Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain

Pain. 2007 Jul;130(1-2):66-75. doi: 10.1016/j.pain.2006.10.029. Epub 2006 Dec 19.


Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95% CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Antidepressive Agents, Tricyclic / administration & dosage*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Chronic Disease
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Nortriptyline / administration & dosage*
  • Nortriptyline / adverse effects
  • Placebos
  • Radiculopathy / drug therapy*
  • Sciatica / drug therapy*
  • Spinal Nerve Roots
  • Treatment Outcome


  • Analgesics, Opioid
  • Antidepressive Agents, Tricyclic
  • Placebos
  • Morphine
  • Nortriptyline