This protocol is for patients with diabetes who have distal symmetric polyneuropathy (DSPN) and persistent neuropathic pain that has not responded sufficiently to first-line treatment. Neuropathic pain may be the first symptom prompting patients to seek care and affects a meaningful proportion of individuals with DSPN.
Distal symmetric polyneuropathy with neuropathic pain in a patient with diabetes. The protocol below applies specifically to this sub-population and accounts for the characteristics that make DSPN pain challenging to manage.
Initial treatment with pregabalin, duloxetine, or gabapentin has not achieved the target threshold of at least 30–50% reduction in neuropathic pain. This protocol defines the structured next step after that failure.
The evidence-based next step involves tricyclic antidepressants — a class of agents with established effectiveness for neuropathic pain in diabetes. The full protocol specifies which agents are appropriate, how to individualize the choice, and what clinical goals to monitor. That detail is available in the structured regimen below.
Neuropathic pain may be the first symptom that prompts patients to seek medical care and is present in up to 25% of individuals with DSPN.
Below we summarize the available evidence on the most effective agents for DSPN pain starting with the currently approved drugs and continuing with the other agents based on mechanism of action and strength of evidence.
Although not approved by the U.S. Food and Drug Administration, tricyclic antidepressants are also effective for neuropathic pain in diabetes but should be used with caution given the higher risk of serious side effects.
Venlafaxine, a selective norepinephrine and serotonin reuptake inhibitor, in doses between 150 and 225 mg/day has shown some effectiveness in the treatment of painful DSPN.