5 Non-Opioid Pain Medications With FDA Approval

Managing pain without opioids is possible — and often safer for many people. If you are concerned about developing opioid use disorder (OUD), are in recovery, or simply want to avoid the risks of opioid medications, there are effective non-opioid pain medications. These medications help manage pain while lowering the risk of dependence that comes with opioids. Many also have fewer or milder side effects, such as less drowsiness, nausea, or constipation, compared to opioids.

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Non-opioid pain medications can often be used alongside medications for OUD, supporting your recovery and helping you stay comfortable. Choosing non-opioid options also lets you manage pain without the stigma, fear, or judgment that people sometimes experience with opioid use.

This article covers several non-opioid pain medications approved by the U.S. Food and Drug Administration (FDA), how they work, and what to consider when talking with your healthcare provider.

1. Acetaminophen

Acetaminophen (sold as Tylenol and other brands) is a non-opioid painkiller used for mild to moderate pain and to reduce fever. People often take acetaminophen to relieve headaches or manage arthritis pain. You can buy acetaminophen over the counter at most drug stores, and you don’t need a prescription. It’s usually taken by mouth as a pill, but it can also be given intravenously (through a vein) in a hospital setting for faster relief.

How Acetaminophen Works

Researchers aren’t entirely sure how acetaminophen works. It’s an analgesic (pain reliever), but it does not reduce inflammation like some other pain medicines. Acetaminophen is thought to lower pain signals in the brain. Some research suggests it may also activate certain systems in the brain, including the cannabinoid and glutamatergic systems, which have important roles in behavior, visual processing, and pain sensing.

Limitations and Side Effects of Acetaminophen

Taking high doses of acetaminophen can cause serious liver damage. Do not exceed 3,750 milligrams per day — and avoid combining it with alcohol. Acetaminophen can also cause rare allergic reactions, including skin rash, itching, or hives.

2. Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs, or NSAIDs, are a group of non-opioid medicines used to treat pain that’s caused by inflammation. People often use NSAIDs for back pain, minor injuries, arthritis, menstrual cramps, and to reduce fever.

Common examples include:

• Ibuprofen (Advil, Motrin)
• Naproxen (Aleve)
• Aspirin (also called acetylsalicylic acid, or ASA)

NSAIDs are available over the counter, but a healthcare provider can prescribe stronger doses if needed. Most NSAIDs are taken by mouth as a pill, but some are available as topical creams or gels you can apply to your skin to help with muscle aches or sprains.

How NSAIDs Work

NSAIDs block cyclooxygenase (COX) enzymes, which produce prostaglandins — chemicals involved in pain, inflammation, and fever. However, these enzymes also help protect the stomach lining and support healthy kidney function, which is why NSAIDs can affect those organs.

Limitations and Side Effects of NSAIDs

Taking NSAIDs for a long time or at high doses can irritate your stomach, cause ulcers, or raise your blood pressure. You should avoid taking NSAIDs if you have certain health conditions, such as liver disease, heart failure, or if you are pregnant. Children and teens under 19 should not take aspirin, as it can cause Reye’s syndrome, a rare but serious condition that can damage the brain and liver.

3. Duloxetine

Duloxetine (brand name Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) originally developed as an antidepressant, but it’s also approved to treat chronic (long-term) pain, including nerve pain and muscle pain. Duloxetine comes in a capsule and must be prescribed by a healthcare provider.

How Duloxetine Works

Duloxetine is a non-opioid medicine that increases the levels of dopamine, serotonin, and norepinephrine in your brain. These are chemicals that help boost mood and also play a role in reducing pain signals.

Limitations and Side Effects of Duloxetine

Side effects of duloxetine are typically mild, but can include nausea, drowsiness, and dizziness. Constipation or diarrhea may also occur. Duloxetine may not be a good choice if you have certain health conditions, including a history of mental health conditions, liver disease, or kidney disease. Duloxetine may also increase the risk of suicidal thoughts in some people, particularly those under 25.

Note: If you or someone you know needs help, you can contact the 988 Suicide & Crisis Lifeline by calling or texting 988 or chatting online.

Duloxetine might take two to four weeks to work before you start feeling the full benefits. You can sometimes take it with other pain medications. However, it’s important to avoid NSAIDs because combining them can increase your risk of bleeding.

4. Gabapentin

Gabapentin (Neurontin) is an oral medication most often used to prevent seizures in people living with epilepsy. It’s also approved to treat nerve pain, including pain that can happen after shingles, restlessness, and discomfort from restless legs syndrome, and diabetic neuropathy (nerve pain in the legs or feet due to diabetes). Gabapentin is available only with a prescription from a healthcare provider.

How Gabapentin Works

Gabapentin works by calming overactive nerves. It helps reduce pain signals from nerves to the brain and can prevent seizures. Because of how it works, it may take a few weeks to start feeling relief.

Limitations and Side Effects of Gabapentin

Gabapentin can cause side effects like dizziness or sleepiness. Some people may also notice coordination or vision problems. You should avoid drinking alcohol while taking gabapentin, as it can increase drowsiness or dizziness.

Before starting gabapentin, talk to your healthcare provider if you have breathing problems, kidney disease, or changes in mood or mental health.

5. Suzetrigine

Suzetrigine (Journavx) is a relatively new drug, available by prescription. It’s approved to treat moderate to severe acute pain. Suzetrigine is taken by mouth as a tablet.

How Suzetrigine Works

Suzetrigine is different from many older pain medicines because it prevents pain signaling in the brain. It blocks a particular sodium channel on pain-sensing neurons in the body, which helps to interrupt pain signals sent to the brain. By acting only on this channel, suzetrigine may reduce pain with fewer side effects than some other pain relievers.

Limitations and Side Effects of Suzetrigine

Because suzetrigine is new, its long-term risks and benefits are still being studied. So far, the most common side effects seen in early research have been skin rash, itching, and muscle spasms. Avoid eating grapefruit or drinking grapefruit juice while taking suzetrigine — grapefruit can affect how the drug is processed in your body and may increase side effects.

Tell your healthcare provider if you have kidney or liver disease before starting suzetrigine.

Research Is Expanding Non-Opioid Pain Control Options

The approval of medications like suzetrigine shows that new treatment options are emerging for pain management. Since there are several options for pain relief, opioids are a last resort for the management of chronic pain.

These advancements could mean that the future of pain care will be less dependent on opioids, which is especially important for people who live with OUD or are working toward recovery. Choosing the right pain relief option will help you maintain your OUD recovery goals and stay confident in your ability to manage pain without fear of relapse.

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Which non-opioid pain medication has helped your pain? Let others know in the comments below.