Excessive sleepiness is a symptom of conditions, such as narcolepsy, idiopathic hypersomnia and obstructive sleep apnea, in which sleep in an inappropriate setting or episodes of unintentional sleep occurs. In mild cases, people fall asleep while sitting quietly or reading a book (for example). The most serious cases of excessive sleepiness involve real danger, such as falling asleep while driving.
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Causes of excessive sleepiness include:
- certain medications
- rheumatologic/endocrinologic disorders (e.g., diabetes, hypothyroidism)
- neurlogic disorders (e.g., strokes, tumors, head trauma, demyelinating diseases)
- heart, kidney or liver failure
Currently, sleep medicine offers several type of drugs for the treatment of excessive sleepiness. Of course, treating the underlying cause of the symptom would theoretically be a better approach, but that’s not always possible. (A sleep specialist would be able to tell you whether or not it’s possible in your case.) Remember, while stimulants promote wakefulness, they cannot substitute for sleep; you should always try to obtain sufficient sleep whenever possible.
Following is the list of medications commonly used for excessive daytime sleepiness:
Stimulants are used to treat the symptom of excessive daytime sleepiness which occurs in narcolepsy and idiopathic hypersomnia. The main problem with this class of medications is their high abuse and dependency potential.
The “original” stimulant was cocaine, a substance made from the coca plant. However, it could not be used in medicine because of its high abuse and addiction potential.
The first stimulant used to treat narcolepsy was ephedrine, however it was expensive and had awful side effects.
Amphetamine and Methamphetamine
Amphetamine (e.g., Adderall, Vyvance, Dexedrine, Benzedrine) and methamphetamine (e.g., Desoxyn, Methadrine) increase energy, elevate mood, prevent fatigue, increase vigilance and prevent sleep. They are also safer (and cheaper) than ephedrine.
Peak levels are achieved about 30 minutes-8 hours after ingesting the medicine and last anywhere between 4 and 34 hours, depending on the preparation.
When the effect wears down, tiredness, sleepiness, lethargy, listlessness and mild depression may occur.
Side effects include: Irritability, mood changes, headaches, palpitations, tremors, excessive sweating, insomnia, delusions, hallucinations, increased blood pressure, dizziness, flushing, pallor, muscular pains/jerking, tachycardia, cardiac arrhythmias, painful urination, gastrointestinal disturbance/discomfort, anorexia, dryness of the mouth, restlessness, agitation, confusion, dysphoria, apprehension, delirium, nausea, talkativeness, orofacial dyskinesia (tics), nervousness and chorea.
Perhaps the biggest problem with amphetamine and methamphetamine is that they are toxic to the nervous system. Adding antioxidants or L-carnitine may be helpful in preventing damage.
Metyhlphenidate (Ritalin), a derivative of amphetamine, has an immediate effect (1-4 hours after ingestion) and a shorter duration of action (4 hours; thus often taken 2-4 times daily).
There are also sustained-release methylphenidate preparations, such as Concerta, which can last up to 16 hours.
Side effects: Same as amphetamines besides less reduction of appetite and increased blood pressure; nervousness, insomnia, increased heart rate.
An overdose may lead to seizures, dysrhythmias and hyperthermia.
Tolerance is common during long-term use of amphetamine, methamphetamine and methylphenidate, especially at higher doses, and there is a risk of addiction and abuse. Fortunately, there may be better alternatives, which I cover below.
Keep in mind though that if you decide to stop using amphetamines, do so gradually, otherwise you may suffer from prolonged bouts of recovery sleep, disrupted sleep, vivid or unpleasant dreams, depression and a worsening of daytime sleepiness.
A milder stimulant with slower onset of action, Pemoline was discontinued in several countries, including the US, due to the liver toxicity it sometimes causes.
Producing a relatively weak central nervous system stimulation, a reduction in appetite and an increase in alertness with little or no effect on mood or the cardiovascular system, Mazindol is an effective dopamine and norepinephrine uptake inhibitor used for the treatment of both EDS and cataplexy.
