Introduction
Narcolepsy is a chronic neurodegenerative disorder that onsets in childhood or early adulthood and equally affects men and women though the diagnosis is delayed in women. It is characterized by hypocretin-producing neurons in the hypothalamus of the brain. Because these neurons are crucial in regulating sleep and wake states, the individual suffers excessive daytime sleepiness as a result, even after completing their sleep cycles to the optimum level.
Narcolepsy severely impacts health, social life, education, and the professional and career prospects of the individual and presents a significant socioeconomic burden for the individual and society. Treatment options for narcolepsy are mainly in the form of medication and lifestyle changes, out of which Modalert-200 is most talked about because of its capacity to reduce sleepiness symptoms effectively without compromising patient safety.
A word on Modalert
Modalert -200 is the derivative of Modafinil, a potent psychostimulant regarded as the best treatment option for conditions of narcolepsy and excessive sleepiness. Modafinil was introduced in 1970 by Lafon Laboratories in France and, in due course, FDA approved for use in excessive sleep disorders. It is the first line of treatment for narcolepsy and Shifts Work Sleep Disorder and an off-label treatment option for multiple sclerosis and cancer-related fatigue.
Because of its generic status, Modalert -200 shares the same structure, pharmacodynamics, and mechanism as that of Modafinil while at the same time being more readily available and cost-effective. Modalert -200 effectively works on the neurotransmitter pathways, enabling the individual to stay awake, alert, and focused.
Modalert – the ideal solution for narcolepsy
It is important to understand that narcolepsy is not limited to excessive daytime sleepiness episodes. Narcolepsy patients exhibit symptoms of sleep paralysis, hypnagogic or hypnopompic hallucinations, and cataplexy, out of which narcolepsy with catalepsy represents 60-70% of diagnosed cases of narcolepsy. In such conditions, Modalert-200 blocks the dopamine and noradrenaline transporters from exerting their stimulatory effects.
Dopamine and Adrenaline are neurotransmitters that control brain states, vigilance, action, reward, learning, and memory processes and enhance the individual’s cognitive abilities. Consequently, their deficiency or imbalance impacts the orexin levels and causes abnormalities in energy homeostasis, stress-related behavior, and the body’s reward system. Orexin further excites the waking-active monoaminergic and cholinergic neurons in the hypothalamus and brain stems to maintain a long, consolidated waking period.
Several studies have shown orexin neurons to have reciprocal links with the hypothalamic nuclei regulating the feeding cycles. Additionally, they play an important role as a link between energy homeostasis and vigilance states. They even regulate goal-directed behavior and emotional states because of their link with the ventral tegmental nucleus.
The deficiency of orexin in narcolepsy patients impacts their wakefulness and cognitive capacity, creating a sensation of constant sleepiness coupled with a fuddled state of mind. The loss of orexin affects the REM sleep motor atonia-producing nuclei, causing cataplexy transient, sudden loss of voluntary muscle control brought on by a strong emotional trigger such as laughing or excitement.
Studies on the neurochemical and behavioral effects of Modafinil(Modalert-derivative) have suggested that it has a unique mechanism of action that is complex and different from other wakefulness-producing agents. Unlike psychostimulants like Cocaine, methylphenidate, and amphetamines that enhance dopamine levels by inhibiting dopamine reuptake through the dopamine transporter, Modalert indirectly works on the dopamine neurotransmitter by activating the orexin neurons in the lateral hypothalamus;
The orexin neurons, in turn, synthesize the hypocretin-1 and hypocretin-2 and send axons that manage the sleep regulation centers and keep the person alert and their cognitive stimulation activated. Other than its effect on orexin neurons, Modalert activates the histaminergic neurons in the hypothalamic tuberomammillary nucleus to keep the individual awake without developing a tolerance or addiction towards its CNS effects.
When stimulated by Modalert, the orexin neurons work on the cholinergic and non-cholinergic receptors in the basal forebrain and activate the glutamatergic synapses in the lateral hypothalamus, stimulating the person’s memory and learning process.
Studies about Modafinil and narcolepsy
In a 9-week randomized, placebo-controlled, 21-center clinical trial conducted to evaluate the effects of Modalert, 511 narcolepsy patients were enrolled in a study. Two hundred seventy-one patients naive to Modafinil received Modafinil-200 mg once daily for two weeks. Two hundred forty subjects previously using Modafinil were evaluated to observe the withdrawal effects after discontinuing it. Treatment with Modafinil resulted in improvement in the Multiple Sleep Latency Test and Maintenance of the Wakefulness Test with improvement in the patient’s self-assessment of sleep.
During the ensured course of treatment, the quality of nighttime sleep was not affected by using Modafinil. Headache was one of the significant adverse reactions observed in most narcolepsy patients enrolled in the study.
The subjects enrolled to observe the withdrawal effects of Modafinil did not experience any significant symptoms, and up to nine weeks of daily use, dependence on Modadifil was not observed at the dose levels studied. The sum total of the study made researchers conclude that Modafinil is an effective treatment for excessive daytime sleepiness in narcolepsy and can be safely used for up to nine weeks. It also indicated the safety and adequate tolerance of Modafinil. Based on the study, it can be safely assumed that Modalert-200, the generic equivalent of Modafinil, can be potent in dealing with narcolepsy and its excessive sleepiness.
Other studies have shown that Modalert can be used with tricyclic antidepressants, Ritalin, Serotonin-reuptake inhibitors, and anticonvulsants to deal with the other symptoms associated with narcolepsy. While greater effects are observed with higher doses, the safety profile is optimum in 200 mg of Modalert/ Modafinil.
Other conditions of excessive sleepiness and Modalert
Other than narcolepsy, Modalert has shown positive results in Shift Work Sleep Disorder patients and those with neurological disorder-induced tiredness, excessive sleepiness, and fatigue.
A comprehensive literature review was conducted to identify published studies assessing the effects of Modalert on fatigue coupled with excessive daytime sleepiness associated with neurological disorders, then randomized controlled trials were identified, including four parkinson’sParkinson disease studies, three multiple sclerosis studies, two traumatic brain injury, and one post-polio syndrome study. The effects of Modalert on 535 patients were evaluated, showing its benefits on Traumatic brain fatigue and Parkinson’s Disease. The study showed promising results of the medication in neurological disorder-induced excessive daytime sleepiness and its potential in dealing with symptoms of depression and fatigue.
Conclusion
Modalert is an ideal solution for narcolepsy and excessive sleepiness conditions, as numerous clinical trials and animal studies prove. But further studies must be conducted to determine its overall efficacy and effect on daytime sleepiness and cognitive qualities. Long-term usage can result in side effects and adverse reactions, and it should be used per the physician’s advice for the patient’s safety.
Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699169/
https://www.ncbi.nlm.nih.gov/books/NBK531476/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521685/
https://www.frontiersin.org/articles/10.3389/fnbeh.2013.00028/full
https://article.imrpress.com/journal/FBL/24/3/10.2741/4736/4736.pdf
https://www.nature.com/articles/1301534
https://pubmed.ncbi.nlm.nih.gov/10720292/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081802