Modafinil (brand name Provigil) is one of the primary drugs used to manage narcolepsy. Narcolepsy is a rare condition that affects sleep control and results in daytime sleepiness, often sudden and uncontrollable.

The public’s interest in Modafinil comes from the drug’s association with a class of medicines called ‘smart drugs,’ also called nootropics and cognitive enhancers. Many individuals search for cognitive enhancement drugs, and Modafinil is one of the primary drugs that always gets mentioned.

Today, We will review modafinil alternatives, drugs that promote awareness and improve cognitive functions. We will not check over-the-counter modafinil alternatives or Modafinil’s natural alternatives simply because none of the existing supplements or over-the-counter products have the same effect as Modafinil.

What Is Modafinil?

Modafinil is classified as a prescription-only medication in the USA. A doctor or another qualified prescriber can only prescribe POMs. Modafinil has narrow licensed use. It is used to manage excessive sleepiness in adults associated with narcolepsy with or without cataplexy (sudden muscle weakness).

The second licensed use of Modafinil covers individuals who experience excessive sleepiness, defined as difficulty keeping wakefulness and an increased likelihood of falling asleep in inappropriate situations (eMC, 2020).

Well-defined licensed use for Modafinil means that a doctor would only prescribe it to treat narcolepsy after an appropriate referral is made to a specialist.

Is Modafinil A Smart Drug?

The mechanism of action of Modafinil is not fully understood. Modafinil increases wakefulness and can be a cognitive-enhancing drug (‘smart drug’). When studied in patients with excessive sleepiness, Modafinil significantly affected wakefulness (Hirshkowitz & Black, 2007).

The available evidence shows a small capability for Modafinil to be a cognitive enhancer in people who do not have a sleeping disorder (Kredlow et al., 2019). Based on current evidence, Modafinil may produce ‘modest’ benefits in terms of cognitive enhancement.

Individuals who perform poorest (those with lower IQ) may benefit more significantly. Improvement in this group of people may be more effective. Taking ‘smart drugs’ in people with a modest level of cognitive function may lead to overconfidence (Nicholson, 2015).

A systemic review on modafinil use by youths aged 12-25 suggests that Modafinil improves reaction time, problem-solving, and logical reasoning (Bagot & Kaminer, 2014).

The wake-promoting properties of Modafinil are well known. Although the mechanism underlying the wake-promoting action is fully understood, this effect is similar to other drugs, for example, amphetamines and methylphenidate, but with a distinct pharmacological profile (FDA, 2010).

When studied in animals, Modafinil produced psychoactive and euphoric effects and changes in mood, thinking, and awareness, all of which are associated with reactions produced by stimulants in people (ibid).

Is Modafinil Addictive?

Studies on Modafinil in people indicate that Modafinil is less likely to be abused than other ‘stimulating’ drugs, for example, methylphenidate or dexamphetamine (McClellan KJ & Spencer, 1998). Additionally, compared with alternative medications such as amphetamines, Modafinil is considered safe with a small number (‘minimal’) of side effects (Easow et al., 2013).

Modafinil Alternatives Drugs

Various drugs can be used to manage narcolepsy, though most require off-label use. Take a look at the alternatives to Modafinil.

  • Pitolisant
  • Armodafinil
  • Atomoxetine
  • Methylphenidate
  • Amfetamines
  • Sodium Oxybate

1. Pitolisant: Modafinil Alternative Drug To Treat Narcolepsy

Pitolisant (brand name: Wakix) is the latest drug licensed for narcolepsy. Pitolisant is a prescription-only medication. Treatment with pitolisant is usually initiated by a doctor specializing in treating sleeping disorders.

Pitolisant is an exceptionally rarely prescribed drug. A quick search on shows that Pitolisant was named less than 300 times in the last 12 months (, 2021).

The main reason is the drug cost, which is £310 for a 30-day treatment with a lower dose of pitolisant and £620 for a treatment with a higher pitolisant amount (prices as of February 2017, excluding VAT).

Pitolisant Vs. Modafinil: What’s The Difference?

