The patient with diabetes who complains of painful symptoms due to neuropathy challenges their physician to alleviate their distress and discomfort — not always an easy task. And yet, diabetes and painful diabetic neuropathy are so common that all doctors need to become aware of potentially successful treatment approaches.

One population-based study of people with type 2 diabetes (about 90% of all diabetes patients) found that 26.4% suffered painful diabetic neuropathy.¹ So the condition is present, but often, the diagnosis isn’t made in the physician’s office, because the patient fails to complain of the pain, not understanding that it’s a complication of diabetes.

After the diagnosis of painful diabetic neuropathy (PDN) is made, an essential principle to understand is that improving glycemic control, even to perfect levels, won’t be sufficient to relieve the painful symptoms of neuropathy. Optimal diabetes control that aims for an A1c level less than 7%, with attention given to modifiable risk factors such as hypertension and hyperlipidemia, is essential to prevent progression of neuropathy, but there’s no good evidence that such intervention relieves existing pain. It’s reasonable to warn the patient of this, to avoid disappointment.

A second important principle is to have a consistent way to measure the pain level, such as a visual analogue scale (VAS) that can be followed easily. Third, remember to consider co-morbidities, such as concomitant depression, that may require different attention. Finally, keep in mind that PDN is a chronic, debilitating condition that can persist for years, and requires appropriate long-term care from the physician.

Adjuvant analgesics

Since patients continue to experience painful symptoms despite improved glycemic control, other methods are needed to control pain that’s distressing, typically with a VAS ≥ 4/10. According to the 2009 Canadian Diabetes Association guidelines, evidence supports the use of antidepressant and anticonvulsant agents as adjuvant analgesics (Table 1).²

The most commonly used drugs are tricyclic antidepressants (amitriptyline, desipramine, nortriptyline) and the anticonvulsant gabapentin. More recently, newer agents have been approved by Health Canada for treating painful symptoms in PDN, including the anticonvulsant pregabalin and the SNRI antidepressant duloxetine. Opioid analgesics such as tramadol or oxycodone have a role, but are generally held in reserve for when anticonvulsants and antidepressants fail to control pain. Other drugs used in PDN are the anticonvulsants and mood stabilizers carbamazepine, lamotrigine, oxcarbazepine, and mexiletine, whose primary use is as an anti-arrhythmic. Drug combinations may be useful, but take care in prescribing multiple medications due to the potential for adverse events in a patient population already taking several medications for diabetes and co-morbidities. In selected individuals, topical agents such as lidocaine or isosorbide dinitrate may provide relief without undue systemic side effects.

For adjuvant analgesics, the rule is to start with a low dose and gradually titrate upwards to tolerability, or to an analgesic dose. It’s important to recall that very few people have total relief, but many will have a reduction in their pain level to a tolerable state, such as VAS 6/10 reduced to 2-3/10.

Variable response times

Response times vary. For gabapentin, pregabalin and duloxetine, the effect is observed after 2 weeks of treatment and doses can be adjusted then. For tricyclic antidepressants, a gradual titration of dose is required to avoid excessive drowsiness and unsteadiness, and increments are made weekly to biweekly, so that the treatment schedule can extend over weeks to several months. With opioids, a faster response is observed. Naturally, if the patient has significant depression associated with PDN, then antidepressant therapy is preferable to anticonvulsant treatment.

If individual agents fail, drug combinations can be tried (such as gabapentin plus amitriptyline). The physician needs to recall that 40-50% of patients either won’t tolerate these treatments or won’t respond. Some sufferers report benefit from non-traditional interventions such as vitamin therapy or acupuncture, but the evidence for such treatment is insubstantial. Refractory patients can be referred to specialized pain physicians/clinics for further treatment.

 

References

1. Davies M, Brophy S, Williams R, Taylor A. Diabetes Care 2006;29:1518-22.
2. Bril V, Perkins B, Committee CDACPGE. 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada; Neuropathy. Can J Diabetes 2008;32:S140-2