Doctors may prescribe off-label medications such as amitriptyline, topiramate, or ondansetron to help treat concussion symptoms like headaches, sleep problems, and nausea.

A concussion is a mild traumatic brain injury (mTBI). Treatment often focuses on rest and symptom relief, but it must always be managed by a healthcare professional.

Currently, the FDA hasn’t approved any medications to treat concussions. Doctors may prescribe off-label options to ease symptoms such as headaches and sleep disturbances.

Below are 10 medications doctors may prescribe to treat concussion symptoms.

Acetaminophen (Tylenol) is an over-the-counter (OTC) pain medication that helps relieve mild to moderate pain and fever.

Research shows doctors often prefer it in the first days after a concussion, since aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can increase bleeding risk.

Another 2023 study found that acetaminophen is often the first choice for post-concussion headaches, providing short-term relief.

However, the same study also showed it doesn’t prevent headaches from lasting more than the first week, and its long-term benefit is still not clear.

The typical adult dose is 325 to 1,000 milligrams (mg) every 4 to 6 hours as needed, not exceeding 4,000 mg per day. Always check with your doctor for the safest dosing.

Acetaminophen may cause severe liver damage at high doses, especially when combined with alcohol or other products that contain acetaminophen, so use it with caution.

Doctors often use NSAIDs for headache pain and inflammation, but with concussions, they usually consider them only after ruling out bleeding risk.

The most common over-the-counter NSAIDs are:

And their typical adult doses are:

  • Ibuprofen: 200 to 400 mg every 4 to 6 hours as needed
  • Naproxen: 220 mg every 8 to 12 hours as needed
  • Aspirin: 325 mg every 4 to 6 hours as needed

A 2023 study review found that NSAIDs may help with post-concussion headaches, especially when they resemble migraines. But overuse can lead to rebound headaches.

Another research review also suggests avoiding aspirin and certain NSAIDs right after a concussion, since they may increase the risk of bleeding in the brain.

NSAIDs may also cause other side effects, such as:

Triptans, such as sumatriptan (Imitrex) or rizatriptan (Maxalt), are medications that act on serotonin receptors in the brain to relieve migraine symptoms.

A 2025 study found that people with post-traumatic migraines responded to triptans much like those with primary migraine. Experts recommend reserving them for severe headaches when NSAIDs don’t help.

Dosing can vary depending on the specific triptan. Always follow your doctor’s instructions to ensure safety.

Common side effects include:

Amitriptyline is a tricyclic antidepressant that doctors sometimes use off-label for pain, sleep disturbances, and migraine prevention.

Research shows it may improve sleep during recovery and reduce persistent post-traumatic headaches, especially when they resemble migraine or tension-type headaches.

The recommended dose is 10 to 25 mg at bedtime, increased gradually as needed.

Commonly reported side effects include:

Topiramate (Topamax) is an anti-seizure medication that doctors sometimes prescribe off-label for post-concussion headaches, especially when other treatments don’t work.

A 2020 study review found that topiramate reduced headache frequency by 57% in military patients with chronic migraine and by 31% in those with medication overuse headaches.

The recommended dose for most people is 25 to 50 mg, but some may need higher doses up to 200 mg under close medical supervision.

Possible side effects include:

Methylphenidate may help treat post-TBI depression and improve cognitive symptoms.

It’s typically used to treat ADHD or narcolepsy. With ADHD, it helps increase attention and reduce impulsiveness and hyperactivity. It’s a CNS stimulant that increases norepinephrine and dopamine in your brain.

A 2019 study suggests methylphenidate improves mental fatigue, depression, and anxiety in people following a mild TBI. Though the study notes that not everyone will be suited to this treatment, careful monitoring is needed by a healthcare professional.

Though the findings are positive, more clinical trials need to be done to confirm the effects.

Melatonin is a natural hormone that regulates the sleep-wake cycle. It’s also available as an over-the-counter sleep aid in the United States.

Since sleep problems are common after a concussion, doctors may recommend melatonin before prescription sleep aids due to its safety and ability to regulate the sleep-wake cycle.

A 2023 study review found that melatonin can improve sleep quality in people recovering from traumatic brain injury. It may also help protect brain cells and support recovery after a concussion.

There’s no standard dose for melatonin since the FDA doesn’t regulate it as a medication. However, studies have tested 0.1 mg to 10 mg, usually taken within two hours of bedtime.

Melatonin may cause various side effects, including:

The Food and Drug Administration (FDA) approves sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI) antidepressant, to treat depression and anxiety.

A 2022 study review found that people with persistent post-concussion symptoms are at a higher risk of developing symptoms of depression.

Research from 2021 shows that sertraline can improve depression after a concussion, though the benefit is small and may vary by the severity of the injury.

It also suggested sertraline may ease anxiety, though evidence remains limited. Doctors often prefer it for mood symptoms because it’s safer than older groups of antidepressants.

The starting dose of sertraline is 25 to 50 milligrams (mg) once daily, with gradual increases if needed.

Side effects include:

Nausea and vomiting commonly occur in the first days after a concussion, the Centers for Disease Control and Prevention (CDC) reports.

Doctors often prescribe ondansetron (Zofran) to treat these symptoms. It works by blocking serotonin receptors in the gut and brain that trigger the urge to vomit.

Research from 2023 shows that ondansetron provides short-term relief of nausea and vomiting after a concussion, especially in children and teenagers.

The adult dose of ondansetron for nausea and vomiting is 4 to 8 mg every 8 hours as needed. Dosing for children depends on weight and should be determined by a doctor.

Ondansetron for concussion-related nausea should only be given under medical supervision, especially in children and teenagers, because dosage varies.

Like other medications, ondansetron may cause side effects, such as:

  • constipation
  • dry mouth
  • headache
  • fatigue

The FDA hasn’t approved any medications to treat concussions. Instead, doctors may prescribe off-label options such as triptans to help ease symptoms like headaches, nausea, or sleep problems.

If you’re recovering from a concussion, talk with a healthcare professional before taking any medication. They can guide safe choices and help you create a recovery plan.