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 questions

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

*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 grou

This Evidence Summary was originally prepared for the McMaster Optimal Aging Portal.

Published: Monday, August 14, 2017

Please note that the information contained herein is not to be interpreted as an alternative to medical advice from a professional healthcare provider. If you have any questions about any medical matter, you should consult your professional healthcare providers, and should never delay seeking medical advice, disregard medical advice or discontinue medication based on information provided here.

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