Is Modafinil Effective for Narcolepsy?
Modafinil was first developed in the 1970s in France as a drug to treat sleep disorders. Since 1998, the drug gained popularity as a go-to treatment for narcolepsy, as well as other similar disorders like obstructive sleep apnea and shift work sleep disorders. Currently, modafinil is a very common, safe drug most frequently prescribed for narcolepsy, besides its off-label use as an anti-sleep drug.
What is Narcolepsy?
Narcolepsy, a kind of neurological disorder, disrupts the body's capacity to regulate the sleep-wake rhythm. The daytime sleepiness of narcoleptics is extreme and uncontrollable. Furthermore, individuals could suddenly nod off even in the middle of discussions or other regular activities.
Narcolepsy comes in type I and type II varieties. Whereas type II narcolepsy just involves excessive sleepiness, type I narcolepsy also includes cataplexy, an abrupt failure of muscular control. Despite the fact that cataplexy is a symptom of narcolepsy, normal muscle control is unaffected by this illness. The ability to regulate one's sleep-wake cycle is completely lost or diminished in narcolepsy. Most of our daily behaviors, including sleep and appetite, are governed by a physiological cycle known as the circadian rhythm, that is typically found in healthy individuals. A complicated balancing act between nerve impulses and hormones keeps the circadian cycle in check. The brain system in charge of regulating sleep is impacted by the occurrence of narcolepsy. The body no longer has a choice over when it should go to sleep and when it should stay awake as a result. Narcoleptics experience a sudden fall asleep as a result of this. A duration of heavy, non-REM sleep is followed by brief bursts of mild REM sleep in a 90-minute sleep cycle that characterizes normal sleep. In the particular circumstance of narcoleptics, slow wave sleep, or REM sleep is absent, resulting in an instantaneous deep slumber with impaired motor function.
Narcolepsy's typical signs and symptoms may include the following:
- Excessive daytime sleepiness (EDS): In EDS, a person feels excessively sleepy during the day despite obtaining enough night's sleep. One feels sluggish and lethargic, and because of a lack of energy, even focusing on work might be difficult. Memory gaps happen, and one may even feel depressed or exhausted.
- Cataplexy - Cataplexy is the abrupt loss of control over a group of muscles. The symptoms of cataplexy can range from slurred speech to a full collapse of the body, contingent on which muscle is involved. Intense emotions including shock, excitement, or fury commonly trigger cataplexy.
- Hallucinations: Narcolepsy is frequently linked to hallucinations. Narcoleptics may have strong visual illusions that are frequently accompanied by aural or tactile experiences. These happen either when you wake up or when you are going to sleep. Hypnagogic hallucinations are those that happen just before you go to sleep, whereas hypnopompic hallucinations are those that happen just as you wake up. Narcolepsy patients frequently experience both, and they are typically far more intense or realistic than typical dreams.
- Sleep Paralysis: Although it can be compared to a more severe kind of hallucination, sleep paralysis is mechanistically distinct from hallucinating. When your brain's cognitive regions are active and thinking or imagining things while your motor control regions are sleeping or not awake, this condition is known as sleep paralysis. This results in the inability to move, talk, or respond, as well as strong visual and sensory feelings. Sleep paralysis episodes might last anywhere from a few seconds to several minutes.
- Sleep disruption: Narcolepsy is frequently accompanied by disturbed sleep in which sufferers struggle to fall asleep as a result of thoughts or inert body motions. Additionally, it is challenging to sustain sound sleep, and narcoleptics may wake up several times during the night.
How to know if you have narcolepsy?
Narcolepsy is often seen as hypersomnia resulting in the condition remaining undiagnosed altogether. Individuals suffering from narcolepsy simply believe that they are fatigued and do not seek medical help. In the cases of extreme cataplexy or hallucinations help is sought but the probability of misdiagnosis still remains high. The standard methods of diagnosing narcolepsy include:
- Medical history and physical examination
- Sleep reports: For a few weeks, the doctor may urge patients to keep a log of their symptoms including when they sleep, wake up, or nap.
- Polysomnogram: This is carried out at a sleep center or laboratory. It's an overnight examination that records issues with the sleep cycle by continuously measuring people while they are asleep. A PSG might show if people enter REM sleep at odd moments during their sleep cycle. It can eliminate other issues that could be the source of any symptoms.
- MSLT: A specialized clinic or lab may also do multiple sleep latency tests. The test is conducted throughout the day to assess your propensity to nod off and determine whether specific aspects of REM sleep occur at odd hours during the day. You'll often space out your four or five brief naps by two hours.
What are the common causes of narcolepsy?
Researchers are still unsure of the exact pathophysiology of narcolepsy. According to the available data, it is seen as a neurological condition linked to a loss of control over the sleep-wake cycle. The sleep-wake pattern is a component of the body's typical circadian rhythm, as was previously stated. The hypothalamus, a structure located in the forebrain, has absolute control over circadian rhythm. The hypothalamus controls the whole system through the cyclical release of various hormones and neurotransmitters. For instance, the neurotransmitters serotonin and dopamine act in opposition to one another to promote sleep and alertness, respectively. The hormone melatonin has a significant influence on the sleep-wake cycle as well. In investigations involving narcolepsy, however, abnormalities in the routes of these compounds were not discovered. It was discovered that a different hormone called hypocretin is what causes narcolepsy. We still don't know the precise molecular process by which hypocretin causes narcolepsy.
