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Several drugs reduce pain related to diabetic neuropathy in the short-term

Griebeler ML, Morey-Vargas OL, Brito JP, et al. Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis. Ann Intern Med. 2014;161:639-49.

Review question

In adults with painful neuropathy due to diabetes, which drugs best relieve pain?


People with diabetes can get neuropathy. Symptoms of diabetic neuropathy can include pain, most often felt in the legs and feet. Diabetic neuropathy cannot be cured, but oral drugs and topical drugs can reduce the pain. Different drugs have different side effects.

How the review was done

The researchers did a systematic review, searching for studies that were published up to April 2014.

They found 65 randomized controlled trials with 12,632 people (mostly men). The average age was 46 to 65 years.

The key features of the studies were:

  • people were at least 18 years of age and had painful diabetic neuropathy;
  • most drugs were compared with placebo and given for 12 weeks or less; and
  • studies that used combinations of drugs were excluded.

Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

What the researchers found

At 3 months or less:

  • anticonvulsants, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, and topical capsaicin reduced pain more than placebo; and
  • serotonin–norepinephrine reuptake inhibitors reduced pain more than anticonvulsants, opioids, or mexiletine.

Few trials assessed drugs taken for more than 3 months. Of those that did, anticonvulsants taken for up to 22 weeks reduced pain more than placebo.

Side effects of drugs varied.


In people with painful diabetic neuropathy, anticonvulsants, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, and topical capsaicin reduce pain at up to 3 months. Serotonin–norepinephrine reuptake inhibitors work better than anticonvulsants.

Drugs for reducing pain at up to 3 months in painful diabetic neuropathy


Number of trials*

Effect of drugs on pain

Side effects of drugs reported in more than 1 trial†

Anticonvulsants (pregabalin, gabapentin, lamotrigine, oxcarbazepine, topiramate, valproic acid, carbamazepine)

14 trials

Reduced pain more than placebo overall

Carbamazepine reduced pain more than placebo

Diarrhea in 11% to 12% of people

Dizziness in to 2.5% to 53% of people

Drowsiness in 3% to 40% of people

Fatigue in 4% to 16% of people

Headache in 8% to 21% of people

Nausea in 2.4% to 41% of people

Swelling of arms, legs, hands, or feet in 3.8% to 17% of people

Rash in 4% to 15% of people

Serotonin–norepinephrine reuptake inhibitors (duloxetine, venlafaxine)

7 trials

Reduced pain more than placebo overall

Reduced pain more than anticonvulsants, opioids, and mexiletine overall

Duloxetine and venlafaxine each reduced pain more than placebo

Constipation in 7% to 19% of people

Dizziness in 6% to 25% of people

Drowsiness in 8% to 28% of people

Upset stomach in 9% to 10% of people

Nausea in 10% to 32% of people

Opioids (oxycodone, tapentadol)

4 trials

No effect

Constipation in 6% to 59% of people

Drowsiness in 6.3% to 41% of people

Nausea in 12% to 73% of people

Tricyclic antidepressants (imipramine, amitriptyline, desipramine)

3 trials

Reduced pain more than placebo overall

Amitriptyline reduced pain more than placebo

Dry mouth in 32% to 89% of people


5 trials

No effect

Diarrhea in 9% to 14% of people

Nausea in 10% to 36% of people


1 trial

No effect

Dizziness in 5.7% to 28% of people

Fatigue in 12% to 15% of people

Nausea in 4% to 18% of people

Topical capsaicin

3 trials

Reduced pain more than placebo

Burning of the skin where applied in 54% to 63% of people

*Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

†Includes trials with treatment longer than 3 months. Adverse effects may vary for individual drugs within a drug group.


nerve pain
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.
Topical drug
A drug that is applied to a specific area on the skin (or other surface on the body, such as the eye). It can be a cream, lotion, gel, ointment, patch, or some other form.

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