OBJECTIVE: To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life.
METHODS: We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE).
RESULTS: We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects.
CONCLUSIONS: For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.
How depressing that a common condition which causes so much distress has such a poor evidence base to choose treatment. We just keep best guessing and doing n=1 trials, I suppose.
This is a well done analysis and review of a poorly studied subject-especially long term.
Pain reduction and QOL improvement in patients with DPN is a challenging job. The number of approved drugs can be used. Of course, they are better than placebo but efficacy, acceptability and adverse effects of individual molecule differ from patient to patient. In practice, a physician may choose a drug or in combination on the individualized basis. According to my practice, SNRIs; duloxetine and venlafaxine were found comparatively better in terms of efficacy and adverse effects compared to rest of the approved drugs.
This is a good overall review of the lit. It reinforces what is already out in the literature.
As the authors point out, there are multiple limitations for this study of studies. However since treatment is so difficult, if there are a couple treatments that stand even a bit above the others they are probably worth knowing about.