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Effects of treatments for symptoms of painful diabetic neuropathy: systematic review

BMJ 2007; 335 doi: (Published 12 July 2007) Cite this as: BMJ 2007;335:87
  1. Man-chun Wong, pain management nurse1,
  2. Joanne W Y Chung, professor2,
  3. Thomas K S Wong, chair professor2
  1. 1Nursing Services Division, United Christian Hospital, 130 Hip Wo Street, Hong Kong
  2. 2School of Nursing, Hong Kong Polytechnic University, Hong Kong
  1. Correspondence to: M C Wong wongmc0829{at}
  • Accepted 13 April 2007


Objective To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy.

Design Systematic review.

Data sources Articles (English and full text) on double blind randomised trials found by searching with the key words anticonvulsant, antidepressant, non-steroidal anti-inflammatory drugs, tramadol, opioid, ion channel blocker, diabetic neuropathy, diabetic peripheral neuropathy, peripheral neuropathy, and neuropathy. The search included Medline, Embase, EMB reviews-AP Journal club, and the Cochrane central register of controlled trials.

Study selection Randomised controlled trials comparing topically applied and orally administered drugs with a placebo in adults with painful diabetic neuropathy.

Data extraction Data were extracted to examine quality of methods, characteristics of studies and patients, efficacy, and side effects. The primary outcome was dichotomous information for 50% or moderate reduction of pain. Secondary outcomes were 30% reduction of pain and withdrawals related to adverse events.

Results Odds ratios were calculated for achievement of 30%, 50%, or moderate pain relief and for withdrawals related to adverse effects. Twenty five reports were included and seven were excluded. The 25 included reports compared anticonvulsants (n=1270), antidepressants (94), opioids (329), ion channel blockers (173), N-methyl-D-aspartate antagonist (14), duloxetine (805), capsaicin (277), and isosorbide dinitrate spray (22) with placebo. The odds ratios in terms of 50% pain relief were 5.33 (95% confidence interval 1.77 to 16.02) for traditional anticonvulsants, 3.25 (2.27 to 4.66) for newer generation anticonvulsants, and 22.24 (5.83 to 84.75) for tricylic antidepressants. The odds ratios in terms of withdrawals related to adverse events were 1.51 (0.33 to 6.96) for traditional anticonvulsants, 2.98 (1.75 to 5.07) for newer generation anticonvulsants, and 2.32 (0.59 to 9.69) for tricylic antidepressants. Insufficient dichotomous data were available to calculate the odds ratios for ion channel blockers.

Conclusion Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy. Oral tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants. Evidence of the long term effects of oral antidepressants and anticonvulsants is still lacking. Further studies are needed on opioids, N-methyl-D-aspartate antagonists, and ion channel blockers.


  • This is version 2 of the paper. Version 1 incorrectly stated that the pooled odds ratio for withdrawal related to adverse events with traditional [rather than newer generation] anticonvulsants was 2.98.

  • Contributors: M-cW planned the review, searched the literature, selected articles, extracted and analysed the data, and drafted and revised the manuscript. JWYC initiated the review, selected articles, and extracted and analysed the data. TKSW supervised the review. All authors approved the final version. M-cW is the guarantor.

  • Funding: None.

  • Competing interests: None declared.

  • Ethical approval: Not needed.

  • Accepted 13 April 2007
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