Pitolisant is described as a ‘first in class drug. Pitolisan’s mechanism of action is different from Modafinil. Pitolisant acts primarily on histamine receptors in the brain, possibly affecting noradrenaline (same as Modafinil) and dopamine, resulting in increased wakefulness.

Histamine neurons also control various functions, including memory and attention (Romigi et al., 2018).

When studied in animals, pitolisant was found not to cause dependence or induce ‘abuse’ behavior. Pitolisant enhanced memory performance in animals (ibid).

2. Armodafinil

Armodafinil is closely related to Modafinil. Modafinil is a 50:50 mixture of two enantiomers, a combination of 50% to 50% of two molecules that are mirror images of each other. In a simple context, you could represent enantiomers with your left and right hand; both look the same and mirror each other.

In pharmaceuticals, it is possible to market enantiomers as separate drugs. Common prescription drugs that exist as mirror images of each other are esomeprazole and omeprazole (see Esomeprazole vs. Omeprazole post). Armodafinil is not available but is used to treat narcolepsy in many countries.

You also like to read Armodafinil vs. Modafinil – Which Works Best for You?

3. Atomoxetine

Atomoxetine (brand name: Strattera) is the first drug on the list of modafinil alternatives, mainly used Strattera for treating Attention Deficit Hyperactivity Disorder (ADHD) in children and adults. Atomoxetine is a prescription-only medication. Atomoxetine is available as a generic drug (atomoxetine hydrochloride) and branded as Strattera.

Is atomoxetine a cognitive enhancer?

Atomoxetine is a non-stimulant drug that primarily affects one neurotransmitter called norepinephrine (noradrenaline) in the brain. Atomoxetine stops the action of the norepinephrine transporter in the brain and, therefore, increases the concentration (amount) of norepinephrine in the brain. Noradrenaline regulates cognitive function, attention, and stress reactions (Hussain et al., 2020).

Unlike other drugs discussed in the following paragraphs, atomoxetine does not affect dopamine actions in the brain’s relevant parts associated with pleasure. Therefore, atomoxetine is classified as a non-addictive medication with a low tendency for abuse.

There are a large number of research papers on atomoxetine. When used to treat ADHD, atomoxetine significantly improves visual memory and attention (Shang & Gau, 2012).

Furthermore, atomoxetine enhanced many parts of ‘ executive function’ such as cognitive flexibility, short-term/working memory, attention, and susceptibility to distraction in young adults. Other evidence suggests that atomoxetine may boost other aspects of cognition beyond engagement (Callahan, 2019).

4. Modafinil Alternatives: Methylphenidate

Methylphenidate is a prescription-only drug available to treat ADHD. Methylphenidate is classified as a controlled drug (Schedule 2), bringing additional legal requirements for writing prescriptions and various medicine supply restrictions. Methylphenidate would only be prescribed for ADHD by a doctor specializing in behavioral disorders.

Methylphenidate: legal aspects

Despite its classification as a prescription-only, controlled drug, purchasing methylphenidate is possible from overseas pharmacies. Unlike Modafinil, possessing a class B controlled drug (not prescribed by a doctor) carries imprisonment and fine penalties.

Methylphenidate is available in many forms. Methylphenidate is broadly available in immediate-release forms, including generic and controlled-release (prolonged release / modified release) tablets and capsules.

Common brands of methylphenidate prescribed:

  • Concerta XL prolonged-release tablets
  • Equasym modified-release capsules
  • Medikinet tablets (immediate-release)
  • Medikinet XL prolonged-release capsules
  • Ritalin immediate-release tablets
  • Ritalin XL modified-release capsules
  • Xaggitin prolonged-release tablets

Is methylphenidate a ‘smart drug’?

Methylphenidate became a popular choice as a cognitive enhancer by healthy individuals seeking to improve their concentration, stay awake longer to study, and increase motivation functioning (Batistela et al., 2016). It is known, for example, that medical students take cognitive enhancement drugs, including methylphenidate (Lane et al., 2015).

There is no consistent evidence that methylphenidate improves cognitive enhancement, although some evidence on memory has been demonstrated in laboratory tests (Nicholson & Wilson, 2017).

