Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin

Figures & data

Table 1 Odds ratios for efficacy and withdrawal, numbers needed to treat (NNT) and numbers needed to harm (NNH)

Drug class	Odds ratio – efficacy	Odds ratio – withdrawal (2ry to AE)	NNT	NNH
Tricyclics	22.2 (5.8–84.7)	2.3 (0.6–9.7)	1.5–3.5	2.7–17.0
Duloxetine	2.6 (1.6–4.8)	2.4 (1.1–5.4)	5.7–5.8	15.0
Traditional anticonvulsants	5.3 (1.8–16.0)	1.5 (0.3–7.0)	2.1–3.2	2.7–3.0
New generation anticonvulsants	3.3 (2.3–4.7)	3.0 (1.75–5.1)	2.9–4.3	26.1
Opioids	4.3 (2.3–7.8)	4.1 (1.2–14.2)	2.6–3.9	9.0

Note: Copyright © 2010, The Endocrine Society. Reproduced with permission from Vinik A. The approach to the management of the patient with neuropathic pain. J Clin Endocrinol Metab. 2010;95:4802–4811.⁷⁰

Abbreviation: 2ry to AE, secondary to adverse events.

Figure 1 Efficacy analysis of drugs used for painful diabetic neuropathy.

Note: Copyright © 2012, MDTEXT.COM, INC. Reproduced with permission from Endotext.org [homepage on the internet]. Darmouth: Chapter 31 – Diabetic Neuropathies; 2012 version [updated September 26, 2012]. Available from: http://www.endotext.org/diabetes/diabetes31/diabetesframe31.htm. Accessed December 12, 2012.¹⁵⁴

Table 2 Summary of American Academy of Neurology recommendations

Evidence level	Recommended	Not recommended
Level A	Pregabalin 300–600 mg/day	Oxcarbazepine
Level B	Gabapentin 900–3600 mg/day	Lamotrigine
	Duloxetine 60–120 mg/day	Lacosamide
	Amitriptyline 25–100 mg/day	Clonidine
	Venlafaxine 75–225 mg/day	Pentoxifylline
	Sodium valproate 500–1200 mg/day	Mexiletine
	Dextromethorphan 400 mg/day	Magnetic field treatment
	Morphine titrated to 120 mg/day	Low-intensity laser therapy
	Tramadol 210 mg/day	Reiki therapy
	Oxycodone 37 mg/day (max 120 mg/day)
	Capsaicin, 0.075% QID
	Isosorbide dinitrate spray
	TENS × 3–4

Note: Copyright © 2011, Wolters Kluwer Health. Reprinted with permission from Bril V, England J, Franklin GM, et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76:1758–1765.¹⁵

Abbreviations: QID, four times a day; TENS, transcutaneous electrical nerve stimulation.

Table 3 Treatment options for symptomatic diabetic polyneuropathy pain dosing and side effects

Drug class	Drug	Dose (mg)	Side effects
Tricyclics	Amitryptyline	50–150 QHS	Somnolence, dizziness, dry mouth, tachycardia
	Nortriptyline	50–150	QHS Constipation, urinary retention, blurred vision
	Imipramine	25–150 QHS	Confusion
	Desipramine	25–150 QHS
SSRIs	Paroxetine	40 QD	Somnolence, dizziness, sweating, nausea, anorexia
	Citalopram	40 QD	Diarrhea, impotence, tremor
SNRIs	Duloxetine	60 QD	Nausea, somnolence, dizziness, anorexia
Anticonvulsants	Gabapentin	300–1200 TID	Somnolence, dizziness, Confusion, ataxia
	Pregabalin	50–150 TID	Somnolence, confusion, edema, weight gain
	Carbamazepine/oxcarbazepine	Up to 200 QID	Dizziness, somnolence, nausea, leukopenia
	Topiramate	Up to 400 QD	Somnolence, dizziness, ataxia, tremor
Opioids	Tramadol	50–100 BID	Nausea, constipation, somnolence
	Oxycodone CR	10–30 BID	Somnolence, nausea, constipation
Topical	Capsaicin	0.075% QID	Local irritation
	Lidocaine	0.04% QD	Local irritation
Injection	Botulinum toxin		None

Note: Copyright © 2010, The Endocrine Society. Reproduced with permission from Vinik A. The approach to the management of the patient with neuropathic pain. J Clin Endocrinol Metab. 2010;95:4802–4811.⁷⁰

Abbreviations: QHS, at bedtime; QD, once a day; QID, four times a day; TID, three times a day; BID, twice a day; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin–norepinephrine reuptake inhibitors.

