Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis

Marcio L. Griebeler, Oscar L. Morey-Vargas, Juan Brito Campana, Apostolos Tsapas, Zhen Wang, Barbara G. Carranza Leon, Olivia J. Phung, Victor Manuel Montori, Mohammad H Murad

Research output: Contribution to journalArticle

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Abstract

Background: Multiple treatments for painful diabetic peripheral neuropathy are available.

Purpose: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.

Data Sources: Multiple electronic databases between January 2007 and April 2014, without language restriction.

Study Selection: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.

Data Extraction: Duplicate extraction of study data and assessment of risk of bias.

Data Synthesis: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.

Limitation: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. Conclusion: Several medications may be effective for short-term

management of painful diabetic neuropathy, although their comparative effectiveness is unclear.

Original languageEnglish (US)
Pages (from-to)639-649
Number of pages11
JournalAnnals of Internal Medicine
Volume161
Issue number9
DOIs
StatePublished - Nov 4 2014

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Diabetic Neuropathies
Tricyclic Antidepressive Agents
Capsaicin
Anticonvulsants
Peripheral Nervous System Diseases
Randomized Controlled Trials
Placebos
Pain
Xerostomia
Amitriptyline
Information Storage and Retrieval
Carbamazepine
Dizziness
Analgesics
Edema
Language
Databases
Network Meta-Analysis
Therapeutics
Serotonin and Noradrenaline Reuptake Inhibitors

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

Pharmacologic interventions for painful diabetic neuropathy : An umbrella systematic review and comparative effectiveness network meta-analysis. / Griebeler, Marcio L.; Morey-Vargas, Oscar L.; Brito Campana, Juan; Tsapas, Apostolos; Wang, Zhen; Carranza Leon, Barbara G.; Phung, Olivia J.; Montori, Victor Manuel; Murad, Mohammad H.

In: Annals of Internal Medicine, Vol. 161, No. 9, 04.11.2014, p. 639-649.

Research output: Contribution to journalArticle

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author = "Griebeler, {Marcio L.} and Morey-Vargas, {Oscar L.} and {Brito Campana}, Juan and Apostolos Tsapas and Zhen Wang and {Carranza Leon}, {Barbara G.} and Phung, {Olivia J.} and Montori, {Victor Manuel} and Murad, {Mohammad H}",
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T2 - An umbrella systematic review and comparative effectiveness network meta-analysis

AU - Griebeler, Marcio L.

AU - Morey-Vargas, Oscar L.

AU - Brito Campana, Juan

AU - Tsapas, Apostolos

AU - Wang, Zhen

AU - Carranza Leon, Barbara G.

AU - Phung, Olivia J.

AU - Montori, Victor Manuel

AU - Murad, Mohammad H

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N2 - Background: Multiple treatments for painful diabetic peripheral neuropathy are available.Purpose: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.Data Sources: Multiple electronic databases between January 2007 and April 2014, without language restriction.Study Selection: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.Data Extraction: Duplicate extraction of study data and assessment of risk of bias.Data Synthesis: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.Limitation: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. Conclusion: Several medications may be effective for short-termmanagement of painful diabetic neuropathy, although their comparative effectiveness is unclear.

AB - Background: Multiple treatments for painful diabetic peripheral neuropathy are available.Purpose: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.Data Sources: Multiple electronic databases between January 2007 and April 2014, without language restriction.Study Selection: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.Data Extraction: Duplicate extraction of study data and assessment of risk of bias.Data Synthesis: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.Limitation: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. Conclusion: Several medications may be effective for short-termmanagement of painful diabetic neuropathy, although their comparative effectiveness is unclear.

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