Armodafinil Vs Modafinil

What is Armodafinil? What is Armodafinil used for?

Armodafinil is Generic name for a drug that is used to treat extreme sleepiness caused by sleep disorders in order to improve wakefulness. Chemically it is (R)-(−)-enantiomer of the racemic modafinil.

It works by changing concentrations of certain body substances that are unbalanced and located in the brain area that controls sleep and wakefulness.  Armodafinil indications are: sleep apnea, narcolepsy and shift work sleep disorder (sleepiness in people who work at night or on rotating shifts during scheduled waking hours or those who difficulty falling asleep or staying asleep during scheduled sleeping hours).

However, it is frequently used off-label for the management of attention deficit hyperactivity disorder – ADHD, major depressive disorder and chronic fatigue syndrome. It has been also shown that armodafinil may improve vigilance in air traffic controllers.  FDA approved armodafinil for use in 2007.  It can be found on the market with Brand name Nurvigil.

Can armodafinil be used for the treatment of schizophrenia?

In 2010, it has been showed that an armodafinil’s phase II study as an adjunctive therapy in adults with schizophrenia had failed to meet the primary endpoints, and the clinical program was terminated. However, a study published later that year revealed that patients with schizophrenia treated with this drug showed less negative symptoms of schizophrenia.

What is Modafinil? What is Modafinil used for?

Modafinil is a Generic name for a drug that is used to treat excessive sleepiness disorders caused by sleep apnea, narcolepsy, or shift work sleep disorder in order to improve wakefulness in adults.  It works by changing concentrations of certain body substances that are unbalanced and located in the brain area that controls sleep and wakefulness.

Modafinil improves short-term memory thus allowing patients to stay awake for long periods of time. In some occasions it is used for military performance enhancement especially for pilots and soldiers during combat situations, and it is known as a “super drug”.  It can be found on the market with Brand names such as: Provigil, Alertec, Modavigil.  FDA approved modafinil in 1998 for the treatment of narcolepsy.

The European Medicines Agency recommended modafinil only for sleepiness associated with narcolepsy, because of the risk for development of neuropsychiatric disorders or skin hypersensitivity reactions.

How Armodafinil and Modafinil work in the body?

Although these drugs are chemically very similar, there are some little differences in their mechanism of action. However, the exact mechanisms of these actions are not yet fully revealed. Both drugs inhibits dopamine reuptake in the brain as they both contain R modafinil enantiomer. But, modafinil also contain S enantiomer and that is why it also expresses different actions.

Armodafinil is a single-isomer of modafinil. The exact mechanism of armodafinil action is still not known. Armodafinil is eugeroics type of drugs, stimulants that provide long-lasting mental arousal. Armodafinil is not agonist or antagonist of neither receptors nor inhibitor or activator of enzymes which are relevant for regulation of sleep/wake.

Also it is not a direct- or indirect agonist of dopamine receptors. However, in vitro, studies found that both armodafinil and modafinil bind to the dopamine transporter and inhibit reuptake of dopamine. However, for modafinil it has been shown that activates glutamatergic paths while inhibiting GABA.

Modafinil is known to have a less abuse potential compared to other stimulants because it does not causes significant pleasurable and euphoric effects. Possible mechanism of modafinil actions could be a synergistic combination including direct inhibition reuptake of dopamine, indirect noradrenalin reuptake inhibition and orexin activation. Modafinil has also partial alpha 1B-adrenergic agonist activities.

Armodafinil and Modafinil dosage and forms

Both drugs are available in the form of tablet. Armodafinil is manufactured as Nurvigil in doses of 50 mg, 100 mg, 150 mg, 200 mg and 250 mg. Modafinil is manufactured in doses of 100 and 200 mg. Armodafinil is most commonly administered at a starting dose of 150 mg and it is taken once in the morning for wakefulness-related disorders.

There is no evidence that doses above 150 mg offer additional therapeutic benefit. Modafinil starting dose for most wakefulness-related disorders is 200 mg and should be taken once in the morning.  Due to individual sensitivities, some people may prefer a lower dose of 100 mg over the 200 mg.

There is no evidence that doses exceeding 200 mg have additional therapeutic benefit. After oral administration they are absorbed rapidly, and their maximum levels are expected after 2 hours for armodafinil and 2-4 hours for modafinil.

