katie marchington

8/7/2019 katie marchington

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Treating Diabetic Neuropathic

Pain

Am Fam Physician. 2010;82(2):151-158.

Katie Marchington PGY-2


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Treating Diabetic Neuropathic Pain

Why is it important?

Diagnosis

Goals of treatment Management options

General principles

Pharmacotherapy

Alternative therapies


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Diagnosis

Hx:

Burning, tingling or aching discomfort in distalextremities that is worse at night

Loss of sensation

P/e:

Loss of sensitivity to 10 g monofilament orvibration of 128 Hz tuning fork in a symmetricalstocking glove distribution starting distally andprogressing proximally

+/- allodynia, hyperalgesia


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Goals of treatment

Although complete pain relief is ideal, pain

reduction of 30 to 50% can be expected in

most patients on maximal pharmacotherapy


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Management: General Principles

Intensive glycemic control is effective for the

primary prevention or secondary intervention

of neuropathy in patients with T1DM and

primary prevention in patients with T2DM


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Management: Pharmacotherapy

TCAs

Anticonvulsants

SSRIs and SNRIs Opiates and Opiate-like medication

Topical medications


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Tricyclic Antidepressants

When to use: First line

Dose: nortriptyline 25 to 50 mg (150mg) hs, oramitriptyline 25 to 150 mg (150 mg) hs

Covered by ODB? Yes (no LU code)

Advantages:

Affordable

Cochrane review of TCAs for treating neuropathicpain revealed an overall effectiveness, with anNNT of 1.3 (based on 5 studies)


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Tricyclic Antidepressants, continued

Disadvantages

1 in 5 patients discontinue this medicationbecause of adverse effects

S/e: dry mouth, somnolence, dizziness,constipation

CI: recent cardiac events (MI, CHF) or arrhythmias(QT prolongation)

Caution: narrow-angle glaucoma, BPH,orthostasis, urinary retention, impaired liverfunction, or thyroid disease due to anti-cholinergiceffect


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New Anticonvulsants

(pregabalin, gabapentin)

When to use: First-line ifthere arecontraindications or an inadequate response toTCAs

Dose: pregabalin 150 to 600 mg divided bid-tid,gabapentin 300 to 1,200 mg tid

Covered by ODB? Yes, but only if: ineffective response or intolerable side

effects/contraindications to adequate trials of a TCA(and gabapentin for pregabalin)

Requires application to and approval from ExceptionalAccess Program


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New Anticonvulsants

(pregabalin, gabapentin), continued

Advantages: Gabapentin: 2005 Cochrane review evaluating the use of

gabapentin in painful neuropathy (diabetic and mixedneuralgia) calculated a combined NNT of 4.3

Gabapentin: few drug interactions Pregabalin: 2008 meta-analysis of seven trials, 1,510

diabetic neuropathic pain patients, showed pregabalin tobe effective with a dose-related response

Disadvantages: Expensive Gabapentin s/e: dizziness, somnolence, headache,

diarrhea

Pregabalin s/e: dizziness, somnolence, edema, weight gain


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Old anticonvulsants (carbamazepine)

When to use: 2nd line alternative to otheranticonvulsants

Dose: 200 to 600 mg twice per day

Covered by ODB? Yes (LA formulation requires LUcode)

Advantages:

One Cochrane review examined 12 studies including404 participants with a variety of types of neuropathicpain found an NNT of 2.5 to achieve moderate painrelief


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Old anticonvulsants (carbamazepine),

continued

Disadvantages:

S/e: drowsiness, dizziness, constipation, nausea,

and ataxia

Rare: toxic epidermal necrolysis and Stevens-

Johnson syndrome.

Before initiating: CBC, reticulocyte count, LFTs,

urea, Cr, and iron levels, UA q6-12 mo: lipid panel and drug level


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SNRIs (and SSRIs)

When to use: SNRIs: 2nd or 3rd line

SSRIs: 3rd line

Dose: venlafaxine 150 to 225 mg per day, duloxetine 60to 120 mg per day

Covered by ODB? Yes (no LU code)

Advantages: better tolerated and have fewer drug interactions than

TCAs 2007 Cochrane review examined three studies of

venlafaxine for neuropathic pain, revealing an NNT of 3.1

Duloxetine: 2006 RCT revealed a NNT of 5.1, but did notfollow patients who dropped out of the study


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SNRIs (and SSRIs), continued

Disadvantages

S/e venlafaxine: somnolence, insomnia, sweating,

dyspepsia

S/e duloxetine: nausea, headache, constipation,

fatigue

Further studies are needed to investigate the

effectiveness of venlafaxine for diabetic peripheralneuropathic pain specifically

SSRIs: more high-quality studies are needed


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Opiates and Opiate-like medications

(Tramadol) When to use: 4th line, for patients who do not achieve pain

relief goals with other therapies

Dose: e.g. morphine 15 to 120 mg per day, tramadol 200 to400 mg per day

Covered by ODB? most opiates: Yes (no LU code)

tramadol or tramacet: NOTcovered

Advantages: 2006 Cochrane review: nine 28 d studies showed benefit over

placebo for methadone, levorphanol, morphine, and controlled-release oxycodone for general neuropathic pain

2006 Cochrane review: Tramadol had a NNT 3.8 to achieve 50percent pain reduction in general neuropathic pain


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Opiates and Opiate-like medications

(Tramadol), continued

Disadvantages:

Pain reduction with opiates only modest, 20-30%

S/e opiates: nausea, constipation, somnolence,dizziness

S/e tramadol: nausea, constipation, somnolence,

headache

Tramadol lowers seizure threshold and thereforeshould be avoided in patients with epilepsy or risk

of seizure


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Topical medications

When to use: can be added to systemic therapy at any time

Dose:

capsaicin cream 0.075% topical cream four times per day

lidocaine 5% patches: up to three patches per day, each patch worn upto 12 hours

Covered by ODB?

Capsaicin cream: No

Lidocaine 2% ointment/lotion: Yes (no LU code); 5% gel or cream canbe made at compounding pharmacy but not covered, patch notavailable in Canada

Advantages: Capsaicin: 2004 meta-analysis involving six trials of 656 patients had

an NNT of 6.4 for 50 percent pain reduction at four weeks

Lidocaine: one small RCT in 2003 revealed an NNT of 4.4 for 50percent pain reduction


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Topical medications, continued

Disadvantages:

S/e for both: skin irritation


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Management: Complementary

Alternative Medicine

L-carnitine, alpha-lipoic acid (OTCs),

acupuncture

Some small studies show positive results, more data are

needed


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Combination therapy

One study showed a decreased need for opiateswhen combined with gabapentin

Otherwise advisable to exhaust monotherapy,

and access specialist help due to complicateddrug interaction profiles

Always avoid combining TCAs with SSRIs or SNRIsbecause of risk of serotonin syndrome

Drugs that may interact with diabetic peripheralneuropathic pain therapies include statins, betablockers, sulfonylureas, levothyroxine, warfarinand loop diuretics


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Summary

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