Clinical summary of the Canadian Pain Society's (CPS) revised consensus statement on the pharmacologic management of neuropathic pain.

Overview
Neuropathic pain, arising from somatosensory system damage, is frequently encountered in primary care.
Aging, obesity, and improved cancer survival rates contribute to rising neuropathic pain cases, notably postherpetic neuralgia and painful diabetic neuropathy.
This is a clinical summary of the Canadian Pain Society's (CPS) revised consensus statement on the pharmacologic management of neuropathic pain.


I. First-Line Agents: Gabapentinoids, Tricyclic Antidepressants (TCAs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

II. Second-Line Agents: Tramadol and Opioids

III. Third-Line Agents: Cannabinoids

IV. Fourth-Line Agents: These options have less robust evidence or are reserved for specific situations: Methadone, other Anticonvulsants: (Lamotrigine, Lacosamide), Tapentadol, topical Lidocaine or Botulinum Toxin.

Important Considerations:

Combination Therapy: Combining agents from different classes may enhance pain relief.

Off-Label Use: Many of these medications are used off-label for Neuropathic pain.

 

 

 

Table 2. Selected neuropathic analgesic dosing regimens
AGENT	INITIAL DOSE	TITRATION	DOSE RANGE	ADVERSE EFFECTS	ADDITIONAL INFORMATION
Anticonvulsants
• Gabapentin	100-300 mg/d	Increase by 100-300 mg/d every wk	300-1200 mg 3 times/d	Drowsiness, dizziness, peripheral edema, visual blurring	Dosage adjustments required in renal failure and in elderly patients
• Pregabalin	25-150 mg/d	Increase by 25-150 mg/d every wk	150-300 mg	Drowsiness, dizziness, peripheral edema, visual blurring	Similar adjustments in renal failure
			twice daily
• Carbamazepine	100 mg/d	Increase by 100-200 mg/d every wk	200-400 mg 3 times/d	Drowsiness, dizziness, blurred vision, ataxia, headache, nausea, rash	Drug of first choice for idiopathic trigeminal neuralgia; as an enzyme inducer, it might interfere with activity of other drugs such as warfarin; monitoring of blood counts and liver function recommended
TCAs
• Amitriptyline, nortriptyline, or desipramine	10–25 mg/d	Increase by 10 mg/d every wk	10-100 mg/d	Drowsiness, confusion, orthostatic hypotension, dry mouth, constipation, urinary retention, weight gain, arrhythmia	Amitriptyline more likely to produce drowsiness and anticholinergic side effects; contraindicated in patients with glaucoma, symptomatic prostatism, and substantial cardiovascular disease
SNRIs
• Venlafaxine	37.5 mg/d	Increase by 37.5 mg/d every wk	150-225 mg/d	Nausea, dizziness, drowsiness, hyperhidrosis, hypertension	Dosage adjustments required in renal failure
• Duloxetine	30 mg/d	Increase by 30 mg/d every wk	60-120 mg/d	Sedation, nausea, constipation, ataxia, dry mouth	Contraindicated in patients with glaucoma
Controlled-release opioids*
• Morphine	15 mg every 12 h	NA	NA	Nausea, vomiting, sedation, dizziness, urinary retention, constipation	Constipation requires concurrent bowel regimen; monitor for overdose, effectiveness, tolerance, dependence, and appropriateness
• Oxycodone	10 mg every 12 h	NA	NA
• Fentanyl	12 µg/h (patch)	NA	NA
• Hydromorphone	3 mg every 12 h	NA	NA
Others
• Tramadol	50 mg/d	Increase by 50 mg/d every wk	50-100 mg 4 times/d or 100-400 mg/d (controlled release)	Ataxia, sedation, constipation, seizures, orthostatic hypertension	Might lower seizure threshold; use with caution in patients with epilepsy
• Tapentadol (controlled release)	50 mg every 12 h	Increase by 50 mg/ dose every wk	Maximum dose 500 mg in 24 h	Nausea, constipation, somnolence, dizziness, vomiting, fatigue	Contraindicated in patients with creatinine clearance < 0.5 mL/s/m2 and Child-Pugh class C. Caution in those at risk of seizure
• Lidocaine	NA	NA	5% patches or gel applied to painful areas for 12 h in a 24-h period	NA	Most useful for postherpetic neuralgia; has virtually no systemic side effects; lidocaine patches not available in Canada
• THC or nabiximols	1-2 sprays every 4 h, maximum 4 sprays on day 1	NA	2 sprays 4 times/d	Dizziness, fatigue, nausea, euphoria	Approved in Canada for neuropathic pain associated with multiple sclerosis; causes positive urine drug test results for cannabinoids; monitor application site (oral mucosa)
• Nabilone	0.25–0.5 mg at night (owing to side effects of drowsiness and fatigue)	Increase by 0.5 mg/d every wk	3 mg twice daily	Dizziness, drowsiness, dry mouth	Approved in Canada for nausea and vomiting associated with chemotherapy. Does not cause positive test results for cannabinoids on routine urine drug testing
NA—not available, SNRI—serotonin-norepinephrine reuptake inhibitor, TCA—tricyclic antidepressant, THC—tetrahydrocannabinol. *Opioid initial dosing recommendations are for healthy opioid-naïve adults; opioid titration and dose range are not included owing to variability of patient and pain factors. Adapted with permission from Moulin et al.7

 

Reference:
Canadian Pain Society consensus - Pharmacologic management of chronic neuropathic pain