Modafinil versus Armodafinil – Analysis Report


Defined as disturbances in the circadian cycle affecting the normal sleep time, sleep disorders left untreated can lead to a number of health complications. Sleep statistics have shown that 36% of adults in the UK suffer from sleep disorders. As many as 16 million suffer from sleep disorders out of which 31% have insomnia and 67% suffer from disrupted sleep. 27% report not getting more than 5 hours of sleep at night. Medications are the main treatment options in such conditions. Apart from keeping them awake, they are crucial for the individual to lead normal lives without lack of sleep affecting their work, academics or private life in any manner.

A word about Modafinil and Armodafinil

Both Modafinil and Armodafinil are eugeroic medications designed for treatment for excessive sleepiness at daytime in patients. Eugeroics are primarily defined as psychostimulants that work on the CNS to improve wakefulness and alertness with promoting increased focus in the patients. Unlike typical psychostimulants, these medications have much less addiction potential associated with their use. They can be safely used for extended time periods as per the physician’s treatment plan.

Molecular structure

Modafinil and Armodafinil are very similar yet differ considerably on the basis of their enantiomers or molecular structures. Modafinil is a racemic mixture containing equal amounts of R and S enantiomers. Armodafinil is an enantiopure i.e. it contains only R enantiomer. This makes it a purer compound than Modafinil. Both Armodafinil and Modafinil work by binding themselves to the dopamine reuptake pump resulting in increased production of extracellular Dopamine, serotonin and histamine. Despite that Armodafinil is 1.33 times more potent than Modafinil in exerting its cognitive stimulation effects.

The reason can be attributed to the higher affinity of its R enantiomers. R enantiomer has more affinity than S enantiomer for dopamine transporter with a longer half-life (approximately 10-14 hours.). The S with a smaller half-life has a shorter duration than R enantiomer. It also gets eliminated in a quicker time interval. It is the lack of S enantiomer in Armodafinil and specific presence of R enantiomer that enables its prolonged lasting span.

Conditions treated by them

Modafinil and Armodafinil are both FDA approved for treatment of disorders of

  • Narcolepsy – A neurological disorder characterized by overwhelming sleepiness in day time and sudden attacks of sleep.
  • SWSD – Shift Work Sleep Disorder a problem mostly experienced by night shift workers whose work schedules to against the circadian rhythms.
  • Sleep Apnea – It is a sleep disorder in which the patient repeatedly stops and starts breathing during sleep resulting in disturbed sleep patterns.

Off-label Modafinil is recommended for reducing the fatigue levels of cancer patients or those undergoing active chemotherapy sessions. In a study conducted on 37 cancer patients and administered Modafinil, significant improvements in FSS (Fatigue Severity Scale) were observed without any adverse effects. The use of Modafinil is also being evaluated for fatigue reduction in multiple sclerosis patients. Studies conducted on patients diagnosed with multiple sclerosis and administered Modafinil have shown improvement in their fatigue and exhaustion. It has even been well tolerated by them. Apart from these Modafinil is used as a useful option in dealing with the side-effects of accident induced dementia or neuroleptic treatment of depression.

Off label use of Armodafinil in cancer patients did not yield any satisfactory results. Use of Armodafinil in multiple sclerosis patients showed positive results in terms of memory. Other factors like executive function, visual memory, processing speed and self – reported fatigue remained insignificant. It showed significant improvement in ADHD patients with the potential to improve cognitive function in ADHD patients through its use.

Which is more effective?

Because of its enantiopure nature, Armodafinil has a longer half-life and exerts its effects for a longer time than that of Modafinil. Both Modafinil and Armodafinil are administered in specific doses to the patients for the effects to start showing in a brief period of time.

Modafinil is available in strengths of 100mg and 200mg out of which 200mg is the more commonly used dose. Armodafinil is available in strengths of 75mg, 100mg, 150mg and 250mg out of which 150mg is the most commonly used dose.

