2008 Clinical Practice Guidelines - Canadian Diabetes Association

Table 1. Oral medications for the management of neuropathic pain*
Medication Suggested starting dose † Suggested titration † Common or serious side effects
Tricyclic antidepressants
Amitriptyline
(17,18)
Anticonvulsants
10 mg QHS Increase weekly by 10 mg/day to a
maximum of 150 mg/day
Gabapentin (19) ‡ 300 mg TID Increase weekly by 300 mg/day to
a maximum of 3600 mg/day
Pregabalin (20) 75 mg BID May double weekly to a maximum
of 300 mg BID
Opioid analgesics ‡
Sustained-release
oxycodone (21)
10 mg BID Increase every 3 days by 10 mg to
a maximum of 60 mg BID
Dry mouth
Blurred vision
Constipation
Urinary retention
Dizziness
Drowsiness
Cardiac arrhythmias
(particularly in the elderly)
Dizziness
Somnolence
Ataxia
Fatigue
Peripheral edema
Weight gain
Peripheral edema
Dizziness
Somnolence
Constipation
Nausea
Somnolence
*Clinically important outcomes in the clinical trial setting are generally defined by a 30 to 50% decrease in pain (as assessed by
visual analogue scores). Few patients achieve complete pain relief in these clinical trials.
† Dose ranges are for adults and are generalized from clinical trials – smaller starting doses and slower titration schedules may be
indicated. Optimal doses are the lowest doses required for maximum efficacy without significant side effects. Although required
for some agents, dose adjustments for renal and liver dysfunction are not shown here. Physicians should refer to the most current
edition of the Compendium of Pharmaceuticals and Specialties (Canadian Pharmacists Association, Ottawa, Ontario, Canada) for
product monographs and complete prescribing information.
‡ Combination therapy with gabapentin and an opioid has been shown to achieve better analgesia at lower doses of each drug (22).
RECOMMENDATIONS
1. In people with type 2 diabetes, screening for peripheral
neuropathy should begin at diagnosis of diabetes and
occur annually thereafter. In people with type 1 diabetes,
annual screening should commence after 5 years’ postpubertal
duration of diabetes [Grade D, Consensus].
2. Screening for peripheral neuropathy should be conducted
by assessing loss of sensitivity to the 10-g monofilament
or loss of sensitivity to vibration at the dorsum of
the great toe [Grade A, Level 1 (10)].
3. People with diabetes should be treated with intensified
glycemic control to prevent the onset and progression
of neuropathy [Grade A, Level 1A, for type 1 diabetes
(3,14); Grade B, Level 2 (16), for type 2 diabetes].
4.Antidepressants [Grade A, Level 1A (23,25)], anticonvulsants
[Grade A, Level 1A (19,20,22,28)], opioid analgesics
[Grade A, Level 1A (22)] and topical isosorbide dinitrate
[Grade B, Level 2 (31)] should be considered alone or in
combination for relief of painful peripheral neuropathy.
RELEVANT APPENDIX
Appendix 4: Rapid Screening for Diabetic Neuropathy
REFERENCES
1. Dyck PJ, Kratz KM, Karnes JL, et al.The prevalence by staged
severity of various types of diabetic neuropathy, retinopathy,
and nephropathy in a population-based cohort: the Rochester
Diabetic Neuropathy Study. Neurology. 1993;43:817-824.
2. Partanen J, Niskanen L, Lehtinen J, et al. Natural history of
peripheral neuropathy in patients with non-insulin-dependent
diabetes mellitus. N Engl J Med. 1995;333:89-94.
3. The Diabetes Control and Complications Trial Research
Group. The effect of intensive treatment of diabetes on the
development and progression of long-term complications in
insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:
977-986.
4. Singleton JR, Smith AG, Bromberg MB. Increased prevalence
of impaired glucose tolerance in patients with painful sensory
neuropathy. Diabetes Care. 2001;24:1448-1453.
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COMPLICATIONS AND COMORBIDITIES