Medicine for Fatigue:What Works and Why

There's no cure for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sometimes called systemic exertion intolerance disease (SEID). Also, there are no FDA-approved medications to treat it. But some over-the-counter and prescription medications may help ease your symptoms.

Your symptoms may differ from those of someone else. That’s because ME/CFS varies from person to person. While fatigue and muscle pain might be your worst issues, constantly waking up unrested and having memory loss might be the biggest problems for someone else.

You and your doctor should try to tackle your toughest symptoms first — the ones that interfere most with your daily life.

CFS Medications for Sleep Problems

Many people with ME/CFS have some kind of sleep disorder. Getting a good (or at least better) night’s sleep could help you feel less tired during the day.

First, your doctor will make sure you have good sleep habits. These include sticking to a regular bedtime and wake time and keeping your bedroom quiet, dark, and cool.

If this doesn’t improve your sleep, they might suggest an over-the-counter sleep aid, such as an antihistamine. While these can help you sleep well through the night, the downside is that the effects can last more than eight hours. This means you could feel drowsy throughout the day, which is exactly what you’re trying to avoid. But not all sleep aids affect everyone in the same way. Talk to your doctor about which type would be best for you and how to take it.

If over-the-counter sleeping pills don’t work, your doctor might suggest a prescription sleeping pill. These drugs aim to get your sleep on track at the lowest possible dose in the shortest amount of time. You aren’t supposed to take them long-term.

Some prescription sleep medications help you get to sleep, such as:

  • Eszopiclone (Lunesta)
  • Ramelteon (Rozerem)
  • Zaleplon (Sonata)
  • Zolpidem (Ambien , Edluar, Intermezzo, Zolpimist)

Other meds that your doctor may prescribe can help you fall asleep or stay asleep. For example:

  • Amitriptyline
  • Benzodiazepines
  • Doxepin
  • Dual orexin receptor antagonists (DORA), including daridorexant (QUVIVIQ), lemborexant (Dayvigo), and suvorexant (Belsomra)
  • Other a ntidepressants
  • Trazodone (Oleptro)

All prescription sleep medications cause side effects. Some of these side effects, such as daytime sleepiness, dizziness, unsteadiness, and memory lapse, are also symptoms of ME/CFS. You and your doctor should weigh the pros and cons. The beneficial effects of many of these medicines wear off in a few weeks, making them unsuitable for long-term treatment.

Stimulants for CFS

For some people, doctors prescribe stimulants, such as the ones used to treat ADHD. These medicines help ease fatigue and problems with memory and concentration. But it can be risky to use them for chronic fatigue syndrome. They may give you energy and focus, which could cause you to get stuck in a cycle of overdoing it and then “crashing.” That would worsen your condition. Some of these stimulants can also be addictive.

Since people with ME/CFS are very sensitive to any medicines that affect the brain, some may feel irritated and agitated after taking stimulants in standard doses. They should be prescribed in low doses by doctors who often prescribe them and know how to handle the side effects.

If you and your doctor decide to try a stimulant, there are many to choose from. They will help you pick the best one for you.

Chronic Fatigue Syndrome Medications for Pain

Pain often goes hand in hand with ME/CFS. Up to 59% of people with CFS report having headaches, for example. If ME/CFS gives you headaches, migraines, or muscle and joint pain, your doctor might give you prescription medications or over-the-counter pain relievers, such as acetaminophen, aspirin, or ibuprofen .

If the first medications your doctor suggests don’t ease your pain, they might prescribe stronger ones or medications such as tricyclic antidepressants, which often help chronic pain. Or they may refer you to a pain specialist.

Chronic Fatigue Syndrome Medications for Orthostatic Intolerance

Orthostatic intolerance is a condition where you have certain symptoms when you stand up. Those may include dizziness, lightheadedness, fainting, or a rapid increase in your heart rate. If you have ME/CFS, you might experience these symptoms. Some prescription drugs that might help are:

  • Fludrocortisone (Florinef)
  • Midodrine 
  • Propranolol XL (Inderal, InnoPran XL)

Talk to your doctor if you have these symptoms.

Antidepressants for Chronic Fatigue Syndrome

About half of people with ME/CFS develop depression at some point. If you and your doctor decide an antidepressant is right for you, work together to choose one that’s least likely to cause side effects that could worsen your chronic fatigue syndrome.

There are several types of antidepressants, including:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Atypical antidepressants
  • Monoamine oxidase inhibitors (MAOIs)
  • Tricyclic antidepressants (TCAs)
  • N-methyl-D-aspartate (NMDA) antagonists

Your doctor may also advise you to see a mental health counselor for talk therapy. Also known as psychotherapy, talk therapy includes different therapeutic approaches such as cognitive behavioral therapy (CBT), interpersonal therapy (IPT), psychodynamic therapy, and humanistic therapy. Each has a different way of addressing your thoughts, behaviors, relationships, and underlying issues. The best one for you depends on your issues, history, and circumstances.

Experimental Chronic Fatigue Syndrome Medications

Researchers are looking into medications that might help manage your symptoms of ME/CFS. Some experimental medications that have been studied are Ampligen, low-dose naltrexone (LDN), and rituximab. Studies are also looking into whether antivirals, neuromodulators, PDE5 inhibitors, and other approaches could help ease your ME/CFS discomfort.