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The Best Medications to Fight Fatigue

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Fatigue is a feeling of tiredness or exhaustion that is common after a hard day’s work. It can occur as a result of mentally challenging work, manual labor, or physical exercise. This is called post-exertional malaise. However, some people can feel fatigued without any physical or mental exercise. Such individuals may also complain of associated symptoms. A common symptom is a lack of energy, but there can also be poor motivation, sleep disorders, depression, and pain

If you feel tired all the time, it is important to be evaluated by a healthcare provider to identify the cause of your fatigue. Tiredness or fatigue can be a symptom of a wide range of medical conditions. Up to 4 out of 10 patients who see a doctor for fatigue are ultimately discovered to have undiagnosed but treatable health problems. Treating the medical condition can help reduce fatigue. However, if no underlying cause is found, there are treatment options to help relieve chronic fatigue.

Continue reading to learn more about fatigue and the different types of drugs used to treat it. 

What is chronic fatigue syndrome?

Nowadays, many people lead busy lives. Work and home responsibilities result in no time for relaxation and poor sleep habits. Consequently, many people feel constantly tired, run down, or worn out. 

But in some people, chronic fatigue cannot be explained by lifestyle alone. As mentioned, fatigue can be a symptom of various medical conditions, including extreme stress, obstructive sleep apnea, restless legs syndrome, irritable bowel syndrome, rheumatoid arthritis, heart disease, multiple sclerosis, or even something as common as a sore throat. 

A small number of individuals have a condition called chronic fatigue syndrome (CFS). Also known as myalgic encephalomyelitis (ME or ME/CFS) or systemic exertional intolerance disease (SEID), this complex disorder causes extreme fatigue. The fatigue lasts for a period of at least six months and cannot be explained by other causes. The tiredness is worse after physical or mental exertion but does not improve after resting. Other CFS symptoms can include unrefreshing sleep, dizziness when sitting upright from lying (orthostatic intolerance), and difficulties with memory and concentration.

The exact cause of chronic fatigue syndrome remains unknown, but experts believe it is triggered by a combination of psychological and physical factors. There is not a single test to diagnose chronic fatigue syndrome. Instead, doctors will usually perform a physical examination and run a battery of tests to rule out other health problems as potential causes before diagnosing CFS. Treatment consists of improving symptoms, whether it is to boost energy, reduce pain, improve sleep, or provide emotional support.

What medications are used to treat fatigue?

There is no cure for chronic fatigue syndrome. However, many over-the-counter and prescription medications, as well as alternative therapies, can help to ease the symptoms of this disorder. 

Every patient with chronic fatigue syndrome is different. The symptoms of CFS can vary significantly from person to person. A healthcare provider will usually tackle the worst symptoms first that are interfering with daily life. This could mean treatment of sleep disorders in one person, muscle aches in someone else, and memory problems in yet another person. Some of the medications used to treat chronic fatigue syndrome are described below.

Over-the-Counter Medications


Commonly known by its brand name, Tylenol, this medication can be used to ease headaches, muscle aches, and joint pain. Possible side effects include nausea, vomiting, rash, and liver damage at high doses. The safest maximum daily dose of Tylenol is 3,000 mg. Healthy individuals can take up to 4,000 mg per day. Exceeding 4,000 mg of acetaminophen daily can result in liver injury.  

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

This group of medicines can be used to relieve chronic fatigue syndrome symptoms like pain. Examples include ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox). Potential side effects are nausea, vomiting, heartburn, stomach ulcer, gastrointestinal bleeding, and kidney injury.


These medications (e.g., Benadryl, Sominex, Unisom) can be used temporarily as sleep aids. They can also help to relieve nausea. Side effects may include drowsiness, somnolence, lightheadedness, dry mouth, and a fast heart rate. 


Melatonin is a hormone the body produces naturally, which is involved in regulating the circadian rhythm responsible for sleeping and wakefulness patterns. It can help improve sleep quality and make you less tired during the day. It is also used to relieve jet lag and sleep problems due to shift work. Melatonin is generally effective and well-tolerated. Therefore, it is a good short-term solution for sleep problems. However,  there is limited information regarding the long-term use of melatonin.


L-Carnitine plays a vital role in energy production by transporting fatty acids into the cells. Some people benefit from supplements like L-carnitine for symptoms like fatigue, pain, and depression.

Prescription Drugs

Sleep Aids

A wide range of medications can be used to treat poor sleep in people with chronic fatigue syndrome. Getting a good night’s sleep can make you less tired during the day. Your doctor will first ensure you have good sleep habits. These include having a regular bedtime and sleeping in a quiet, dark, cool bedroom, in addition to limiting screen time before bedtime. Over-the-counter sleep aids may also be recommended to improve your sleep. 