It has a low abuse potential, however it causes significant side effects, such as irritability, headaches, anorexia, gastrointestinal symptoms, insomnia, nervousness, dry mouth, nausea, constipation, urinary retention, angioneurotic edema, vomiting and tremor, which is why it is rarely used in the United States.
May be useful for the treatment of excessive sleepiness associated with narcolepsy, especially in cases associated with depression. Side effects include risk for seizures.
Atomoxetine and Reboxetine
Atomoxetine (Strattera) and reboxetine are slightly wake promoting, anticataplectic and reduce REM sleep and with no risk for abuse. These drugs may be helpful in some cases of narcolepsy and idiopathic hypersomnia.
Side effects include: Increased heart rate, tachycardia, hypertension and blood pressure and sexual dysfunction.
The oldest and to this day the most popular wake-promoting agent is caffeine, which is a moderately effective alerting agent when it’s not used regularly (due to tolerance).
Caffeine’s main effect is to make it more difficult to fall asleep and maintain sleep. Takes between 30 minutes to 2 hours to reach full effect. Caffeine improves alertness, mood and cognitive performance, and reduces subjective sleepiness and sleep inertia.
Since caffeine can be used without prescription (even in the form of tablets), it can be used by patients with narcolepsy before they get a formal diagnosis.
Duration of caffeine’s effect on alertness
- 1 cup of coffee (75-150 mg caffeine) – up to 90 minutes
- 2 cups of coffee (200 mg caffeine) – up to 4 hours
- 3-4 cups of coffee (300-400 mg caffeine) – 5-8 hours
Caffeine can be used when the sleepiness is not interfering with one’s life or endangering it. Besides its ineffectiveness in cases such as narcolepsy and hypersomnia, there are some problems with caffeine:
- It’s difficult to get a large enough dose (unless taking caffeine pills.)
- Caffeine’s effect is short lived.
- Tolerance – using caffeine regularly decreases its effectiveness in maintaining alertness.
- Withdrawal from caffeine is not easy and involves cravings and symptoms such as headaches, sleepiness, fatigue, fogginess, difficulty concentrating and depressed mood.
- Taken within 6 hours of bedtime, caffeine postpones sleep onset and reduces the amount of slow wave sleep, the sleep efficiency and total sleep time.
- Side effects of caffeine include palpitations, hypertension, increased mental alertness, a faster and clearer flow of thought, wakefulness, restlessness, increased gastric acid secretion and increased urine output. Heavy consumption (12 or more cups per day/1.5 g caffeine) causes agitation, anxiety, tremors, rapid breading and insomnia
Modafinil (Provigil) and Armodafinil (Nuvigil) are used for the treatment of narcolepsy, idiopathic hypersomnia and periodic hypersomnia (Klein-Levin syndrome), shift work sleep disorder and obstructive sleep apnea.
Benefits of somnolytics over stimulants
- Fewer side effects, specifically they do not affect blood pressure, cortisol, melatonin and growth hormone levels, or cause tachycardia, irritability and agitation.
- Modafinil and Armodafinil also have a lower “street value” and abuse potential.
- Very low occurrence of tolerance.
- Finally, they do not cause withdrawal symptoms, such as rebound hypersomnolence, after stopping the medication.
The effect of either medication peaks 2-4 hours after ingestion, and lasts 4-15 hours.
Armodafinil’s effect may last longer, and may therefore be better when one dose of Modafinil is not enough to last for the entire day.
Side effects: Headaches, nausea, anxiety, insomnia, rarely psychosis and severe systemic rash (e.g., Stevens-Johnson syndrome). Side effects often go away with continued use.
While modafinil is currently regarded as the best treatment for excessive daytime sleepiness in Narcolepsy, it has several problems:
- It doesn’t work well for cataplexy and other symptoms of abnormal REM sleep.
