Nuvigil and Provigil are both drugs that were approved by the FDA for the treatment of excessive daytime sleepiness. Both drugs act as eugeroics and are considered “wakefulness-promoting agents” in that they are distinct from more potent, habit-forming psychostimulants (e.g. Adderall). Provigil was initially approved in the late 1990s to help treat narcolepsy.
Although the drug was successful in treating narcolepsy, many individuals sought out the drug as a performance enhancing agent, particularly as a nootropic. A series of patent issues for Cephalon Inc. (the manufacturer of Provigil) lead the company to engineer an upgraded version of Provigil called “Nuvigil.” Nuvigil contains solely the R-enantiomer of modafinil whereas Provigil contains both the “R” and “S” enantiomers of modafinil.
Nuvigil was approved by the FDA in 2007 for the treatment of excessive daytime sleepiness associated with narcolepsy. Despite the fact that Nuvigil was intended to be a more effective successor to Provigil, there is no evidence to suggest superior efficacy. Preferences for one drug over the other are generally subject to individual variation.
Nuvigil vs. Provigil Comparison Chart
Below is a chart comparing the eugeroics Nuvigil and Provigil. Provigil is an older medication and has been subject to more off-label usage as a result. The two medications are thought to be very similar in their mechanism of action and wakefulness-promoting effect.
|Approved uses||Narcolepsy. Obstructive sleep apnea. Shift work sleep disorder.||Narcolepsy. Obstructive sleep apnea. Shift work sleep disorder.|
|Dosages||50 mg/150 mg/200 mg/250 mg||100 mg/200 mg|
|Manufacturer||Cephalon Inc.||Cephalon Inc.|
|Legal Status||Schedule IV (US)||Schedule IV (US)|
|Mechanism of action||Functions by inhibiting reuptake of dopamine and is thought to act as an indirect D2 receptor partial agonist. It is believed to also elevate histamine levels in the hypothalamus and increase concentrations of other neurotransmitters such as norepinephrine and serotonin. It may activate orexin peptides via stimulation of orexin receptors (OX1 and OX2). It may also increase glutamatergic concentrations / decrease GABAergic activation – and increase electronic coupling.||Functions by inhibiting reuptake of dopamine and elevating histamine levels in the hypothalamus. It also increases levels of other monoamines such as norepinephrine / serotonin / and activation of orexin peptides. Specifically it may stimulate orexin receptors (OX1 and OX2) to promote wakefulness. The drug may also activate glutamatergic circuits / inhibit GABA neurotransmission / and enhance electronic coupling.|
|Half life||15 hours||12 hours|
|Common side effects||Dizziness. Headache. Insomnia. Nausea. Nervousness.||Dizziness. Headache. Insomnia. Nausea. Nervousness.|
|Date approved||June (2007)||(1998)|
|Effect duration||8 hours||6 to 8 hours|
|Investigational uses||ADHD. Cognitive enhancement. Chronic fatigue syndrome. Depression. Drug addiction. Jet lag. Negative symptoms of schizophrenia.||ADHD. Cognitive enhancement. Chronic fatigue syndrome. Delayed sleep phase syndrome. Depersonalization. Depression. Drug addiction. Fibromyalgia. Jet lag. Multiple sclerosis. Parkinson's disease. Weight loss.|
Nuvigil vs. Provigil: What’s the difference?
The primary difference between Nuvigil and Provigil is that Nuvigil contains just the “R” enantiomer of modafinil and Provigil contains both the “S” and the “R” enantiomers. They are both manufactured by Cephalon Inc. and both are thought to have nearly identical mechanisms of action. If you’re knowledgeable about antidepressants, a good analogy is that: Nuvigil is to Provigil what Lexapro is to Celexa.
It’s just an upgraded version of an older drug that’s been repackaged in a more efficient formula. The reason it has been repackaged is largely a result of the fact that the patent for Provigil had expired, allowing other companies to manufacture generic versions. By creating Nuvigil, Cephalon Inc. was able to promote a new version of their older drug at a premium price, thus increasing their earning potential.
Nuvigil is thought to elicit a slightly longer duration of effect (2 more hours) than Provigil as a result of containing only the R-enantiomer. The S-enantiomer found in Provigil has a much shorter half-life than its R-enantiomer counterpart, meaning Provigil’s effect may not be as potent, efficient, or long-lasting when compared to Nuvigil.
Both Nuvigil and Provigil are considered “Schedule IV” substances in the United States. Under this classification, the drugs are regarded as having a low potential for abuse relative to other drugs or substances in “Schedule III.” Furthermore, the drugs in the “Schedule IV” class have medically accepted uses in the United States.
That said, it is possible that Nuvigil and Provigil may be subject to abuse. Abuse of either of these drugs could lead to psychological or physical dependence – more likely the former than the latter. Due to their low potential for abuse, prescriptions for these drugs can be refilled up to 5 times within a 6 month term.
