What medication is used for fibromyalgia nerve pain?

October 6, 2025 •

4 min read

Chronic nerve pain in fibromyalgia is believed to stem from a phenomenon called central sensitization, where the central nervous system over-amplifies pain signals. To address this, several medications are used for fibromyalgia nerve pain, including a few that are specifically FDA-approved for the condition. Managing this complex condition often requires a personalized approach, combining pharmacological and non-pharmacological therapies.

Quick Summary

This article explores the pharmacological treatments for fibromyalgia nerve pain, focusing on FDA-approved drugs like pregabalin, duloxetine, and milnacipran. It also details commonly used off-label options, such as gabapentin and tricyclic antidepressants, and reviews the effectiveness and common side effects of these medications.

Key Points

FDA-Approved Medications: Pregabalin (Lyrica), duloxetine (Cymbalta), milnacipran (Savella), and sublingual cyclobenzaprine (Tonmya) are the four FDA-approved drugs for fibromyalgia.
Mechanism of Action: These medications work by calming overactive pain-sensing nerves in the central nervous system, rather than acting as traditional anti-inflammatories.
Off-Label Options: Other medications like gabapentin (Neurontin), amitriptyline, and low-dose naltrexone (LDN) are commonly used off-label to manage specific symptoms.
Individualized Treatment: The effectiveness of medications varies significantly among individuals, and finding the right drug or combination often requires a personalized approach.
Multimodal Approach: Pharmacological treatment is most effective when combined with non-drug therapies such as exercise, physical therapy, and cognitive behavioral therapy (CBT).
Management of Side Effects: Side effects like dizziness, weight gain, and nausea are common, and patients often need to adjust treatment or switch medications to find a tolerable option.
Limited Opioid Use: Strong opioids are generally not recommended for fibromyalgia due to limited evidence of long-term benefit and risk of dependence, though tramadol is occasionally used for short-term flares.

Understanding Fibromyalgia and Central Sensitization

Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and other symptoms like sleep disturbances and cognitive issues. The pain experienced by people with fibromyalgia is not simply muscular; it is largely driven by central sensitization, a process in which the central nervous system becomes overactive and amplifies pain signals. This means that ordinary sensations can be perceived as painful, leading to a lower pain threshold and heightened sensitivity to pain (hyperalgesia). Pharmacological treatment for fibromyalgia nerve pain aims to calm this overactive nervous system rather than target local inflammation, which is why traditional pain relievers like NSAIDs are often ineffective.

FDA-Approved Medications for Fibromyalgia Nerve Pain

There are three medications specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of fibromyalgia. These drugs work by targeting the central nervous system's pain pathways to reduce nerve sensitivity.

Pregabalin (Lyrica): An anticonvulsant medication that binds to a specific protein on nerve cells to reduce the release of neurotransmitters involved in pain signaling. It is used to lessen nerve pain and can also help improve sleep. It has shown modest effectiveness for some patients, with about 1 in 10 experiencing substantial pain relief in clinical trials.
Duloxetine (Cymbalta): A serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant that increases the levels of serotonin and norepinephrine in the brain and spinal cord. These neurotransmitters are involved in modulating pain signals, and increasing their levels can help reduce pain and improve mood.
Milnacipran (Savella): Another SNRI that works similarly to duloxetine but has a more pronounced effect on norepinephrine. It helps reduce pain and fatigue associated with fibromyalgia. For some patients, milnacipran has shown improvement in pain and overall well-being.
Tonmya (sublingual cyclobenzaprine): Approved by the FDA in August 2025, this is a new formulation of a muscle relaxant intended to improve sleep and reduce pain. It is taken at bedtime and is designed for rapid absorption with fewer next-day sedative effects.

Comparing FDA-Approved Fibromyalgia Medications


Feature	Pregabalin (Lyrica)	Duloxetine (Cymbalta)	Milnacipran (Savella)
Drug Class	Anticonvulsant	SNRI Antidepressant	SNRI Antidepressant
Mechanism	Binds to voltage-gated calcium channels to modulate neurotransmitter release and calm overactive nerves.	Increases serotonin and norepinephrine levels in the central nervous system to modulate pain signals.	Increases serotonin and norepinephrine levels, with a stronger effect on norepinephrine, to regulate pain pathways.
Administration	Taken as directed by a healthcare professional.	Taken as directed by a healthcare professional.	Taken as directed by a healthcare professional.
Common Side Effects	Dizziness, drowsiness, weight gain, blurred vision, swelling.	Nausea, dry mouth, constipation, increased sweating, fatigue.	Nausea, headache, hot flushes, increased heart rate, constipation.