Modafinil takes around 30-60 minutes to start working and achieves peak plasma concentrations within 2-4 hours after administration. Modafinil lasts for around 12-15 hours in the body after which it is removed through feces and other metabolic waste.

Armodafinil starts working within 15 -25 minutes of intake and achieves peak plasma concentrations within 1-2 hours of use. Because of its selective R-enantiomer, Armodafinil stays in the body for 20 hours or more after which it is metabolized and eliminated.

150 mg of Armodafinil achieves better wakefulness effects than 200 mg of Modafinil with no adverse effects or addiction potential associated with its use. This makes Armodafinil a better option especially for narcolepsy and SWSD patients who require the added hours of wakefulness for better functioning.

But it depends on the user, their systemic conditions and the treatment plan of the medical practitioner whether Modafinil or Armodafinil is the better option for them.

What do studies say?

In order to compare and evaluate the best of the two drugs, data from three randomized studies was pooled and dose normalized to 200mg dose for each drug. All the subjects included in the study were otherwise healthy and received single doses of the drug. Till a particular time after drug ingestion, both medications showed similar Cmax values. After that time period, plasma concentrations started declining in a monophasic manner with Armodafinil resulting in longer time of effect of the drug. In Modafinil, the concentrations started declining in a biphasic manner resulting in it getting eliminated in a shorter duration of time. The overall results of the study showed that despite having similar half-lives, Armodafinil showed improved wakefulness because of its pharmacokinetic profile.

Other studies have shown that Modafinil shows variable wakefulness promoting effects throughout the day. Some patients towards the end of the day required 400 mg or 600mg split dose of Modafinil to continue the cognitive stimulation. Armodafinil with its 200mg dose could maintain wakefulness even in the later part of the day owing to its long elimination half- life.

Cost comparison with generic status

The main disadvantage of Modafinil has always been its price. A single pill of branded Modafinil or Provigil can cost up to $24.64 per pill. Generic Modafinil through the brands of Modalert, Modvigil and others were introduced to make the drug available to more people by means of cost effectiveness. Even for generic versions, the price of Modafinil can go as high as around $9 per pill.

Armodafinil in comparison is cost effective than its counterpart for the generic versions and brand versions. A leaf of Nuvigil containing 30 tablets can cost 361$ whereas generic Armodafinil or Waklert can cost as low as $6 or even less depending on the online site you are ordering from. This makes Armodafinil more popular from the angle of cost effectiveness and enables it to be available to a wider range of users with sleep disorders.

That said, both Modafinil and Armodafinil with their generic counterparts are Schedule IV medications with a number of laws governing their selling, possession and use. They are not available readily over the counters. You need a physician’s prescription for obtaining Modafinil or Armodafinil from pharmacies or online portals. It is the growing use of Modafinil and Armodafinil as a nootropic among healthy individuals that has led to this legal implementation of their status in countries worldwide.

Side effects and drug interactions

Headache, nausea, nervousness, dizziness, diarrhea, indigestion, dry mouth, anxiety and decreased appetite are some of the common side effects associated with the use of Modafinil and Armodafinil. It has been observed though that the frequency of side-effects in Armodafinil is slightly less than Modafinil. Studies assessing the long term efficacy and tolerability of Armodafinil in patients with sleep disorder have observed Armodafinil to be effective and well tolerated even after 12 months of use. Modafinil and Armodafinil used in clinical trials were well tolerated by pediatric patients with narcolepsy over longer than 5 years of follow-ups.

But as of now they have not been FDA approved for pediatric use. Additionally, they share the same drug interactions and precautions. Neither Modafinil nor Armodafinil should be used concomitantly with psychiatric medications, heart medications or medications used in cancer treatments. The safety of these medicines has not been proved in pregnant or breastfeeding ladies and should be avoided in such cases. Intake with food delays the time taken for the medications to start working and should be avoided as much. Most importantly, Modafinil or Armodafinil should not be taken at the same time as this can result in serious overdose symptoms and be life threatening for the user.

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