Most people don’t take eugeroics as party drugs and therefore they are unlikely to be abused. Although they do elicit dopamine reuptake inhibition (DRI) effects, the degree to which they inhibit dopamine is considered significantly weaker than psychostimulants. Many people have compared their effects to high doses of caffeine as opposed to psychostimulants like Adderall.
The abuse potential increases when these substances are used on an off-label basis without medical supervision. For example, some people use Provigil for weight loss, enhancement of academic performance, or optimize occupational productivity. These unapproved uses may be more likely to result in abuse and dependence upon the drug for functioning.
Cost: Which is more expensive?
Those looking to take a eugeroic to treat a condition associated with excessive daytime sleepiness (e.g. narcolepsy), may want to compare prescription prices. Due to similarities between Provigil and Nuvigil, most insurance companies will want you to take whichever one is cheaper. If you are paying out of pocket or don’t have very good insurance, you’ll probably also want to take the cheaper of the two.
Provigil is an older drug that’s been on the market since 1998 and is available as a generic (modafinil). The generic version of Provigil (modafinil) will cost anywhere from $150 to $305 for a 30 day supply. The “brand name” Provigil is one of the more expensive drugs on the market, costing between $790 and $805 for a 30 count of 100 mg pills and well over $1000 for a 30 count of 200 mg pills.
Nuvigil is considered a newer drug and is not yet available as a generic. The lowest 50 mg dose of Nuvigil costs between $195 and $210 for a 30 count, and between $570 and $600 for a 30 count of any other dosing option (i.e. 150 mg, 200 mg, 250 mg). The cheapest format is generic modafinil, followed by brand name Nuvigil, with the most expensive option being brand name Provigil.
Dosage & Formats
Nuvigil and Provigil are manufactured in “tablet” format and are absorbed rapidly after oral administration. The peak effect of each drug is thought to be achieved within 2 hours of consumption, though this may be delayed slightly with food consumption or enhanced via fasting. Nuvigil is manufactured in doses of 50 mg, 150 mg, 200 mg, and 250 mg.
Provigil is only manufactured in doses of 100 mg and 200 mg. The starting dose of Provigil for most wakefulness-related disorders is 200 mg 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 offer additional therapeutic benefit.
Nuvigil is manufactured in a greater number of dosing increments compared to Provigil. It is typically administered at a starting dose of 150 mg, taken once in the morning for wakefulness-related disorders. The drug is considered by some as being twice as potent as Provigil due to the fact that it solely consists of the “R” enantiomer.
There is no evidence that exceeding doses of 150 mg offers additional therapeutic benefit. By comparison, Nuvigil has more dosing options, but many people don’t care due to the fact that some users cut Provigil in half for smaller doses. Some individuals may like the fact that Nuvigil is manufactured with double the dosing options compared to Provigil.
Efficacy: Which drug is more effective?
There is no clear evidence that Nuvigil is superior in efficacy to Provigil as a wakefulness-promoting agent or vice-versa. Nuvigil is a newer substance and is considered more potent than Provigil, but the degree to which it is more potent is unknown. Some speculate that Nuvigil is nearly twice as potent as Provigil due to the fact that it contains solely the “R” enantiomer of modafinil, whereas Provigil (modafinil) is comprised of a mix of the “R” and “S” enantiomers.
The “S” enantiomer of modafinil is known to have a shorter duration of effect, and is considered less potent than the “R” enantiomer. Anecdotal evidence suggests that lower doses of Nuvigil may be equal in efficacy than higher doses of Provigil. Both drugs seem to hit a therapeutic ceiling, meaning that beyond certain doses, no additional benefits can be attained.
The therapeutic ceiling for Provigil is thought to be 200 mg per day and the therapeutic ceiling for Nuvigil is thought to be 150 mg per day. Nuvigil’s onset of action peaks at 2 hours, whereas Provigil’s onset of action peaks between 2 to 4 hours. Additionally, Nuvigil is thought to provide symptomatic relief for up to 2 hours longer than Provigil.
From a perspective of duration of effect and potency, Nuvigil may be advantageous. However, there remains no head-to-head comparison of efficacy between these drugs. Some research suggests that Nuvigil may deliver superior wakefulness to Provigil.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19663523
Mechanisms of action
Due to the fact that both drugs are very similar, there isn’t thought to be significant discrepancies in their respective mechanisms of action. There may be subtle differences due to the fact that Nuvigil only contains the “R” enantiomer and Provigil contains both the “R” and the “S” enantiomers. The specific mechanisms of action for each drug are poorly understood by the medical community.