Off-Label and Alternative Pharmacological Treatments

In addition to FDA-approved drugs, healthcare providers may prescribe other medications off-label to manage fibromyalgia symptoms, tailoring the treatment to the patient's specific needs.

Gabapentin (Neurontin): Like pregabalin, this is an anticonvulsant that can help reduce nerve pain by affecting calcium channels in the nervous system. It is often used to improve sleep quality and pain.
Tricyclic Antidepressants (TCAs): Older antidepressants like amitriptyline (Elavil) are often prescribed at low doses, particularly for their sedative properties, which can improve sleep and reduce pain. Side effects like drowsiness and dry mouth are common.
Muscle Relaxants: Drugs like cyclobenzaprine (Flexeril) are used to relieve muscle tension and promote sleep. A newer, sublingual formulation (Tonmya) was recently approved specifically for fibromyalgia.
Tramadol: A weak opioid and SNRI, tramadol is sometimes used for severe short-term pain flares, though long-term opioid use is not recommended due to limited evidence of effectiveness and risk of dependence.
Low-Dose Naltrexone (LDN): This opioid receptor antagonist is thought to work by modulating immune cells in the central nervous system to reduce pain. Some studies suggest it benefits a portion of fibromyalgia patients with generally mild side effects.
Medical Cannabis/Cannabinoids: Some evidence suggests cannabinoids may help with pain and sleep in fibromyalgia patients. While regulated and approved in some regions, conflicting results and the need for more research mean its use remains controversial and state-dependent.

Combining Medications for Optimal Results

Treating fibromyalgia is not a one-size-fits-all process. Many patients find that a combination of medications works best, especially when addressing a range of symptoms beyond just nerve pain. A provider may combine an SNRI like Cymbalta to address mood and pain with a muscle relaxant like Tonmya to improve sleep quality. Some may also integrate off-label options like gabapentin if side effects or a lack of response prevent the use of FDA-approved drugs. Careful monitoring and adjustment of treatment are crucial to maximize benefits while minimizing side effects. A tailored approach is key to managing this complex and multifaceted condition.

Conclusion

Managing the nerve pain associated with fibromyalgia is a complex challenge, with medication playing a key role in a comprehensive treatment plan. The FDA has approved pregabalin, duloxetine, milnacipran, and sublingual cyclobenzaprine (Tonmya) for this purpose, but off-label medications like gabapentin, amitriptyline, and LDN are also common options. Since effectiveness varies widely and many patients experience modest relief, an individualized, multi-modal approach combining medication with non-pharmacological strategies like exercise and cognitive behavioral therapy is recommended for the best results. It is essential for patients to work closely with their healthcare provider to find the right combination of treatments and manage side effects effectively.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before starting or stopping any medication.

Frequently Asked Questions

There is no single 'best' medication, as treatment is highly individualized. The most common FDA-approved options are pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella). The best choice depends on your specific symptoms, side effect tolerance, and other health conditions.

Antidepressants like duloxetine and milnacipran, known as SNRIs, increase the levels of serotonin and norepinephrine in the central nervous system. These neurotransmitters help to modulate pain signals, effectively turning down the volume on the amplified pain caused by fibromyalgia, even if a person is not depressed.

Some patients may experience improvement within a week of starting medication, but for others, it can take several weeks or even months to feel the full effects. It is important to continue taking the medication as prescribed and communicate with your doctor about your progress.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, and pain relievers like acetaminophen, are generally not effective for the widespread, nerve-related pain of fibromyalgia. They may help with occasional muscle aches but do not address the central sensitization that is the root cause of the pain.

Most guidelines do not recommend long-term use of strong opioids for fibromyalgia due to a lack of evidence for long-term effectiveness and a high risk of side effects and dependence. Tramadol, a weak opioid with SNRI properties, may be prescribed for short-term management of severe pain flares in some cases.

An FDA-approved medication has been officially sanctioned by the Food and Drug Administration specifically for treating fibromyalgia. An off-label medication is a drug approved for a different condition but is prescribed for fibromyalgia based on clinical experience and observed benefits.

LDN stands for Low-Dose Naltrexone, an opioid receptor antagonist. It is thought to work by modulating immune cells in the central nervous system, thereby helping to reduce pain and inflammation. LDN is generally used off-label for fibromyalgia and is associated with mild side effects.