- In hepatic and renal insufficiency cases, a lower dose should be taken.
- Decreases the efficacy of steroidal contraceptives and effect lasts for a month after discontinuing. If your taking low-estrogen contraception, you should probably ask your doctor for an alternative.
- A study published on October 2018 raises concerns about clastogenic/mutagenic properties of the drug. In simpler terms, this means that modafinil, even in the standard dose, may alter/destroy DNA. To put things in perspective, the study was done on rats. However, rats have a similar metabolism as humans, and so, the writers conclude, “the data in the present study is worrying […] there should be greater caution as to the use of this psychostimulant by human beings, especially when taken without prescription.”
Sodium oxybate (Xyrem), the sodium salt of GHB (the “date rape drug”), is used to treat cataplexy and excessive sleepiness in narcolepsy. It’s a mild stimulant and a wake-promoting agent, which gradually improves wakefulness over months of regular use.
It’s taken at bedtime and again 2.5-4 hours into sleep.
Onset of action is 15-30 minutes when taken orally and the effect lasts 30-60 minutes.
When using sodium oxybate, it’s best to eat the last meal of the day several hours (at least 2-4 hours) before bedtime since food (especially high-fat foods) can interfere with absorption of the drug. Alcohol should not be combined with this medication. Allow at least 6 hours between taking this drug and driving or operating machinery.
For some patients sodium oxybate is prescribed in addition to modafinil, especially when there’s a problem of inadvertent naps and sleep attacks.
Side effects: nausea, insomnia, headache, dizziness, vomiting, dyspepsia, abdominal pain, incontinence, somnolence, enuresis, sleepwalking, depression, suicidal ideation, confusion, psychosis and amnesic sleep eating/driving and respiratory suppression.
Sodium oxybate is not recommended if you
- have succinic semialdehyde dehydrogenase deficiency.
- are treated with sedative hypnotic agents or other CNS depressants.
- are obese or have OSA (Obstructive Sleep Apnea).
- have congestive heart failure, chronic renal failure or high blood pressure (hypertension).
There are several problems with sodium oxybate, including risk of respiratory depression and death with overdose and very long response time (2 months and more). Because of its ability to induce euphoria and craving, using sodium oxybate entails the risk of dependence and abuse.
Ritanserin is another drug which may cause some improvement in daytime sleepiness in narcoleptics. Its onset of action is 140 minutes and the effect lasts for 40 hours. The most common side effect is constipation.
Selegiline (L-Desprenyl) is a MAO inhibiting methamphetamine derivative which may be useful for treating sleepiness, improving alertness and mood and reducing cataplexy (There is very few data to support use of selegiline for daytime sleepiness.)
Onset of action: 40-90 minutes.
Duration of effect: 10 hours.
It has a low abuse potential and has relatively few side effects compared to amphetamines.
Side effects: Decreased systolic arterial pressure, orthostatic hypotension, weight loss, diarrhea, indigestion, headache, insomnia, xerostomia, hypertensive crisis, suicidal thoughts (especially in children, adolescents and young adults with major psychiatric disorders.)
Solriamfetol by Jazz Pharmaceuticals is a drug used since March 2018 (when it was approved by the FDA) for the treatment of excessive sleepiness.
Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI), meaning it works by increasing the amount of the neurotransmitters norepinephrine and dopamine in the certain areas of the brain.
A review of the new drug published in the Expert Review of Respiratory Medicine concluded that solriamfetol “is well tolerated and effective in reducing sleepiness and is an alternative to modafinil or armodafinil. Unlike stimulants like methylphenidate or dextroamphetamine, it does not have cardiac effects, rebound hypersomnia, or withdrawal effects.”
It was shown to be helpful in excessive daytime sleepiness associated with obstructive sleep apnea.
Recently, a randomized, double-blind, placebo-controlled, crossover study published in the Journal of Psychopharmacology in October 2018 found solriamfetol has an abuse potential. Therefore, if your doctor prescribes it for you, make sure to let her know in case you have a history of drug abuse.