Provigil is thought to inhibit reuptake of the dopamine transporter, thus increasing extracellular levels of dopamine. Its dopaminergic effect is thought to be significantly less than amphetamines and other psychostimulants. Research also shows that Provigil increases levels of both norepinephrine in the hypothalamus and ventrolateral preoptic nucleus, and levels of serotonin in the amygdala and prefrontal cortex.
Some studies suggest that Provigil also activates peptides in the brain called “orexins.” These peptides are responsible for promoting wakefulness and deficiencies can result in excessive sleepiness. In animal models, Provigil was confirmed to stimulate orexin receptor 1 (OX1) and orexin receptor 2 (OX2). It also may also stimulate glutamatergic circuits, while inhibiting GABAergic neurotransmission.
Another effect of Provigil is its ability to enhance “electronic coupling,” thereby increasing efficiency of neural communication. This enhancement of electronic coupling this believed to increase gamma brain waves, which may also aid in promotion of wakefulness and cognitive function. Nuvigil is thought to have the same mechanism of action as Provigil.
The “R” and “S” enantiomers of modafinil elicit similar effects in animals, but the “R” enantiomer is more potent and delivers a longer effect. The “R” enantiomer is thought to have nearly three-fold the binding activity for dopamine and norepinephrine transporters than the “S” enantiomer. Other than differences in enantiomer composition, there shouldn’t be major differences in Nuvigil and Provigil with regards to mechanisms of action.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19197004
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17920581
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/
Nuvigil and Provigil are approved by the FDA for the treatment of sleep-wakefulness disorders such as narcolepsy. Both were initially approved for the treatment of narcolepsy, and were since approved for the treatment of obstructive sleep apnea (OSA) and shift work sleep disorder (SWSD). Due to the fact that Provigil hit the market (1998) earlier than Nuvigil (2007), it has been more heavily investigated as a non-traditional (off-label) treatment for an array of conditions.
Provigil has been investigated for the treatment of attention-deficit/hyperactivity disorder, chronic fatigue syndrome, delayed sleep phase syndrome, depersonalization disorder, depression, drug addiction, fibromyalgia, jet lag, multiple sclerosis, Parkinson’s disease, and weight loss. Despite the fact that it isn’t officially approved for these conditions, it is still commonly prescribed. Nuvigil has been investigated for many of the same conditions such as ADHD, chronic fatigue syndrome, drug addiction, and jet lag.
One different investigational use for Nuvigil over Provigil is as an adjunct to treat schizophrenia, particularly the negative symptoms (e.g. avolition). Some sources estimate that a majority of the prescriptions for these eugeroic drugs are for off-label purposes such as cognitive enhancement. By comparison, the approved medical uses for these drugs are the same and investigational uses are similar.
The fact that Provigil has been around longer than Nuvigil and is available under the generic name of “modafinil” has contributed to its popularity. There remains a grey-market for Provigil sales online from unauthorized third-party sources, generally based in foreign countries (outside the United States). The mystique surrounding Provigil’s off-label use as a nootropic has lead many people to actively seek out the drug to enhance cognitive function and productivity.
As of 2014, profits from Nuvigil sales were thought to exceed $400 million, while in 2007 sales of Provigil exceeded $800 million. Provigil has been around since the 1990s and has remained the most popular eugeroic on the market. Nuvigil is being heavily promoted by Cephalon Inc. as a result of Provigil’s generic availability. Sales of Nuvigil and its popularity is expected to grow in coming years.
Most people that are knowledgeable of Provigil (Modafinil) are not necessarily knowledgeable of Nuvigil (Armodafinil). Those that know of Nuvigil generally know that it is the successor to Provigil. Provigil is universally regarded as the more popular eugeroic drug, and Nuvigil is a newer, lesser-known spin-off of Provigil with a similar name.
The side effects resulting from Nuvigil and Provigil are thought to be similar. For some people less side effects may be experienced as a result of solely ingesting the “R” enantiomer (Armodafinil) whereas others may find less side effects from a racemic mix of the “R” and “S” enantiomers (Modafinil). Common side effects associated with both drugs include: dizziness, headache, insomnia, nausea, and nervousness.
Perhaps the side effects from Nuvigil may be longer-lasting due to the fact that the drug itself is thought to elicit a greater duration of effect. Additionally, lower doses of Nuvigil may trigger side effects comparable to higher doses of Provigil as a result of its increased potency. In some cases, users of these drugs may experience serious skin reactions (e.g. Stevens-Johnson syndrome).
Neither is thought to have a favorable side effect profile over the other. The severity and number of side effects experienced may be related to the dosage of either drug as well as individual physiology.
Neither Nuvigil nor Provigil is thought to have any withdrawal symptoms. Many reports claim that regardless of dosing and duration of usage, these drugs can be stopped abruptly without any discontinuation symptoms. Whether there is a withdrawal period or not is largely a matter of medical debate and subjectivity.
