Common Neuropathy Medications & What to Watch For

How neuropathy pain is treated

Neuropathy pain often stems from overactive or damaged nerves sending extra signals. Medicines can quiet those signals, reduce pain, and help you function better. Most people need a combination of approaches, such as good condition control, movement, sleep support, and a trial of one medicine at a time to see what helps.

There is no single best drug for everyone. You and your clinician can choose a starting option based on your health conditions, other medicines, and possible side effects. If the first option does not help after a fair trial or causes side effects, it is reasonable to switch to a different class.

Common medication options

Acetaminophen and non-steroidal anti inflammatory drugs

Acetaminophen and non-steroidal anti inflammatory drugs may ease mild pain but usually do not relieve nerve pain on their own.
What to watch for

• Acetaminophen is found in many cold and pain products. Taking too much can harm your liver. Read every label and add up all sources.
• Non-steroidal anti inflammatory drugs can irritate the stomach, raise blood pressure, affect the kidneys, and increase bleeding risk.
• Consult your clinician or another healthcare professional before using these medicines regularly, especially if you have heart, kidney, stomach, or bleeding conditions.

Antidepressants used for nerve pain

Some antidepressants help nerve pain at lower doses than are used for depression.

Serotonin norepinephrine reuptake inhibitors

• Duloxetine is commonly used for painful diabetic peripheral neuropathy and other neuropathic pain.

What to watch for

• Nausea, dry mouth, sleep changes, dizziness, or sweating are common early on and often improve.
• Duloxetine can raise blood pressure in some people, so monitoring is helpful.
• Risk of serotonin syndrome increases if combined with other medicines that raise serotonin. Seek urgent care for agitation, fever, stiff muscles, or confusion.

Tricyclic antidepressants

• Amitriptyline and nortriptyline can reduce nerve pain, often taken in the evening due to drowsiness.
  What to watch for
• Dry mouth, constipation, blurry vision, dizziness, and daytime sleepiness are common.
• These medicines may worsen certain heart rhythm problems and are not ideal for people with significant heart disease, glaucoma, or trouble with urination.
• Start low and go slow with your clinician guiding dose changes.

Anticonvulsants for nerve pain

Gabapentin and pregabalin calm overactive nerve signaling and are widely used for neuropathic pain.
What to watch for

• Drowsiness, dizziness, swelling in legs or feet, and weight gain can occur.
• If you have kidney concerns, the dose needs adjustment.
• Combining these drugs with opioids, benzodiazepines, or alcohol can slow breathing and cause severe sedation. Avoid risky combinations.
• Do not stop suddenly without a taper plan from your clinician.

Topical options

Topical treatments can target pain in defined areas with fewer whole body side effects.

Lidocaine

• Available as cream, gel, or patches for localized nerve pain such as post shingles pain.

What to watch for

• Skin irritation or numbness where applied.
• Follow label limits on the number of patches and time they can be worn. Avoid heat over a patch.

Capsaicin

• Lower strength creams are available without a prescription. High strength eight percent patches are applied in a clinic and can reduce certain types of nerve pain, including diabetic foot pain.

What to watch for

• Burning or redness at the site is common at first.
• The clinic patch may briefly raise blood pressure during or after application. Your care team will monitor you during treatment.

Opioids and tramadol

Opioids and tramadol are generally not recommended for long term management of neuropathic pain.
What to watch for

• Risks include tolerance, dependence, constipation, falls, hormonal effects, and overdose.
• Tramadol can trigger seizures and serotonin syndrome, especially with other medicines that raise serotonin.
• If used, they should be short term and closely monitored when other options are not effective or suitable.

Vitamins and supplements

Vitamin B12

• A lack of vitamin B12 can cause or worsen neuropathy. Replacement can help when there is a clear deficiency.
  What to watch for
• Older adults, people with certain stomach or intestinal conditions, and those taking metformin for diabetes are at higher risk of low B12. Blood testing can confirm deficiency.
• Taking high dose supplements without a confirmed need is usually not helpful. Discuss testing and the right form and dose with your clinician.

Other supplements

• Some people try alpha lipoic acid or other products. Evidence is mixed and quality varies. Talk with your clinician before starting any supplement, especially if you take other medicines or have chronic conditions.

What to watch for and when to seek care

Call your clinician promptly if you notice

• New weakness, trouble walking, or falls
• Numbness spreading quickly or severe loss of feeling
• Severe rash, swelling of lips or tongue, or trouble breathing
• Signs of liver trouble such as yellowing of skin or eyes, dark urine, or right upper belly pain
• Worsening mood changes or thoughts of self harm
• Symptoms of serotonin syndrome such as agitation, fever, sweating, shaking, stiff muscles, rapid heart rate, or confusion
• Extreme sleepiness, slow or shallow breathing, or blue tinted lips or fingers, especially if taking gabapentin or pregabalin with other sedatives

‍
An Understood Care advocate can help you decide next steps, contact your clinician, and document symptoms so your treatment is adjusted quickly. Ready for support? Call (646) 904-4027 or sign up at https://app.understoodcare.com.

