Might Your MS Medications Be Causing Sleep Problems?

A paper recently published in PLOS ONE suggests that some of the drugs people with MS might be using to treat pain—among them, gabapentinoids such as gabapentin and pregabilin— can lead to problems with sleep.

Gabapentin (brand name, Neurontin) is a popular medication taken by people with MS to treat neurological pain, such as trigeminal neuralgia or dysesthesia (burning sensations or pins and needles). It is also one of the first drugs commonly prescribed to treat spasms and spasticity.

Withdrawal effects

However, gabapentin has some side effects that might affect alertness, such as fatigue, dizziness, and excessive daytime sleepiness. It is also known to require tapering if one decides to stop taking this medication. If you suddenly stop taking it, your body will experience symptoms of withdrawal that could lead to significant sleep problems.

Lyrica (known generically as pregabilin) provides the same relief a gabapentin, but it too shares the same problems with side effects and concerns regarding withdrawal in users who decide to discontinue it.

Common drugs that can lead to sleep troubles

But these aren't the only medications that can have sleep problems as a side effect for something with MS. Problems can include either prevention or delay of sleep onset at bedtime (insomnia), restless sleep or sleep of poor quality, or excessive daytime sleepiness and cognitive "fog" while awake.

Both treatments specific to MS and medications that are taken to relieve MS symptoms can lead to sleep problems.

Disease-modifying therapies that might disrupt sleep

Aubagio (teriflunomide) can lead to trouble sleeping and headaches which might lead to insomnia (or, more specifically, "painsomnia").

Avonex (interferon beta 1a) can lead to restlessness, insomnia, and generally poor sleep quality.

Betaseron (interferon beta 1b) may cause insomnia in some users.

Copaxone(glatiramer acetate) has been shown to lead to overall poor sleep quality.

Extavia(interferon beta 1b) is known to cause insomnia in some users.

Lemtrada(alemtuzumab) can cause some sleeping issues a few days following infusion.

Plegridy(peginterferon beta 1a) may lead to extreme sleepiness that is the result of liver problems which can be a side effect of this medication.

Rebif(interferon beta 1a) can also lead to sleepiness related to liver problems.

Revia (Low-dose naltrexone) is known to lead to sleep disturbances in its users.

Tecfidera (dimethyl fumarate) is known to cause flushing, which can occur in the middle of the night and lead to a raging neurological itch that lasts for around 20 minutes. This medication can also cause diarrhea and irritable bowel symptoms that may intrude upon sleep.

Tysabri(natalizumab) has been shown to lead to overall poor sleep quality in its users.

Zinbryta(daclizumab) could lead to sleepiness that is related to depression, another side effect.

Symptoms and side effects of MS and their potential treatments

MS has a host of symptoms which might require drugs for relief:

  • anxiety and/or depression
  • frequency nighttime urination (nocturia)
  • muscular spasms
  • pain (neuropathic or musculoskeletal)
  • restless legs syndrome
  • sleep-disordered breathing (such as obstructive or central sleep apnea)
  • excessive daytime fatigue

Below are a number of medications that you might take for these problems which might also be the culprit behind any sleep problems you might be having.

Alertness medications

Taking a prescription for wakefulness may lead to a delay in sleep onset at night. This might seem obvious, but some people can take a drug like Provigil (modafinil) or Nuvigil (armodafinil) early in the morning (7am) in order to stay awake during the day and still experience its effects at 11pm that night.

Adderall, a stimulant medication (amphetamine and dextroamphetamine), is also well known for causing insomnia or restless sleep, but may be used to counteract extreme daytime fatigue.

Amantadine (Symmetrel) is an antiviral medication that can help with daytime fatigue, but be aware: if taken too late in the day, it can disrupt nighttime sleep.

If sleeplessness is a recurring problem with these kinds of medications, a discussion with the prescribing physician might be in order, as reduced dosages might still be effective for those who are sensitive to them.


These medications (mostly diphenhydramine, which is found in Benadryl) are typically not recommended for people with MS because they can disrupt memory and learning.

However, those taking certain disease-modifying therapies may experience a distinct "flushing" side effect. In some cases, a physician may suggest the use of Benadryl to counteract the intense itching that might accompany flushing. Ask your doctor or pharmacist for other options for managing this side effect.


Many MS patients are given corticosteroids for MS relapses, either in intravenous (Solu-Medrol, methylprednisolone) or oral form (Deltasone, prednisone), over a period of three to seven days.

Common side effects for either steroid treatment are insomnia at night and excessive daytime sleepiness.

The good news? These side effects are temporary and resolve once the steroid therapy is concluded.

Drugs for depression

If you're taking an SSRI or SSNRI medication (such as Prozac [fluoxetine] or duloxetine hydrochloride (Cymbalta]), you may experience insomnia, sleepwalking, or vivid, nightmarish dreams.

Other antidepressants that can cause sleep disruption and restlessness include buproprion (Wellbutrin)

Tricyclic antidepressants such as Pamelor (nortiptyline) are used to treat pain but can cause excessive daytime sleepiness.

Trazodone (Desyrel) is a tetracyclic antidepressant that can cause sleeping problems but is also well known to lead to excessive sleepiness when used in combination with sleep aids.

Sleep aids

Sleep aids are meant to help sleep, right? Unfortunately, they can also lead to unusual sleep behaviors and problems with headaches and fatigue the next day.

Ambien (zolpidem) may be an effective sleep aid, but it can lead to unusual nighttime behaviors as well as feelings of hangover and cognitive fog the day after use, as well as problems driving or operating machinery.

Other benzodiazepine sleep aids such as Xanax (alprazolam), Librium (chlordiazepoxide), Valium (diazepam), and Ativan (lorazepam) are meant to be taken in the short term, and a period of tapering is often required to prevent developing a tolerance or addiction to them.

Tolerance or addiction means the body will become habituated to them in the system and will respond in withdrawal when they are no longer present. Drug withdrawals usually cause serious sleep problems.

Melatonin may be generally recognized as safe (GRAS), but it is also known to lead to nightmares and bizarre dream content for some who take it.

Don't forget: Not everything is caused by MS (or drugs)

Sleep disorders can happen independently of MS or medication use. Many, like circadian rhythm sleep disorders, sleep apnea, insomnia, or periodic limb movements of sleep, can be hidden problems that only come to light when a person complains about having trouble sleeping at night or staying awake during the day.

The best way to identify and diagnose a sleep disorder is to consult your physician and have a sleep study. Fortunately, all sleep disorders can (and should) be treated. Treating a sleep problem can reduce pain sensitivity, lessen fatigue, and improve mood, among other things.

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