James Hughes, MBBS, FRACP
Is gabapentin and nortriptyline combined better than either drug alone for neuropathic pain?
Randomized, controlled, crossover trial. ISRCTN73178636.
Blinded (patients and research nurses).*
6 weeks per treatment.
A university hospital research clinic in Canada.
56 patients (63% men) who had distal, symmetric, sensory, diabetic polyneuropathy (n = 40, median age 61 y) or postherpetic neuralgia with clinician-recorded herpes zoster rash ≥ 6 months before enrollment (n = 16, median age 68 y); daily pain (scores ≥ 4 out of 10) for ≥ 6 months; aspartate and alanine aminotransferase levels ≤ 120% of the upper limit of normal (ULN); serum creatinine level ≤ 150% of ULN; and hemoglobin A1c level < 13%. Exclusion criteria included inherited neuropathy or neuropathy caused by other factors (e.g., hypothyroidism), major organ system disease, cardiovascular autonomic neuropathy, baseline postural hypotension > 20 mm Hg, sedation or ataxia, psychiatric or substance abuse disorders, urinary symptoms related to benign prostatic hypertrophy, and pain caused by another disorder and as severe as neuropathic pain.
3 randomly ordered 6-week treatment periods: 1) gabapentin 3 times daily plus placebo twice daily; 2) nortriptyline twice daily plus placebo 3 times daily; and 3) gabapentin 3 times daily plus nortriptyline twice daily (combination). In each 6-week period, drug doses were titrated to the maximum tolerated dose (MTD) or target ceiling dose (3600 mg gabapentin and 100 mg nortriptyline) on days 1 to 24; continued at that dose on days 25 to 31; tapered on days 32 to 35; and stopped on days 36 to 42 (washout phase).
Mean daily pain intensity (numeric rating scale, from 0 to 10; higher scores = greater pain) over 7 days at MTD and adverse events.
80% (intention-to-treat analysis).
The main results are in the Table. At MTD, dry mouth was less frequent with gabapentin (17%) than nortriptyline (58%) or combined treatment (60%, both P < 0.0001). Groups did not differ for other adverse events at MTD, and no serious adverse events were reported.
Gabapentin and nortriptyline combined was better than either drug alone for relief of neuropathic pain.
Gabapentin (Gab) plus nortriptyline (Nor) vs Nor vs Gab for neuropathic pain†
†MTD = maximum tolerated dose; other abbreviations defined in Glossary. n = 50 for Gab-Nor and Nor groups; n = 46 for Gab group.
‡ Numeric rating scale, from 0 to 10; higher scores = greater pain.
Hughes J. Gabapentin and nortriptyline combined was better than either drug alone for relief of neuropathic pain. Ann Intern Med. 2010;152:JC3–6. doi: 10.7326/0003-4819-152-6-201003160-02006
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Published: Ann Intern Med. 2010;152(6):JC3-6.
Neurology, Neuropathy, Seizure Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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