In the same study, side effects of the drug included hypervigilance, elevated mood, dry mouth, excessive sweating and insomnia.
Additional adverse events may include headache, nausea and dizziness.
Conclusion: Drugs for Excessive Daytime Sleepiness
When possible you should consult with a sleep specialist to see if it’s possible to treat the cause of excessive day time sleepiness instead of the symptom. Using sleep promoting agents carries a high potential for misuse and abuse.
Unfortunately, many disorders, including narcolepsy, hypersomnia, SWSD, OSA, currently have no cure, and when they entail immense tiredness during the day to the degree that day to day functioning is compromised, then medications can be tried to alleviate the excessive daytime sleepiness symptom.
It’s important to get a diagnosis from a sleep doctor before taking any alerting medications because it’s essential to know which drug would help the most and cause the least amount of damage for every situation.
Several factors will determine which medication you are prescribed, including how long it takes for the effect to start, how long the effect lasts, the tolerance, side effects and risk for abuse.
In general, patients begin with compounds that inhibit dopamine reuptake first (modafinil, methylphenidate) and then move on to the use of dopamine-releasing agents (e.g., amphetamines) only if the other compounds are not effective enough. In some cases, different medications will be combined.
Modafinil and armodafinil are first-line agents and will be recommended for most people by sleep physicians as they have few side effects. Only when they are not effective should second-line agents may be used keeping in mind their abuse risk, tolerance issues and side effects. Caffeine may help in mild cases. Sodium oxybate is used for patients with narcolepsy and cataplexy.
In any case, alerting medications should just be a part of a comprehensive therapeutic approach to excessive somnolence, in addition to sleep hygiene and assessment and addressing of lifestyle factors contributing to the problem. Short naps (20-30 minutes) following ingestion of caffeine, for example, can be incorporated by some patients.
A sleep consultant can help educate and refer you to information about your condition as well as clarify the goals of treatment, side effects, risks and benefits.
When using wake promoting medications, your doctor should follow-up with you often and measure your weight, pulse and blood pressure to determine the effective dose at least every 6-12 months.
I’m sorry to hear your daughter suffers from EDS and that you were diagnosed with NL.
NL diagnosis requires a sleep study to rule out other causes of EDS, such as too little sleep and poor quality sleep, followed by an MSLT. REM-suppressing medications, such as Prozac and Wellbutrin, should be stopped at least two weeks beforehand, ideally one month or more. Caffeine and nicotine should be avoided on the day of the test and in sensitive individuals perhaps also on the day before.
Therefore, I would suggest to go through another sleep study and MSLT, if possible. There are also other tests you can discuss with your doctor, such as measuring CSF hypocretin levels.
Until then if you suspect your daughter is suffering from NL, I’d recommend being extra careful with sleep hygiene, avoiding sleep deprivation, and nap planning throughout the day.
If needed, I am happy to provide additional support and guidance via my consultation services, see: https://dreammerchant.shop/.
My 19-year-old daughter has excessive daytime sleepiness. She sleeps over 11 hours per day, takes naps and wakes up and refreshed, has difficulty concentrating on schoolwork because of fatigue. I was just diagnosed with a narcolepsy diagnosis. She also had a sleep study but her MLST latency was 16.47. She had a bout of major depression about three years ago and has been taking 40 mg of Prozac and 150 mg of Wellbutrin. The sleep study was scheduled and she only had nine days off of her depression medicine before her sleep study. She did not get a narcolepsy diagnosis, but she is really struggling with sleep. Since she has been home from college this summer, she barely sees anyone and has not been involved in any activities. She says she is not depressed, but always tired. My grandmother also was probably narcoleptic. My question is since the sleep study was only nine days after her stopping prozac, could that have skewed the results. I read that process has a long half-life and the test should have been taken after six weeks. She’s really struggling, do you have any suggestions for me to help her