Like Modafinil, individuals with intellectual processes are ‘below optimal level’ (Batistela et al., 2016).

Related Blog: Modafinil for students

Methylphenidate vs. Modafinil

Methylphenidate has a mechanism of action distinct from Modafinil. Methylphenidate is classified as a stimulant, primarily affecting the release and increasing dopamine in the brain.

The end effect of increased dopamine in the brain is similar to one produced by cocaine and amphetamines (not to the same extent), yet the mechanism of action is different (Morton & Stockton, 2000).

Methylphenidate is classified as a stimulant drug, making it a reasonable option for treating narcolepsy. Methylphenidate is not licensed to treat narcolepsy; therefore, other medications like Modafinil would be considered in the first instance.

5. Amfetamines

Two amfetamines are used dexamfetamine and lisdexamfetamine. Dexamfetamine is licensed for managing narcolepsy and ADHD, whereas lisdexamfetamine is just for ADHD.

Both drugs are prescription-only medicines, classified as controlled drugs Schedule 2 (class B). Both drugs need to be initiated by a specialist, i.e., a doctor is in secondary care rather than a doctor.

Amfetamines positively impact cognitive functioning, as demonstrated by some studies. For example, when investigated in school-aged children, amfetamines improved attention and performance and decreased the number of errors (Rapoport et al., 1978).

Additionally, amfetamines may enhance the attainment of new knowledge and how it is stored in the brain and retrieved information (Bagot & Kaminer, 2014).

The positive effects of amfetamines on cognitive functioning are overshadowed by negative aspects of the treatment, including psycho-stimulation, which may be characterized by individuals having ‘high,’ potential ‘high’ addictive properties, which all together increases the chances of the abuse.

6. Sodium Oxybate As Modafinil Alternative

Sodium oxybate is a prescription-only medication licensed for narcolepsy but rarely prescribed in practice. Sodium oxybate is a controlled drug Schedule 2 (class B).

Sodium oxybate comes only in liquid form as a generic medication or branded as a Xyrem oral solution. One of the main drivers for the low popularity of this drug in the treatment of narcolepsy is its price, which stands at £360 per 180ml of oral solution.

Sodium oxybate (GHB) is widely used as an illegal drug. The exact mechanism of sodium oxybate is unknown, but it is believed that sodium oxybate improves sleep at night, which promotes improved alertness the following day (Kothare & Kaleyias, 2010).

The use of sodium oxybate by sleep-deprived, healthy volunteers demonstrated that this drug improves daytime alertness and attention (Walsh et al., 2010).

How do you switch to a Modafinil alternative?

Are you considering a switch to a Modafinil alternative? It’s essential to consult your healthcare provider before making any changes. Modafinil is a widely used medication for enhancing alertness and focus, so abruptly discontinuing it isn’t advisable. Seek medical advice to discuss your reasons for switching. Common motivations include reducing side effects or exploring natural alternatives.

Your physician will help you evaluate your options, considering your willingness to try different treatments, potential side effects, and your current needs. Switching may involve dose adjustments and some trial and error. Be patient; finding a suitable alternative that suits your needs and lifestyle may take time.

Final Words From Druggist

We reviewed the main prescription-only drugs, classified as modafinil alternatives. All medicines have some evidence of cognitive enhancement and, most importantly, evidence of being effective in treating narcolepsy due to its significant effect on wakefulness.

We did not cover two fundamental aspects of drug use that We did not cover in this post: potential side effects and interactions with other drugs. Individuals considering using drugs to improve cognition must recognize the risk of treatment (side effects) and possible interaction with other medicines they may take.

The legal route of modafinil alternatives/cognitive enhancers is through a consultation with a doctor (and a specialist), almost eliminating unlicensed use of the above medicines as cognitive enhancers in healthy individuals. Purchasing drugs from the Internet carries the additional risk of medication not being genuine with questionable quality.

Disclaimer: Please see your healthcare practitioner for any medical queries or concerns. Peer-reviewed research and information from medical societies and government agencies are used to support the articles in Health Guide. They are not, however, a replacement for expert medical advice, diagnosis, or treatment.

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