Understanding New Guidelines to Improve Management of Painful Diabetic Neuropathies

Brian Callaghan, MD, MS

Despite the fact that slightly more than one-third of patients with diabetic peripheral neuropathy experience pain, limited disease-modifying treatments exist. For patients who have confirmed diabetic neuropathic pain, clinicians have typically recommended firstline treatments such as tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and voltage-gated calcium ligands. If all 3 classes and combination therapy fail, the next step has been to prescribe opioids or tramadol, an opioid analgesic.

As time has gone along, those within the medical field, including organizations such as the American Academy of Neurology, have strayed away from opioids to treat chronic pain, citing their harmful effects and increased overdose rates. At the 2022 American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) annual meeting, Brian Callaghan, MD, MS, gave a talk about the need to change strategies for diabetic and inflammatory neuropathies, including Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuopathy (CIDP). Callaghan drew attention to several previous studies that highlighted the downsides to opioids, including their associations with functional status, adverse outcomes, and mortality.

The new guidelines state that first line treatments should be TCAs, SNRIs, gabapentinoids, and sodium channel blockers, followed by other topicals including capsaicin and lidocaine, and nonpharmacological options including cognitive behavioral therapy, mindfulness, and exercise. Additionally, they recommend avoiding opioids including tramadol and tapentadol. Callaghan, an associate professor at the University of Michigan, noted that the current practice is far from ideal. At AANEM 2022, he sat down with NeurologyLive® to share his thoughts on the need for change and the importance of correctly treating these conditions.

NeurologyLive^®: Why did you choose to focus in on this topic specifically?

Brian Callaghan, MD: These neuropathies are either super common, like diabetic neuropathy, or in the case of GBS and CIDP, highly treatable, and can cause lots of major problems to patients. Both of those are reasons why it's so important. There haven't been guidelines for several years for most of these, and then for GBS, there hasn't been a guideline for a long time, many decades.

Have there been gaps in how we treat diabetic and inflammatory neuropathies?

For diabetes, probably the biggest gap is that there's high opioid use for the pain. As evolving data has come out, that is probably not the best approach. There are even certain medicines that are opioids that a lot of physicians don't think of them as opioids, so that's something that we call attention to. That's probably the biggest thing for the painful diabetes piece. For GBS, those guidelines aren't quite out yet, so we'll see what they what they show. For CIDP, probably the biggest gap is in diagnosis. We know that we over diagnose patients with CIDP, and so we get it wrong a decent amount of time. These guidelines I think, are meant to clarify how to appropriately diagnose people with CIDP. From a treatment perspective, I think people do pretty well.

Is there a reason why there are complications or complexities with the diagnosis?

The diagnosis is tricky. You have to first be very good at EMG and nerve conduction studies. And sometimes patients don't quite make criteria, which gets people confused, and people don't want to miss a treatable problem. It's not always a real black and white diagnosis. How do you deal with those gray areas? And what should make you think someone has CIDP or not? When to do therapy is actually tricky as well.

Is this a treatment area that may fly under the radar?

With something like diabetic neuropathy, oftentimes, people don't talk about it enough because it doesn't usually lead to death or something super morbid; although, it can lead to amputations and things less common. But what's so important about is it's the most common neuropathy by far and away. We have to pay attention to things that are super common, even if they're not the worst diseases to have. In contrast, GBS and CIDP are nowhere near as is common, but they do lead to such bad problems. We have to be able to identify them, treat them with the appropriate things, avoid over diagnosis, and get the right treatments to the right people. It’s kind of the Yin and Yang in some ways.

How do CIDP and GBS differ from each other in terms of diagnosis and treatment?

One presents usually very quickly, and one very slowly. GBS happens quickly and CIDP happens much more slowly, but there's that gray area where it's not as clear and those are the tricky patients. But usually either time tells the tale and our response to treatments. The treatments are quite similar. We'd like to use IVIG and plasmapheresis for both. Steroids, however, only help people with CIDP and not people with GBS. There are differences with GBS, you really only treat it once. It seems like if you give IVIG once, maybe twice would be better. But we now have good data that treating a second time actually causes harm without helping people. GBS is a one-time thing, whereas CIDP, we have to treat year after year.

What types of long-term impacts/goals do you have for these guidelines?

It's different for each guideline. For the painful diabetic neuropathy, we do have several medicines that work, but none of them work great. It highlights the need for a new treatment. Pain is a really complex thing, but our current therapies are just okay. We just need a novel way of treating pain that we don't currently have for GBS and CIDP. We've had a lot of the same therapies for decades. Again, while we do have good treatments, it highlights “what's that next step?” It'll probably be kind of a novel thing that we don't have available now. That's where the future of these diseases is. With CIDP, the other piece is making sure that we have a good way of diagnosing people and putting people in the right category, because otherwise you end up with a lot of over treatment or under treatment, which can cause a lot of problems.

Transcript edited for clarity. Click here for more coverage of AANEM 2022.