In the past, many drugs were thought to have no discontinuation effects. It wasn’t until decades later that researchers discovered that there were in fact discontinuation effects and drug companies admitted these symptoms. Due to the fact that these are highly potent drugs that promote wakefulness and there’s no biological free lunch, most people should expect withdrawal symptoms.
Common symptoms of Nuvigil withdrawal and Provigil withdrawal include: cognitive impairment, fatigue, sleepiness, and resurgence of original condition (e.g. narcolepsy). It may take days, weeks, or even months for the brain to restore homeostatic functioning following eugeroic usage.
Similarities (Recap): Nuvigil vs. Provigil
Based on ingredient composition, Nuvigil and Provigil are very similar drugs.
- Abuse potential: Both drugs are considered to have a low potential for abuse when used as medically suggested. Abuse potential increases when individuals begin using the drugs on an off-label basis or with the intention of taking supratherapeutic doses in attempt to attain a “high.”
- Drug type: Each of these drugs is classified as a eugeroic or “wakefulness-promoting” agent.
- Efficacy: Evidence suggests that both Nuvigil and Provigil are significantly more effective than a placebo in double-blind, randomized clinical trials for the treatment of excessive daytime sleepiness.
- Formats: Both drugs are available in “tablet” format.
- Interactions: These drugs are thought to have similar contraindications due to similar ingredients. That said, contraindications may be subject to variation and you should always consult a medical professional to discuss interactions.
- Investigational uses: Each of these substances has similar investigative uses including: ADHD, chronic fatigue syndrome, and jet lag.
- Manufacturer: Cephalon Inc. is responsible for the creation of both Nuvigil and Provigil.
- Medical uses: The drugs are approved for the treatment of excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work sleep disorder.
- Legal status: Each are classified as a “Schedule IV” controlled substance. This means there is a low potential for abuse, but they are refillable up to 5 times in 6 months.
- Neurotransmission: These substances are thought to have similar mechanisms of action in regards to how they affect neurotransmission.
- Side effects: Common side effects associated with each drug are similar and include: dizziness, headaches, insomnia, nausea, and nervousness.
- Withdrawal: Most medical experts suggest that there is no withdrawal associated with either drug, and that if there are withdrawal symptoms, they quickly dissipate. The most common withdrawal symptoms are increased fatigue and sleepiness.
Differences (Recap): Nuvigil vs. Provigil
Below are some general differences between Nuvigil and Provigil.
- Cost: The cost of Nuvigil for a 30 day supply ranges between $195 and $210 (for 50 mg) and between $570 and $600 (for all higher doses). The cost of generic Provigil (modafinil) is within the range of $150 and $305 for a 30 day supply. Brand name Provigil remains expensively priced between $800 and $1200 for a 30 day supply.
- Duration of effect: Nuvigil is thought to have a longer duration of effect than Provigil. It is believed that Nuvigil “kicks-in” quicker (in 2 hours) compared to Provigil (in 2 to 4 hours) and produces an effect lasting up to 2 hours longer than Provigil.
- Generic availability: Provigil is sold as generic “modafinil,” but Nuvigil is not yet available as a generic.
- Half-life: The elimination half-life differs between the two drugs due to the fact that “S”-enantiomer in Provigil is cleared quicker than the “R”-enantiomer. Since Nuvigil doesn’t contain the “S”-enantiomer, its half-life is an estimated 15 hours compared to an estimated 12 hour half-life for Provigil.
- Ingredients: Provigil is comprised of a racemic mix of “S”-modafinil and “R”-modafinil whereas Nuvigil only contains “R”-modafinil.
- Popularity: Provigil remains the most popular drug compared to Nuvigil and other eugeroics.
Which drug is better? Nuvigil vs. Provigil.
Many people have attempted to determine whether Nuvigil is better than Provigil or vice-versa. From an efficacy standpoint, neither drug has been proven to be superior over the other. Some reports suggest that Nuvigil may possess less side effects than Provigil and be more potent in smaller doses. The fact that Nuvigil is considered a newer, updated formulation of Provigil has lead many people to conclude that it must be better.
Nuvigil is believed to have a quicker onset of action and longer duration of effect. Nuvigil also has four dosing increments (50 mg, 150 mg, 200 mg, 250 mg) and Provigil only has two dosing options (100 mg or 200 mg). While Nuvigil is hypothesized to be a more potent successor to Provigil, there’s no evidence to substantiate this hypothesis.
Which drug do you prefer: Nuvigil or Provigil?
If you’ve had the opportunity to try both Nuvigil and Provigil, be sure to share whether you prefer one over the other in the comments section below. Did you find Nuvigil to produce a quicker onset of action, have a longer duration of effect, or have less side effects than Provigil (or vice-versa)? Were the differences between the two drugs obvious to you or did they seem relatively similar in their effect?