MODAFINIL DEPENDENCE

Dr. Vaidarshi Abbagoni, MBBS graduate from Mediciti Institute of Medical Sciences, Hyderabad;

Dr. Prithvi Gaur, Final year MBBS student

Abstract:

Modafinil is generally a low addiction potential drug and it is used in adolescents with ADHD disorder. This article talks about the addiction potential of modafinil in the student population. A young adolescent was presented to the psychiatry outpatient clinic in requirement of high doses of modafinil and after a thorough history, it was realized that this patient was consuming increasing doses of the drug to maintain its neurochemical effects. This case report describes a young patient who was prescribed modafinil for his ADHD and consumed incremental doses of the drug to maintain the levels of attention and developed an addictive potential to the drug. (1)

Introduction:

Modafinil is chemically composed of (2-[(diphenylmethyl) sulfinyl] acetamide). (Figure 1). It exhibits robust effects on catecholamines, serotonin, glutamate, gamma amino-butyric acid, orexin, and histamine systems in the brain and is well-tolerated. Modafinil is less related to side effects such as excess locomotor activities, anxiety, jitteriness, or rebound effects than traditional stimulants. It not only has a waking effect but is also known for its mood-brightening and memory-enhancing effects. (2) Modafinil has also been tried on disease-related fatigue, attention-deficit disorder, Alzheimer’s disease, age-related memory decline, depression, idiopathic hypersomnia, cognitive impairment in schizophrenia, myotonic dystrophy, post-anesthesia grogginess, everyday cat-napping, and jet-lag treatment.

Due to its dopaminergic activity, Modafinil has been used in the treatment of cocaine and methamphetamine abuse. Even though the abuse is not frequent, it’s still possible to encounter patients abusing the substance specifically in patients with a history of alcohol or substance abuse. There are rare reports of Modafinil abuse in literature. The maximum dosage of the drug in these cases was 3,000 mg/day. (1)

In this report, we present a case with high-dose (5,000 mg/day) Modafinil dependence who had no history of alcohol or substance abuse and was diagnosed with attention deficit hyperactivity disorder (ADHD)

Case:

A young 24-year-old male visited the psychiatry clinic and reported a history of difficulty in listening to classes since school, was easily distracted, had issues with concentration and attention, low academic performance, and performance anxiety for which he had multiple psychological visits. His history was supported by his parents. He was diagnosed with ADHD but the parents refused treatment due to concerns with the side effects of the stimulant drug. Modafinil could be purchased over the counter and so he started taking  50mg/day of modafinil without any doctor’s suggestion. To maintain the stimulant effects, he increased his dosage without any supervision to 300-400mg/day for 2 years. Due to his demanding symptoms with the unsupervised consumption of modafinil, he presented to a different psychiatry clinic, where a short-acting methylphenidate 20mg/day was prescribed.  In addition to Modafinil, he consumed methylphenidate 60 mg/day. Though he discontinued this drug later, due to worsening of symptoms. He soon started consuming Modafinil 100mg 5 times a day and each time he quit he experienced withdrawal symptoms like fatigue, vivid and unpleasant dreams, sleeping irregularities, anxiousness, and functional impairment.

Modafinil cannot be purchased without a prescription according to the recent regulations in Turkey, therefore the patient had difficulty with access and thus he presented to the clinic with difficult symptoms. He reported consuming 5,000 mg/day of Modafinil for 1 month. After evaluation, he was admitted to our psychiatry ward with the initial diagnosis of “stimulant use disorder” according to DSM-5 classification.

The patient was prescribed alternative drugs like Lorazepam 2.5 mg/day, Risperidone 1 mg/day, and Ketiapin 25 mg/day. But due to his symptoms with discontinuation of modafinil he experienced cravings, psychomotor agitation, sweating, tremor, fatigue, and his treatment was modified to Diazepam 15 mg/day, Ketiapin 100 mg/day, Risperidone 2 mg/day. After discharge from the ward, the patient was followed up on his first outpatient visit and he reported poor compliance with his medications and requested a prescription of modafinil. He never returned after this visit.

