onset of narcolepsy with cataplexy.

Hypocretin agonists have also been proposed as a treatment modality in narcolepsy. Since there is lack of hypocretin in the lateral hypothalamus that is pathognomic for narcolepsy, intraventricular administration of hypocretin maintains wakefulness and suppresses cataplexy. Research has been going on development of a potent agonist of hypocretin receptors that is small enough to cross the blood- brain barrier.

The European Medicines Agency (EMA) has recently approved the use of Pitolisant for the treatment of narcolepsy with or without cataplexy. Pitolisant is an inverse agonist or antagonist histaminergic agent with selectivity for the H3 receptor. In a recent clinical trial on 259 patients, the drug was found to be effective and relatively safe. The 109 patients treated with pitolisant were observed to have decreased day time sleepiness and were more alert. Adverse effects of this drug include insomnia, nausea and headache. Pitolisant has not yet been approved for use in the US and is designated an orphan drug status. More research is still needed to explore more ways to treat and manage patients of narcolepsy with or without cataplexy.

Other novel therapies being explored for use in narcolepsy include histamine antagonists and melanin- concentrating hormone receptor antagonists.


Thats all. Do go through other posts in the series of Narcolepsy posts:

Role of Orexins in Narcolepsy
Clinical features of Narcolepsy
Diagnosis of Narcolepsy

- Jaskunwar Singh

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