Similarities between Armodafinil and Modafinil

Both drugs are known as eugeroics or “wakefulness-promoting agents”. They are different and non-habiting compared to more potent psychostimulants such as Adderall which are habit-forming. Both drugs are available in the form of tablet.

Their approved indications are: narcolepsy, obstructive sleep apnea and shift work sleep disorder. However they are commonly used off-label due their wakefulness promoting effects. Their main mechanism of action is very similar as they both inhibit dopamine reuptake, however there are some difference.

Their side effects profile and incidence are mostly same. Headache, dizziness, nausea, nervousness and insomnia are most common side effects from both drugs. Both drugs are investigated for their use for ADHD, Chronic fatigue syndrome, Cognitive enhancement, Depression, Drug addiction and Jet lag.

Both drugs are known to have a low abuse potential when it is used as recommended. They are classified as a “Schedule IV” controlled substance.

Armodafinil was designed because of theoretically better efficacy from modafinil, however studies have failed to prove this. Studies found that that both drugs are more effective than placebo or the treatment of excessive daytime sleepiness.

Preferences for one of this drug over the other are generally subject to individual variation. However, Provigil- modafinil remains to be the most popular drug compared to armodafinil – Nuvigil and other eugeroics.

Difference between Armodafinil and Modafinil

The main difference between armodafinil and modafinil is that armodafinil contains only the “R” enantiomer of modafinil while modafinil is a racemic compound that contains both the “S” and the “R” enantiomers.

Theoretically R- enantiomer should be far more efficient than RS racemic compound. So armodafinil is actually updated version of modafinil. As a result of containing only “R” enantiomer, armodafinil has for 2 more hours longer effects than modafinil.

Armodafinil duration of effects is calculated to 8 hours, while modafinil is about 6 hours. Also “S” enantiomer of modafinil has a short-half life time, and because of that, armodafinil has longer duration of effect, and maybe higher potency and efficacy.

Nuvigil (Armodafinil) vs. Provigil (Modafinil): Comparison

Some findings suggest that armodafinil is twice more potent than modafinil, but degree of armodafinil potency is still unknown. Some evidence tells that armodafinil lower doses may have equal efficacy as higher modafinil doses.

However, beyond certain doses, no additional benefits can be achieved from both drugs. In comparison, it is expected for armodafinil dose of 150 mg per day give the same effects as 200 mg per day of modafinil.  Also, armodafinil onset of action maximum is after 2 hours, while modafinils maximum is after 2 to 4 hours.  That is why armodafinil is thought to provide symptomatic relief for up to 2 hours longer than modafinil.

Modafinil has been researched for the treatment of attention-deficit/hyperactivity disorder – ADHD, delayed sleep phase syndrome,  syndrome of chronic fatigue, but also depersonalization disorder linked with schizophrenia, depression, fibromyalgia, jet lag,  drug addiction, Parkinson’s disease, multiple sclerosis, and weight loss.

Even though the fact that it isn’t officially approved for these conditions, it is still commonly used and prescribed off-label.  Nuvigil has been researched for many of the same conditions such as ADHD, chronic fatigue syndrome, jet lag and drug addiction.

One different use for Nuvigil over Provigil which is investigated is armodafinil possibility to be adjunct therapy in schizophrenia treatment, particularly for negative symptoms.  Some data estimate that a most of the prescriptions for these drugs are for off-label such as cognitive enhancement.

Which one is expensive, Armodafinil or Modafinil?

Modafinil is approved for use in 1998, while armodafinil is approved in 2007. Armodafinil is only available as a Nurvigil while modafinil is also available in generic forms, because the patent for Provigil had expired, allowing other companies to manufacture generic versions. So, generic versions of modafinil are always compared to brand named.

The generic version of modafinil will cost between $150 and $305 for a 30 day use.  But, the “brand name” Provigil is known as one of the most expensive drugs on the market, costing between $790 and $805 for Provigil 100 mg tablets and well over $1000 for a 200 mg tablets.

Nuvigil is a newer drug and is not yet available as a generic.  The lowest Nuvigil dose of 50 mg costs between $195 and $210 for a 30 day use, and doses from 150 to 250 mg costs between $570 and $600 for a 30 use.