Safe use tips

Take the right dose at the right time

• Start low and increase gradually with your clinician’s guidance.
• Give each medicine a fair trial at a tolerable dose before deciding it does not help.
• Keep a simple daily log of doses, pain levels, and side effects to share at visits.

Avoid risky combinations

• Do not mix gabapentin or pregabalin with alcohol, opioids, or other sedatives.
• Be careful with combinations that raise serotonin such as certain antidepressants, tramadol, migraine triptans, and some cough medicines.
• Read every label to avoid taking acetaminophen from multiple products at once.

Protect your liver, kidneys, and heart

• Stay within safe daily limits for acetaminophen and avoid it if your clinician advises against it.
• Use nonsteroidal anti inflammatory drugs cautiously if you have kidney disease, heart disease, high blood pressure, or a history of stomach bleeding.
• If you have kidney disease, ask about dose adjustments for gabapentin or pregabalin.
• If you have heart rhythm problems or glaucoma, discuss tricyclic antidepressants with your clinician before use.

Adjust for your health conditions

• Diabetes control can reduce nerve pain over time.
• Sleep, movement, and foot care matter.
• If you are over age 65, ask your clinician to review doses and side effects more often.

Questions to ask your clinician

• Which class is the best starting choice for me and why
• What side effects should I expect in the first two weeks
• How and when will we increase the dose or switch to a different option
• What interactions should I avoid with my other medicines or supplements
• How long should I try this before we reassess
• What non medicine steps can I add to help with pain and function

How Understood Care can help

If you are managing neuropathy and medication side effects, you do not have to do it alone. Understood Care can help you prepare questions for your visit, track side effects, check interactions, and coordinate with your clinician. See the related Understood Care guides listed in the References.

FAQ

• What is neuropathy pain and how is it treated?
  Neuropathy pain often comes from damaged or overactive nerves sending extra signals. Treatment usually combines good control of the underlying condition, movement and sleep support, and medicines that calm nerve signals. There is no single best drug for everyone. Your clinician will help you try one medicine at a time at careful doses and switch to another type if it does not help or causes side effects.
• Do over the counter pain relievers help neuropathy?
  Acetaminophen and non steroidal anti inflammatory drugs may ease mild aches but usually do not control nerve pain on their own. Acetaminophen can harm the liver if you take too much or use multiple products that contain it. Non steroidal anti inflammatory drugs can irritate the stomach, raise blood pressure, affect the kidneys, and increase bleeding risk. Ask your clinician before using them regularly, especially if you have heart, kidney, stomach, or bleeding problems.
• Which antidepressants are used for nerve pain?
  Some antidepressants help nerve pain at lower doses than are used for depression. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is commonly used for painful diabetic neuropathy and other nerve pain. Tricyclic antidepressants such as amitriptyline or nortriptyline can also help and are often taken in the evening.
• What should I watch for with duloxetine and other SNRIs?
  Duloxetine may cause nausea, dry mouth, dizziness, sweating, or sleep changes, especially in the first weeks. It can raise blood pressure in some people, so monitoring is useful. Combining duloxetine with other medicines that increase serotonin raises the risk of serotonin syndrome. Seek urgent care for agitation, fever, stiff muscles, or confusion.
• What should I watch for with tricyclic antidepressants like amitriptyline?
  Amitriptyline and nortriptyline often cause dry mouth, constipation, blurry vision, dizziness, and daytime sleepiness. They can worsen some heart rhythm problems and may not be a good choice for people with significant heart disease, glaucoma, or trouble with urination. Doses should start low and increase slowly under your clinician’s guidance.
• How do gabapentin and pregabalin help neuropathy pain?
  Gabapentin and pregabalin calm overactive nerve signaling and are widely used for neuropathic pain. Many people take them in divided doses during the day and at night. Drowsiness, dizziness, swelling in the legs or feet, and weight gain are common side effects. People with kidney problems usually need lower doses.
• Are there safety concerns with gabapentin and pregabalin?
  Yes. These medicines can increase sedation and slow breathing when used with opioids, benzodiazepines, sleep medicines, or alcohol. Avoid combining them with other sedating drugs unless your clinician is closely supervising. Do not stop them suddenly without a taper plan from your clinician.
• What topical treatments can help localized nerve pain?
  Lidocaine creams, gels, and patches can numb overactive skin nerves in a painful area, such as post shingles pain. They can cause local irritation or numbness where applied. Follow label limits for how many patches you can use and how long you can wear them, and do not use heat over a patch. Capsaicin creams and in clinic eight percent patches can reduce certain types of nerve pain, including diabetic foot pain. Burning or redness at the site is common at first, and clinic patches may briefly raise blood pressure, so your team will monitor you.
• Are opioids or tramadol good options for neuropathy pain?
  Opioids and tramadol are generally not recommended for long term neuropathy pain. They carry risks of tolerance, dependence, constipation, falls, hormonal changes, and overdose. Tramadol also increases seizure risk and can contribute to serotonin syndrome, especially with certain antidepressants or other drugs. If used at all, they are usually short term and closely monitored when other options are not effective or suitable.
• Can vitamins or supplements help neuropathy?
  Vitamin B12 replacement can help if you have a confirmed B12 deficiency, which itself can cause or worsen neuropathy. Older adults, people with certain stomach or intestinal conditions, and those taking metformin are at higher risk for low B12 and may need blood tests. Taking high dose vitamins without a clear need is rarely helpful. Some people try alpha lipoic acid or other supplements, but evidence is mixed and quality varies. Always talk with your clinician before starting supplements.
• What side effects or warning signs should make me call my clinician right away?
  Call your clinician promptly if you notice new weakness or trouble walking, frequent falls, quickly spreading numbness, severe rash, yellowing of the skin or eyes, dark urine, new mood changes, or thoughts of self harm. Seek urgent care for swelling of the lips or tongue, trouble breathing, severe or spreading rash with dizziness, signs of serotonin syndrome such as agitation, fever, shaking, stiff muscles, fast heart rate, or confusion, and for extreme sleepiness or very slow breathing, especially if you take gabapentin or pregabalin with other sedating medicines.
• How can I use neuropathy medicines as safely as possible?
  Take the right dose at the prescribed times and increase slowly only with your clinician’s guidance. Give each medicine a fair trial at a tolerable dose before deciding it does not help. Keep a simple log of doses, pain levels, and side effects. Avoid risky combinations such as gabapentin or pregabalin with alcohol or other sedatives, and do not take acetaminophen from multiple products at once. If you have kidney, liver, heart, or eye conditions, ask your clinician how these affect medicine choices and dosing.
• What questions should I ask my clinician about neuropathy medicines?
  Ask which medicine class is the best starting choice for you and why, what side effects you might see in the first two weeks, how and when doses will be increased or changed, what interactions to avoid with your other medicines or supplements, how long to try each medicine before reassessment, and what non medicine steps you can add for pain and function such as physical therapy, footwear changes, or sleep strategies.
• How can Understood Care help me manage neuropathy medications and side effects?
  Understood Care advocates can help you build a clear medication list, track side effects, prepare focused questions for visits, and coordinate with your clinicians when changes are needed. They can also help check for interactions, organize refills, and support non medicine strategies that fit your daily life. For one to one support, you can call (646) 904 4027 or sign up at https://app.understoodcare.com.

