Navigating Neuropathy: How to Treat Neuropathic Pain in People with Serious Illness

Neuropathic pain is extremely common among patients with serious illness. It takes a significant toll on many patients’ quality of life, and research suggests it’s a problem that is only becoming more prevalent.

Neuropathic pain is easy for just about anyone to recognize—neuropathy isn’t a diagnosis that likes to hide. Patients typically report pain, numbness, and weakness, using descriptions like tingling, burning, or “pins and needles.” It often disrupts sleep, can prevent someone from walking unassisted, and creates barriers to performing daily tasks such as opening jars, holding a cup of coffee, or buttoning shirts.

While diagnosing neuropathy is straightforward, treating it is more challenging. Most treatments are only moderately effective at best or have intolerable side effects that are intolerable. Since it takes time and patience to treat neuropathy, you might end up discussing other therapeutic treatments with your patients while you wait.

Given its prevalence in patients with serious illness, this blog explores neuropathic pain treatment to help you effectively support and manage your patients’ symptoms.

For neuropathic pain, it's important to remember the common causes—chemotherapy, diabetes, hypothyroidism, alcohol use, vitamin B12 deficiency, post-herpetic neuralgia, or procedures like mastectomies and thoracotomies. For treatment, the three main classes of drugs include:

• Serotonin-norepinephrine reuptake inhibitors (SNRIs): Duloxetine and venlafaxine
• Calcium channel alpha-2-delta ligands: Gabapentin and pregabalin
• Tri-cyclic antidepressants (TCAs): Most commonly used TCAs include amitriptyline and nortriptyline

Deciding which treatment to start with can be a challenge. It’s helpful to first consider the precipitating cause of a patient’s neuropathy. If needed, you can run tests to check thyroid disorders or vitamin B-12 deficiencies or check their hemoglobin A1C if they’re at risk for diabetes to ensure reversible etiologies are addressed. In addition, it is important to take a step back and consider their other co-morbid medical conditions and symptoms, as this can influence which neuropathic modality is best suited for your patient.

Duloxetine might be a good choice for a cancer patient with chemotherapy-induced peripheral neuropathy (CIPN) as it has demonstrated efficacy in a randomized controlled trial for CIPN and is considered first-line for this condition. I have recommended TCA’s and SNRI’s for patients with serious illness who are experiencing neuropathy and depression.

As an example, a patient with metastatic ovarian cancer and a history of cardiac arrhythmias and depression had developed tingling and burning in her hands, lower legs, and feet due to undergoing treatment with carboplatin and paclitaxel. Because she was also experiencing symptoms of deepening depression, it made sense to start her on duloxetine. Meanwhile, a patient who is already taking an antidepressant such as sertraline (that would interact with an SNRI or TCA) and doesn’t want to stop taking it could be a candidate for gabapentin or pregabalin. For those with neuropathy and insomnia, I may recommend a TCA like nortriptyline, which can help with both, particularly if they are not at risk for the cardiac and anticholinergic side effect profile of TCA’s; secondary amine TCA’s (nortriptyline and desipramine) are better tolerated with fewer anticholinergic side effects.

As you consult with patients who have neuropathic pain, it may help to remind yourself and your patients that this likely won’t be a quick-and-easy solution. Here are my strategies for navigating this process while helping your patients prepare for the path ahead.

When it comes to neuropathic pain management, we want to give our patients hope, but we also need to set realistic expectations. They may be frustrated that their pain isn’t going away as quickly as they’d hoped. We must explain that once nerves become damaged, they take a long time to heal.

We also need to ensure that patients understand that medications can take time to titrate to an effective level and that it is important not to abandon a medication that might ultimately be helpful prematurely. In addition, the first treatment may not work or cause side effects that are hard to tolerate. You may need to try different doses, medicines, or even a series of treatments to find one that works well—so it may take a while. Setting reasonable expectations from the start helps patients so they do not get discouraged and give up.

For neuropathy, we typically approach treatment by starting one medication and then titrating up as high as we can until the medication controls the symptoms or the patient experiences side effects. If the pain persists, we then sequentially add a second medication. For example, I might combine an SNRI with gabapentin or pregabalin. However, it would not be appropriate to combine a tricyclic with an SNRI since that would essentially be doubling up on antidepressants, raising the risk of serotonin syndrome. Although it has been proposed that starting with low doses of two separate classes might lead to better pain control with fewer side effects this approach requires further study.

Many seriously ill patients with neuropathy do benefit from opioid therapy, and while opioids have been shown to effectively improve neuropathic pain, it’s important to consider the risk-benefit ratio for each individual patient. The longer the patient’s prognosis, the higher the risk associated with using opioids. Opioids might make sense for a patient with advanced cancer and a limited prognosis. However, for a relatively young patient with diabetes who might live for many years, the risks of long-term opioid therapy likely outweigh the benefits.

It’s important to assess each patient’s gait stability and fall risk, and the need for assistive devices. Discussing good foot care/monitoring for wounds, safe footwear choices, and driving safety is critical, which loss of proprioception from the neuropathy, as well as sedation/decreased reaction time from medications, can affect. Physical therapy and occupational therapy can help.

The bottom line is that neuropathy is complex, and requires trust and communication between clinicians and patients. Hopefully, in the future, we’ll have treatments that are more effective at reducing or even eliminating the pain and discomfort that develops as a result of nerve damage. Perhaps research into predictive markers will yield some promising new treatments.

In the meantime, we must always be honest with our patients. I’ve found that patients respond best when they know what to expect from the beginning. Our job is to show them empathy and assure them that together, we will find the best available treatment options.

Edited by Melissa Baron. Clinical review by Andrew Esch, MD, MBA.