So, the cheapest option is generic modafinil, then Brand named armodafinil called Nuvigil, and the most expensive is Brand named modafinil called Provigil.

Armodafinil and Modafinil abuse

Both armodafinil and modafinil are classified as “Schedule IV” substances in the United States.  This means that these drugs are having a lower potential for abuse compared to other drugs or substances in “Schedule III.”  Also, the drugs in the “Schedule IV” class have medically accepted uses in the United States.

However, it is possible that armodafinil and modafinil may be a subject of abuse.  Both drugs, if abused may cause psychological or physical dependence.  Because of their low potential for abuse, prescriptions for these drugs can be refilled up to 5 times within a 6 month term.

Armodafinil and modafinil are not popular as party drugs and thus they are unlikely to be abused.  Their dopamine inhibition effects are considered significantly weaker than psychostimulants.  Many patients compare their effect with effects of very high doses of caffeine rather than effects of psychostimulants.

The potential of abuse rises when these drugs are used off-label without medical supervision.  For example, modafinil is commonly used for weight loss, optimize occupational or productivity enhancement of academic performance. These unapproved uses are more likely to result in abuse and dependence.

Armodafinil and Modafinil side effects

Armodafinil and modafinil have similar side effects profiles. They may cause next side effects:

Common side effects:

  • Headache (45-50%)
  • Decreased appetite (16%)
  • Rhinitis (11-15%)
  • Abdominal pain (12%)
  • Nausea (11%)
  • Nervousness (6-10%)
  • Syncope (1-5%)

Side effects with unknown incidence:

  • Arrhythmia
  • Hypotension
  • Hypertension
  • T-wave changes
  • Amnesia
  • Anxiety
  • Cataplexy
  • Chills
  • Depression
  • Dizziness
  • Epistaxis
  • Fever
  • Insomnia
  • Paresthesia
  • Reversible psychosis (rare)
  • Tremor
  • Drug hypersensitivity syndrome
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis due to drug
  • Anorexia
  • Diarrhea
  • Dry mouth
  • Mouth ulcer
  • Vomiting
  • Abnormal LFT
  • Chest pain
  • Neck pain
  • Dyspnea
  • Pharyngitis

Postmarketing Reports:

  • Aggression
  • Psychomotor hyperactivity

Armodafinil and modafinil withdrawal effects

Neither armodafinil nor modafinil is thought to have any withdrawal symptoms.  Reports ensure that no matter of dosing and time of usage, these drugs can be abruptly stopped without causing any withdrawal symptoms.  However, if these drugs are used for a long time period they can cause some effects when they are abruptly stopped.

Common symptoms of withdrawal include: cognitive impairment, sleepiness, fatigue and resurgence of original condition.

Warnings and precautions during armodafinil and modafinil use

These drugs should never be used if:

  • Patient is allergic to any ingredient in armodafinil or in modafinil
  • Patient have a history of developing a rash after taking modafinil or armodafinil
  • Patient have or had a history of certain heart or heart valve problems such as mitral valve prolapse or left ventricular hypertrophy

Before using these medicines, patients should contact their doctors if they are:

  • pregnant, planning to become pregnant, or are breast-feeding
  • taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
  • allergic to medicines, foods, or other substances
  • having liver problems, kidney problems, heart problems or high blood pressure
  • habing a history of mental or mood problems such as depression, mania, psychosis suicidal thoughts or actions, or alcohol or other substance abuse or dependence
  • taking a monoamine oxidase inhibitor (MAOI) such as phenelzine

Some drugs may interact with armodafinil or modafinil. Patients should avoid combining these drugs with next medicines:

  • Erythromycin or ketoconazole, these drugs may increase the risk of armodafinil’s and modafinil’s side effects
  • Phenobarbital, Carbamazepine, rifampin because they may decrease their effectiveness
  • Clomipramine, desipramine, hydantoins (such as phenytoin),  diazepam, omeprazole, propranolol, or warfarin because the risk of their side effects may be increased Cyclosporine, hormonal products (such as birth control pills, and ceratin hormone replacement therapy), quetiapine,  midazolam or triazolam because their effectiveness may be decreased by armodafinil or modafinil.

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