References

• Mayo Clinic. Peripheral neuropathy diagnosis and treatment. https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/diagnosis-treatment/drc-20352067
• Mayo Clinic. Diabetic neuropathy diagnosis and treatment. https://www.mayoclinic.org/diseases-conditions/diabetic-neuropathy/diagnosis-treatment/drc-20371587
• American Academy of Neurology. Oral and topical treatment of painful diabetic polyneuropathy practice guideline update summary Neurology 2022. PubMed record. https://pubmed.ncbi.nlm.nih.gov/34965987
• Neurology journal. Oral and topical treatment of painful diabetic neuropathy practice guideline update. https://www.neurology.org/doi/10.1212/WNL.0000000000013038
• FDA Consumer Update. Do not overuse acetaminophen. https://www.fda.gov/consumers/consumer-updates/dont-overuse-acetaminophen
• FDA Drug Safety Communication. Serious breathing problems with gabapentin and pregabalin. https://www.fda.gov/safety/medical-product-safety-information/neurontin-gralise-horizant-gabapentin-and-lyrica-lyrica-cr-pregabalin-drug-safety-communication
• MedlinePlus. Gabapentin drug information. https://medlineplus.gov/druginfo/meds/a694007.html
• MedlinePlus. Pregabalin drug information. https://medlineplus.gov/druginfo/meds/a605045.html
• Mayo Clinic. Lidocaine topical application route. https://www.mayoclinic.org/drugs-supplements/lidocaine-topical-application-route/description/drg-20072776
• MedlinePlus. Lidocaine transdermal patch. https://medlineplus.gov/druginfo/meds/a603026.html MedlinePlus
• Mayo Clinic. Capsaicin topical route. https://www.mayoclinic.org/drugs-supplements/capsaicin-topical-route/description/drg-20062561
• MedlinePlus. Duloxetine drug information. https://medlineplus.gov/druginfo/meds/a604030.html
• Mayo Clinic. Amitriptyline oral route. https://www.mayoclinic.org/drugs-supplements/amitriptyline-oral-route/description/drg-20072061
• FDA prescribing information for tramadol oral tablets. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020281s040lbl.pdf
• NIH Office of Dietary Supplements. Vitamin B12 Health Professional Fact Sheet. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional Office of Dietary Supplements
• MedlinePlus Medical Encyclopedia. Vitamin B12 deficiency anemia. https://medlineplus.gov/ency/article/000574.htm MedlinePlus
• Cleveland Clinic. Neuropathic pain overview and treatments. https://my.clevelandclinic.org/health/diseases/15833-neuropathic-pain Cleveland Clinic

This content is for education only and does not replace professional medical advice. If you have new weakness, severe pain, fever with confusion, chest pain, or trouble breathing, call emergency services.