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How Modafinil Works for Depression?

Introduction

The major depressive disorder has been identified as the largest contributor to mental health problems throughout the world with its severity further increased as a result of accompanying factors like high prevalence and high recurrence rate. The tendency of the problem to be chronic further adds to the worry of health experts. The WHO has estimated approximately 300 million people or 4.4% of the global population are suffering from the illness with an upward increase in the problem noticed since 2005. Of a large number of mental health disorders, depression ranks second highest after anxiety and is followed by alcohol use disorders and drug use disorders.

Defined as an umbrella phenomenon encompassing a number of sub-conditions within it,  the problem is characterized by symptoms of low energy, lack of sleep, loss of interest, and appetite changes among others.

Depressive Symtoms

What makes depression more complicated to treat is less regarding the prevalence of individual symptoms and more about the combinations of symptoms that diagnosed patients experience. The combination of the symptoms varies from patient to patient with each combination requiring a treatment plan customized for it. Sometimes people end up diagnosed with moderate to severe depression but without any of the above-mentioned symptoms accompanying the diagnosis. In such conditions, treatment measures for depression need to be carefully monitored so as to obtain the desired results without impacting the treatment quality.

Why Modafinil for depression?

Usually, antidepressants are the first choice of treatment for patients diagnosed with depression. But long term use of the drug results in a gradual lessening of its effectiveness. A recent cause of worry among psychologists and mental health experts is the fact that a third of depressed patients receive unsatisfactory/ negligible benefits through the use of antidepressants even when used in conjunction with psychological counseling. Those who do respond to antidepressants face the side effects of fatigue and trouble sleeping, decreasing the effectiveness of the anti-depressants to a considerable extent.

Since its advent in the 1970s, Modafinil Canada has been recognized as a powerful psychostimulant with cognitive stimulation properties. Modafinil exerts its effects on the serotonin, dopamine, and adrenergic receptors of the CNS, similar to the areas of action of antidepressants to bring out their therapeutic functions; making clinical experts conclude that it can be used as an adjunctive therapy alongside antidepressants for enhancing their therapeutic properties.

Another important aspect observed by researchers was the wakefulness/ alertness advantage offered by Modafinil on depression patients. Along with fatigue and excessive anxiety episodes, depression is also characterized by insomnia tendencies followed by excessive drowsiness at the workplace. The two main problems faced by depression patients at work mainly absenteeism i.e taking sick leave from work and presenteeism i.e present at work but not functioning as before or in the required manner; both can be resolved through the cognitive advantages offered by Modafinil.

In fact, the remission rates of depression patients have also been found to be reduced during the use of Modafinil. Cognitive dysfunction is a major side-effect associated with depression that has a tendency to persist even after mood and other symptoms improve. Playing an important role in the professional and academic well-being of the individual, problems associated with cognition eventually impact the effectiveness of antidepressants and result in remission risk of the problem.

But the cognitive effects of Modafinil enable the user to manage their cognitive imbalance and get on track to a normal life without depression symptoms. While studying the therapeutic effects of Modafinil on depression patients, researchers have further found episodic memory ( memory of everyday events including past personal experiences like birthdays and significant dates)  and working memory ( information about addresses, putting together the sequence of instructions/ stories) both to be improved through the use of Modafinil medication.

What do studies say?

In a retrospective chart review of the effects of Modafinil on depression as monotherapy and as adjunctive therapy, the results were positive in both conditions. For the study, subjects with diagnosed clinical depression who failed one or more adequate antidepressant treatments were enrolled under the guidance of the medical practitioner. Of the 45 subjects, 15 were put on Modafinil monotherapy while the remaining 30 subjects were put on adjunctive therapy. For either subgroup, the depression rating scales showed significant improvement within 2 weeks (mono) and 3 months (adjunct) of Modafinil treatment respectively.

The study proved that Modalert 200mg has the potential to be beneficial to people with major depression even when unresponsive to other treatments.

Apart from these, Modafinil has also been proved an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression; a condition characterized by low moods, persistent feelings of despair, and other depressive symptoms in the winter season.

Can Modafinil substitute antidepressants?

So far, researchers have postulated the effects of Modafinil on the CNS and its potential as an adjunct medication. But research is still ongoing about the implementation of Modafinil used as monotherapy for depression. Among the wide variety of postulations offered regarding the anti-depressant use of Modafinil, some state that it exerts its effect by agonism of central alpha 1adrenergic receptors in the cortex while others contribute its effects to agonistic effects on nor-adrenaline receptors.

In a 6 month observational study performed on patients with partial response to antidepressants, the use of Modafinil in doses of 200-400mg per day caused significant improvements in sleepiness within the first week of use and in fatigue within the second week. Three major factors related to depression i.e cognitive confusion, daytime sleepiness, and residual fatigue were successfully treated by the use of Modafinil alongside the main medication.

The overall view of researchers in this context was Modafinil has a complicated antidepressant efficacy through its effects on the neurotransmitters. Additionally, low doses of Modafinil like 100mg /day doses are sufficient for producing anti-depressant effects on the individual. But at present, it can only be used as an off-label recommendation. Further studies are required to declare its use solely as monotherapy for depression and regulate its use in this direction.

 

References

http://https://ourworldindata.org/mental-health#depressions

http://https://www.nature.com/articles/s41398-020-0842-6

http://https://pubmed.ncbi.nlm.nih.gov/16035049/

http://https://pubmed.ncbi.nlm.nih.gov/15306145/

http://https://www.sciencedaily.com/releases/2013/11/131127115355.htm

http://https://www.eurekalert.org/news-releases/593558

http://https://www.sciencedirect.com/science/article/pii/S2451902216301811

http://https://arsiv.dusunenadamdergisi.org/ing/fArticledetailsbe59.html?MkID=1137#:~:text=In%20conclusion%2C%20it%20is%20believed,on%20antidepressants%20will%20be%20beneficial.

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