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Journal Club
Griebeler ML, Morey-Vargas OL, Brito JP, Tsapas A, Wang Z, Carranza
Leon BG, Phung OJ, Montori VM, Murad MH.
Pharmacologic Interventions for Painful Diabetic Neuropathy: An
Umbrella Systematic Review and Comparative Effectiveness Network
Meta-analysis.
Ann Intern Med. 2014 Nov 4;161(9):639-49.
2014年11月20日 8:30-8:55
８階医局
埼玉医科大学総合医療センター内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田昌文
Matsuda, Masafumi
Drs. Griebeler, Morey-Vargas, Brito, Carranza Leon, and Montori: Department of
Medicine, Division of Diabetes, Endocrinology, Metabolism and Nutrition, Mayo Clinic,
200 First Street SW, Rochester, MN 55905.
Dr. Tsapas: Second Medical Department, Aristotle University, Thessaloniki 54124,
Greece.
Dr. Wang: Knowledge and Evaluation Research Unit, Mayo Clinic, 200 First Street SW,
Rochester, MN 55905.
Dr. Phung: Western University of Health Sciences College of Pharmacy and Western
Diabetes Institute, 309 East Second Street, Pomona, CA 91766-1854.
Dr. Murad: Department of Medicine, Division of Preventive Medicine, Mayo Clinic, 200
First Street SW, Rochester, MN 55905.
Ann Intern Med. 2014 Nov 4;161(9):639-49.
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.
From: Pharmacologic Interventions for Painful Diabetic Neuropathy: An Umbrella Systematic Review and
Comparative Effectiveness Network Meta-analysisPharmacologic Interventions for Painful Diabetic
Neuropathy
Ann Intern Med. 2014;161(9):639-649. doi:10.7326/M14-0511
Figure Legend:
Summary of evidence search and selection.
RCT = randomized, controlled trial.
Date of download: 11/19/2014
Copyright © American College of Physicians. All rights reserved.
Figure 1. Network of RCTs evaluating painful diabetic neuropathy within 3 mo, by
drug class.
Width of the lines is proportional to the number of trials for that comparison. ARI = aldose reductase inhibitor; RCT
= randomized, controlled trial; SNRI = serotonin–norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant.
Class
Medication
Tricyclic antidepressants Amitriptyline
Desipramine*
Imipramine
Nortriptyline*
Selective serotonin
reuptake inhibitors
Anticonvulsants
Minimum
effective dose
(total daily dose)
50 mg
100 mg
100 mg
50 mg
Duloxetine*
60 mg
Paroxetine
Venlafaxine*
40 mg
75 mg
Carbamazepine
600 mg
Gabapentin
Lamotrigine*
Oxcarbazepine*
Pregabalin
Sodium Valproate*
Topiramate
900 mg
100 mg
600 mg
150 mg
400 mg
100 mg
Topical analgesics
Minimum
Medication
effective dose
(total daily dose)
Capsaicin 0.075%* Not predefined
Doxepin*
Not predefined
Lidocaine 5% patch* Not predefined
Pentoxifylline*
Not predefined
Analgesic opiates
Morphine*
15 mg
Oxycodone
Tapentadol*
Tramadol
20 mg
100 mg
100 mg
Epalrestat
150 mg
Ranirestat
Fidarestat
Ponalrestat
Sorbinil
20 mg
1 mg
600 mg
250 mg
Class
Aldose reductase
inhibitors*
Other agents
Lacosamide*
100 mg
Mexiletine*
Not predefined
Dextromethorphan* Not predefined
キネダック（エパルレスタット）・・・アルドース還元酵素を阻害し、疼痛、しびれを抑える。1日3回毎食前
メキシチール（メキシレチン）・・・Naチャネル遮断薬。糖尿病性神経障害に伴う自覚症状（自発痛、しびれ感）の改善
サインバルタ（イミダプリル）・・・SNRI。糖尿病性神経障害の適応あり
ワソラン（ベラパミル）・・・Caチャネル遮断薬。適応外
その他抗てんかん薬・・・適応外
マクロライド系・・・適応外
フロリネフ（酢酸フルドロコルチゾン）・・・適応外
リリカ（プレガバリン）・・・神経障害性疼痛の適応
麻薬系（トラムセット：トラマドール塩酸塩/アセトアミノフェン）
From: Pharmacologic Interventions for Painful Diabetic Neuropathy: An Umbrella Systematic Review and
Comparative Effectiveness Network Meta-analysisPharmacologic Interventions for Painful Diabetic
Neuropathy
Figure Legend:
Summarized risk of bias, by domains in the included RCTs.
RCT = randomized, controlled trial.
Ann Intern Med. 2014;161(9):639-649. doi:10.7326/M14-0511
Date of download: 11/19/2014
Copyright © American College of Physicians. All rights reserved.
From: Pharmacologic Interventions for Painful Diabetic Neuropathy: An Umbrella Systematic Review and
Comparative Effectiveness Network Meta-analysisPharmacologic Interventions for Painful Diabetic
Neuropathy
Ann Intern Med. 2014;161(9):639-649. doi:10.7326/M14-0511
Figure Legend:
Agents for treatment of diabetic peripheral neuropathy compared with placebo, by class.
Combined direct and indirect estimates. ARI = aldose reductase inhibitor; CrI = credible interval; SMD = standardized mean
difference; SNRI = serotonin–norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant.
Date of download: 11/19/2014
Copyright © American College of Physicians. All rights reserved.
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 headto-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.
Primary Funding Source: Mayo Foundation for
Medical Education and Research.
Message
65件の無作為化試験（被験者1万2632人、介入27
種）を対象に、糖尿病性末梢神経障害における
鎮痛薬の疼痛緩和効果を包括的システマティッ
クレビューとネットワークメタ解析で検証。セ
ロトニン・ノルアドレナリン再取り込み阻害薬
（SNRI）、カプサイシン、三環系抗うつ薬
（TCA）などでプラセボに比べ短期疼痛緩和効果
が増加した。

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