If these measures don’t work, your doctor may prescribe prescription drugs like eszopiclone (Lunesta), zolpidem (Ambien), or ramelteon (Rozerem). Other options include certain types of antidepressants, benzodiazepines, and muscle relaxants, which are described below.

Like all prescription medications, these drugs can cause a wide range of side effects. You should work with your doctor to weigh the risks and benefits and explore other treatments as well.

Central Nervous System Stimulants 

Several drugs are stimulants, meaning they increase the activity of brain chemicals. Examples include modafinil (Provigil), armodafinil (Nuvigil), methamphetamine (Desoxyn), methylphenidate (Ritalin, Metadate), and amphetamine salts (Adderall). 

These medications can help relieve symptoms such as fatigue, daytime sleepiness, memory problems, and brain fog. Side effects of stimulants can include insomnia, high blood pressure, fast heart rate, headache, and loss of appetite.


Low doses of drugs like amitriptyline (Elavil), nortriptyline (Pamelor), trazodone (Desyrel), doxepin (Sinequan), and mirtazapine (Remeron) are used in chronic fatigue syndrome for their calming effects. However, these medicines can take 4-6 weeks to have an effect. Possible side effects include dry mouth, lightheadedness, fast heart rate, high blood pressure, and mild tremor.

Muscle Relaxants

Available under the brand name Flexeril, cyclobenzaprine is a muscle relaxant that may help symptoms like muscle spasms and pain. Potential side effects include drowsiness, dizziness, urination problems, leg swelling, and problems with short-term memory.

Antiseizure Drugs

Medications like gabapentin (Neurontin) and pregabalin (Lyrica) may be helpful with pain and restless leg syndrome. Common side effects include drowsiness, lightheadedness, and weight gain.


Benzodiazepines like clonazepam (Klonopin) and alprazolam (Xanax) promote sleep and relieve anxiety. This medicine can also help with muscle spasms and restless leg syndrome. Possible side effects include lightheadedness, drowsiness, slow reaction time, poor coordination, tolerance, and dependency when used for long periods.


Zolpidem (Ambien) is a sedative-hypnotic drug that eases sleep problems (it can help you fall asleep faster and stay asleep). Potential side effects include nausea, diarrhea, headache, daytime drowsiness, tolerance and dependency.


Promethazine (Phenergan) is used to relieve nausea and vomiting, though, it can also be helpful in easing restlessness. It can work as a sleep aid in people with chronic fatigue syndrome. Possible side effects include drowsiness, dry mouth, rash, hives, and problems with thinking clearly (especially for elderly people).

Pain Relievers

Doctors sometimes prescribe prescription pain medications if over-the-counter medications do not relieve pain symptoms in people with chronic fatigue syndrome. Some antidepressants may be used for this purpose. Opioid pain relievers, such as OxyContin, Vicodin, Fentanyl, and Tramadol, are rarely used because of their side effects, including a high risk of dependency and withdrawal.

What should I keep in mind while taking medications for fatigue?

Some of the considerations to keep in mind during treatment for chronic fatigue syndrome include:

  • Take your medications exactly as directed. Do not take a larger or smaller dose or take the medicine more or less frequently than prescribed.
  • Contact your doctor if the side effects are severe or do not go away.
  • Talk to your doctor before stopping any medication.
  • Do not use someone else’s prescription medication or share yours with others.
  • Give your doctor a complete list of your medications, including prescription medications, over-the-counter products, and herbal supplements to help avoid drug interactions.

What are some non-pharmacological treatments for chronic fatigue syndrome?

Before you start taking medications for chronic fatigue, you may want to try some easy solutions such as:

  • Practicing good sleep hygiene (going to bed and rising at the same time every day, getting at least 7-8 hours of sleep at night, avoiding alcohol and caffeine before bedtime).
  • Eating a healthy, balanced diet; drinking enough water to stay hydrated; and participating in a regular exercise program.
  • Reducing life stressors with meditation, deep breathing, yoga, tai chi, walking outdoors, reading a good book, listening to relaxing music, or joining support groups to deal with stress.


  1. https://www.cdc.gov/mmwr/volumes/65/wr/mm655051a4.htm
  2. https://www.mayoclinic.org/diseases-conditions/chronic-fatigue-syndrome/symptoms-causes/syc-20360490
  3. https://www.uspharmacist.com/article/fatigue-and-drowsiness-everyday-exhaustion-and-beyond