Table 4 Treatment algorithm for painful diabetic peripheral neuropathy (Toronto Consensus Panel on Diabetic Neuropathy)

Painful diabetic neuropathy
First line	α2-δ agonist (pregabalin or gabapentin)	SNRI (duloxetine)	TCA
If pain control is inadequate and considering contraindications
Second line	TCA or SNRI	TCA or α2-δ agonist (pregabalin or gabapentin)	SNRI or α2-δ agonist (pregabalin or gabapentin)
If pain control is still inadequate
Third line	Add opioid agonist as combination therapy

Note: Copyright © 2011, John Wiley and Sons. Adapted with permission from Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–638.⁷²

Abbreviations: SNRI, serotonin–norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant.

Table 5 Tailoring treatment to the patient (Toronto Consensus Panel on Diabetic Neuropathy)

Comorbidities	Contraindications
Glaucoma	TCAs
Orthostatic hypotension	TCAs
Cardiovascular disease	TCAs
Hepatic disease	Duloxetine
Edema	Pregabalin, gabapentin
Unsteadiness and falls	TCAs
Weight gain	TCAs, pregabalin, gabapentin
Other factors: cost	Duloxetine, pregabalin

Note: Copyright © 2011, John Wiley and Sons. Adapted with permission from Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–638.⁷²

Abbreviation: TCAs, tricyclic antidepressants.

Figure 2 Changes in SF-36 domain scores grouped according to extent of pain relief in patients treated with pregabalin.

Notes: Only SF-36 domains that exhibited significant improvement in response to pregabalin treatment, compared to placebo, are shown. Reprinted from The Journal of Pain. Vinik A, Zlateva G, Cheung R, Murphy K, Emir B, Whalen E. Understanding the impact of pain response on changes in function, quality of life, and sleep interference in patients with painful diabetic peripheral neuropathy and post-herpetic neuralgia treated with pregabalin. 2010;11:S17. Copyright 2010 with permission from Elsevier.²⁰

Figure 3 Mediational analysis model, illustrating that the change in SF-36 domain score (overall treatment effect) may be due to a direct effect of pregabalin on that particular SF-36 domain (direct effect) or may be mediated through pregabalin-driven pain relief or improvements in sleep (indirect effects).

Note: Reprinted from The Journal of Pain. Vinik A, Zlateva G, Cheung R, Murphy K, Emir B, Whalen E. Understanding the impact of pain response on changes in function, quality of life, and sleep interference in patients with painful diabetic peripheral neuropathy and post-herpetic neuralgia treated with pregabalin. 2010;11:S17. Copyright 2010 with permission from Elsevier.²⁰

Figure 4 Treatment algorithm: neuropathic pain after exclusion of non-diabetic etiologies and stabilization of glycemic control.

Note: Copyright © 2010, The Endocrine Society. Reproduced with permission from Vinik A. The approach to the management of the patient with neuropathic pain. J Clin Endocrinol Metab. 2010;95:4802–4811.⁷⁰
Abbreviations: IVIg, intravenous immunoglobulin; SNRI, serotonin-noradrenaline reuptake inhibitors; TCA, tricyclic antidepressants.

Vinik A The approach to the management of the patient with neuropathic pain J Clin Endocrinol Metab 2010 95 4802 4811 21051576

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Endotext.org [homepage on the internet] Darmouth: Chapter 31 – Diabetic Neuropathies 2012 version [updated September 26, 2012]. Available from: http://www.endotext.org/diabetes/diabetes31/diabe-tesframe31.htm Accessed December 12, 2012

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Bril V England J Franklin GM Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation Neurology 2011 76 1758 1765 21482920

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Tesfaye S Vileikyte L Rayman G Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management Diabetes Metab Res Rev 2011 27 629 638

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Vinik A Zlateva G Cheung R Murphy K Emir B Whalen E Understanding the impact of pain response on changes in function, quality of life, and sleep interference in patients with painful diabetic peripheral neuropathy and post-herpetic neuralgia treated with pregabalin J Pain 2010 11 S17

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