Pharmacy U

Pharmacotherapy for managing painful diabetic neuropathy


Diabetic neuropathies are a disabling condition and the most common form has been estimated to occur in at least 20% of people with type 1 diabetes after 20 years of disease duration, and 10-15% of newly diagnosed patients with type 2 diabetes, increasing to 50% after.


By Shelley Diamond, BScPhm

Illustration by Martin Bregman


There are several treatment options for those who present with symptoms.

Symptoms of painful diabetic neuropathy have been described by patients as burning, aching, shooting, and stabbing and often present in the arms, hands, legs, and feet. Diabetic neuropathy can affect the ability of patients to perform daily activities, their sleep, their work, the way they feel, and therefore reduce their enjoyment of life.

What treatments are currently available?

Current treatments do not target the underlying nerve damage nor do they reverse the nerve damage once it has occurred. Treatment is therefore aimed at pain management. It is important to set expectations that pain will not be completely eliminated, but at very best will be reduced by 30-50%.



Pregabalin, an anticonvulsant with structural similarity to gabapentin, appears to be effective in 30-50% patients with neuropathic pain. A dose response has been shown with pregabalin, with 600mg providing more efficacy than 300mg. The lower dose may be preferred initially in older patients because of an increase in side effects in this population.


Tricyclic antidepressants (e.g. amitriptyline, nortriptyline, desipramine) have been shown to provide significant pain relief. Dosing is typically initiated at 10-25mg per day increasing to a daily maximum of 100mg.

Duloxetine, a selective norepinephrine and serotonin reuptake inhibitor, has been effective when used in doses of 60 and 120mg/day. The lower dose is recommended in older patients because of an increase in adverse effects.

Venlafaxine has also been shown to be a valuable agent for painful diabetic neuropathy at doses of 150mg to 225mg daily.


Opioid-like agents

Tramadol is a weak opioid agonist that has shown benefit in diabetic neuropathies. Dosing is 50-100mg per day, or 100-400mg per day using controlled release. It should be used with caution in those taking selective serotonin reuptake inhibitors (SSRIs) and in those with epilepsy.

Opioid analgesics

Morphine, oxycodone, fentanyl and hydromorphone have all been shown to be effective but also present the risk for dependency, tolerance, dose escalation, and diversion.


Cannabinoids such as tetrahydrocannabinol and nabilone have demonstrated efficacy in relieving symptoms from painful diabetic neuropathy in some studies, but limited information is currently available as to optimal dosing.


Several classes of medications can be considered as fourth-line treatments such as SSRIs (citalopram, paroxetine, escitalopram), other anticonvulsants (lacosamide, topiramate, valproic acid), methadone, topical lidocaine and miscellaneous agents (tapentadol).


Combination therapy is an attractive theoretical option as it may reduce the side effect profile if the synergistic effect of the combination allows for a dose reduction of each of the individual medications. More studies are required to determine if this is an effective approach and if so, with which drug combinations.


In addition to pharmacologic management, control of blood glucose plays an essential role in preventing the onset and progression of neuropathy, primarily for those with type 1 diabetes. Nonpharmacological interventions, including physiotherapy, exercise programs, weight loss and psychological treatment modalities, are also essential to enhance outcomes.