20141120painfulDMneuropathy

Transcript 20141120painfulDMneuropathy

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.

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*

Minimum effective dose (total daily dose)

50 mg 100 mg 100 mg 50 mg

Class

Topical analgesics

Medication

Capsaicin 0.075%* Doxepin*

Minimum effective dose (total daily dose)

Not predefined Not predefined Lidocaine 5% patch* Not predefined Pentoxifylline* Not predefined Selective serotonin reuptake inhibitors Duloxetine* 60 mg Analgesic opiates Morphine* 15 mg Paroxetine Venlafaxine* 40 mg 75 mg Oxycodone Tapentadol* Tramadol 20 mg 100 mg 100 mg Anticonvulsants Carbamazepine 600 mg Aldose reductase inhibitors* Epalrestat 150 mg Gabapentin Lamotrigine* Oxcarbazepine* Pregabalin Sodium Valproate* Topiramate 900 mg 100 mg 600 mg 150 mg 400 mg 100 mg Ranirestat Fidarestat Ponalrestat Sorbinil 20 mg 1 mg 600 mg 250 mg Other agents Lacosamide* Mexiletine* 100 mg 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。

日

回毎食前メキシチール（メキシレチン）・・・

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）・・・マクロライド系・・・適応外

チャネル遮断薬。適応外その他抗てんかん薬・・・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

Combined direct and indirect estimates. ARI = aldose reductase inhibitor; CrI = credible interval; SMD = standardized mean difference; SNRI = serotonin –norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant.

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.

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。