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Evidence Summary
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Key messages from scientific research that's ready to be acted on
Got It, Hide thisSeveral 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?
Background
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.
Conclusions
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
| Drugs | 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 |
| Mexiletine | 5 trials | No effect | Diarrhea in 9% to 14% of people Nausea in 10% to 36% of people |
| Lacosamide | 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 |
Glossary
nerve pain
A harmless, inactive, and simulated treatment.
Studies where people are assigned to one of the treatments purely by chance.
A comprehensive evaluation of the available research evidence on a particular topic.
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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