Narcolepsy is thought to have a hereditary cause. The likelihood that narcolepsy will run in a person's family increases, which lends credence to the idea that the disorder may be inherited. Another vulnerability of narcolepsy is age. Narcolepsy is more likely to appear in individuals aged between 15 and 25, after which it is most likely to last the rest of their life. Although there hasn't been any progress in identifying the precise gene that causes narcolepsy, research is still ongoing in this area.
Common treatments of narcolepsy
There is no cure for narcolepsy, but medications and lifestyle modifications can help you manage the symptoms.
The use of psychostimulants, which stimulate the central nervous system, is the primary method of treating narcolepsy. Modafinil or armodafinil are routinely used by physicians to begin treating narcolepsy patients. Modafinil and armodafinil are much less dangerous than previous stimulants, and they don't produce the euphoria and depression that are usually related to psychostimulants. Although they are stimulants, modafinil or armodafinil have no negative effects on how your brain normally functions as these are only mild DRIs. The medications in this class, known as eugeroics, are those that increase bodily awareness. Anxiety, nauseousness, and headaches are a few possible modafinil side effects, notwithstanding their rarity. For the treatment of certain individuals, amphetamine salts or other stimulants may be required. These medications work quite well, despite the possibility of addiction. Nevertheless, they also produce extensive undesirable side effects that affect other important organs of your body, like the heart.
Selective serotonin reuptake inhibitors (SSRIs)
These are widely recommended by medical professionals to treat the signs and symptoms of hypnagogic encephalopathy and cataplexy. With the use of SSRIs, delusions, sleep paralysis, as well as REM sleep, are also inhibited. Some possible adverse effects include gaining weight, having trouble sleeping, and having gut problems.
These are a class of classic antidepressants that are typically administered to treat cataplexy. These, however, have unpleasant side effects, such as dry mouth and disorientation.
Emerging Treatment Methods
Certain over-the-counter medicines, including allergy and cold remedies, might make you sleepy. Your doctor will probably advise against using these drugs if you have narcolepsy.
Drugs that affect the histamine biochemical network, hypocretin supplementation, hypocretin pharmacogenomics, and immunotherapy are some of the new therapies being studied for narcolepsy, although more study is required before any of these treatments may be prescribed at a doctor's office.
Modafinil for narcolepsy
As noted above, modafinil is the safest and most effective treatment used for narcolepsy. Due to its safe nature, it is also easy to find Modafinil smart drug for sale online where you can buy the drug as per your requirements without any hassle. Since we aim to discuss whether modafinil is effective against narcolepsy, it would be wise to understand how modafinil works to decide whether it is truly effective in treating narcolepsy.
Modafinil is a eugeroic drug designed to promote alertness in the body. It is a stimulant that stimulates the CNS. Much like some other classic stimulants like Adderall or Ritalin, Modafinil and Armodafinil (an enantiomer of Modafinil) act by increasing the amount of dopamine in the body. However, this activity is at a much controlled and safer rate when performed by Modafinil leading to very low risks of drug dependency. In this factor, Modafinil is a safer and better choice over traditional psychostimulants which run high risks of drug dependency and addiction. Furthermore, modafinil also exhibits negligible side effects, making it one of the safest drugs to treat narcolepsy.
Let us now understand how modafinil functions as a eugeroic and the role of dopamine in this process.
Source: Springer Publication
As I have already mentioned, eugeroics are drugs whose exclusive function is to promote wakefulness, that is, reduce sleepiness. Dopamine is a neurotransmitter produced in our body that is responsible for creating alertness, focus, and elevated physical and cognitive capacity in our bodies. In other words, our mind is more alert, focused, and active in the presence of dopamine. In a healthy body, dopamine is secreted by the brain when there is a need for alertness or focus. The molecule passes through neurons to carry the signal for attention from the brain to the rest of the body. Once the signal is transduced, the excess dopamine outside neurons is reuptaken by dopamine receptors to remove it from the extracellular regions.
Modafinil acts as a DRI, or Dopamine Reuptake Inhibitor. It binds to the dopamine receptors and prevents the reuptake of dopamine. This in turn causes the accumulation of dopamine in the extracellular region. This prolongs the effect of dopamine in the body, thus helping it to maintain focus and alertness for a longer duration. In this way, modafinil succeeds in treating the symptom of excessive sleeping caused by narcolepsy.
Narcolepsy remains an incurable condition at the moment. Treatment of narcolepsy primarily involves treating the symptoms of the condition and alleviating them. Modafinil is a safe drug that helps treat narcolepsy by promoting wakefulness in the body, thereby preventing abrupt, and excessive sleeping. As discussed in the previous section, Modafinil achieves this by increasing the amount of dopamine in the body through active inhibition of dopamine reuptake at neural synapses. Although dopamine is not directly involved in causing narcolepsy, the accumulation of dopamine can majorly reduce the effects of narcolepsy by making the body more alert and focused and preventing abrupt sleep. Since there is no proper understanding of how hypocretin, the hormone responsible for narcolepsy results in the condition, targeting hypocretin for the treatment of narcolepsy, albeit potentially effective, is not available to us at the moment. Thus, modafinil forms the best treatment for narcolepsy at the moment, not to mention, the safest as well.