Discussion:

      Pharmacology:

Modafinil (2-[(diphenylmethyl) sulfinyl] acetamide) is an exclusive psychostimulant. (Figure 1). Its normal life is 12 to 15 hours and it is readily absorbed after single or multiple oral doses. It reaches peak plasma concentrations 2-4 hours after administration and can be detected in plasma and urine. It is highly lipophilic and also binds to plasma proteins, especially albumin. It achieves steady-state plasma concentrations within 2 to 4 days of repeated dosing. Food in the gastrointestinal tract slows down its rate of absorption. It is eliminated primarily in the liver by amide hydrolysis and partially through urine. Drug-drug interaction of modafinil is seen with ethinylestradiol and triazolam. (3)

Mechanism of Action:

Modafinil affects the dopamine, norepinephrine, and catecholamine transporters which accounts for its psychostimulant effect. (Figure 2)

      Sequelae:

Modafinil promotes wakefulness and is seen to improve cognitive functions such as attention, learning, and memory. It is also used to treat fatigue in patients with cancer and depression. Soldiers to combat fatigue using modafinil. It allows for mood-brightening and elevating lethargy. (2)

      Use:

In sleep-deprived individuals, modafinil is seen to improve mood, fatigue, sleepiness, and cognition but not for a long duration. However, in non-sleep-deprived individuals, its use to improve cognition is controversial. In healthy individuals both sleep-deprived and non-sleep-deprived, improvement in recognition memory, working memory, and sustained attention can be seen. (2)

It is seen to improve excessive sleepiness and severity of illness in narcolepsy, shift-work sleep disorder, and obstructive sleep apnoea. Many studies also approve its use to treat children suffering from attention deficit hyperactivity disorder (ADHD). (1)

Adverse Effects:

It may affect the autonomic nervous system in the periphery and causes hypertension and an increase in the heart rate. (3) Its use must be restricted in patients with heart disease because of the excessive peripheral autonomic activation. (3) It may also induce sympathomedullary activation presenting as a fight or flight response in the patient. It also causes insomnia, headache, nausea, and nervousness. In children and adolescents, it may cause decreased appetite, weight loss, and serious dermatological manifestations.

      Modafinil Abuse:

Modafinil abuse is seen in individuals to combat the fear of academic failure, meet high work demands and overcome procrastination while boosting motivation. (4)

Modafinil mimics amphetamine in its affinity for dopamine receptors which may explain its abuse potential, although modafinil is seen to have less abuse potential than amphetamine. Modafinil dependence has been rarely reported, however, increased dopamine resulting in increased stimulation of dopamine receptors may cause its compulsive use. The previously discussed case reports the highest dose dependence of 5000mg/day.

Modafinil use is especially seen in students, people with long working hours and patients with ADHD as the psychostimulant effects of modafinil cause its dependence in patients to improve their productivity levels and concentration while combating lethargy and fatigue. (4)

Though the abuse potential of modafinil is rare, it warrants further investigation to allow for the development of prophylactic care and preventive measures.

Conclusion:

With increasing stress levels and the requirement of greater productivity to keep up in a competitive world, drugs like modafinil may be consumed to achieve greater heights. However, these cause long-term health concerns. Hence, stress management and an understanding of work-life balance are important to prevent abuse of psychostimulant drugs like modafinil. The effects of modafinil require further investigation helping to determine prophylactic action.

Acknowledgment:

Alacam, H., Basay, O., Tumkaya, S., Mart, M., & Kar, G. (2018). Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder. Psychiatry Investigation, 15(4), 424–427. https://doi.org/10.30773/pi.2016.10.25

References:

1.   Alacam, H., Basay, O., Tumkaya, S., Mart, M., & Kar, G. (2018). Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder. Psychiatry Investigation, 15(4), 424–427. https://doi.org/10.30773/pi.2016.10.25

2.   Kim D. (2012). Practical use and risk of modafinil, a novel waking drug. Environmental health and toxicology, 27, e2012007. https://doi.org/10.5620/eht.2012.27.e2012007

3.   Minzenberg, M., Carter, C. (2008) Modafinil: A Review of Neurochemical Actions and Effects on Cognition. Neuropsychopharmacol 33, 1477–1502. https://doi.org/10.1038/sj.npp.1301534

4.   Teodorini RD, Rycroft N, Smith-Spark JH. (2020) The off-prescription use of modafinil: An online survey of perceived risks and benefits. PLoS One.15(2):e0227818. doi: 10.1371/journal.pone.0227818.

Image references:

1.   Costa, Vera & Carvalho, Félix & Bastos, Maria & Carvalho, Rui & Carvalho, Márcia & Remio, Fernando. (2012). Adrenaline and Noradrenaline: Partners and Actors in the Same Play”.10.5772/36070.

2.   Schroeder, Christoph, and Jens Jordan. (2012) Norepinephrine transporter function and human cardiovascular disease. American journal of physiology. Heart and circulatory physiology. (303)11:H1273-82

3.   https://en.m.wikipedia.org/wiki/Dopamine_transporter

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