Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity

Pain. 1999 Nov;83(2):137-45. doi: 10.1016/s0304-3959(99)00082-2.


To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Adult
  • Aged
  • Chronic Disease
  • Diphenhydramine / adverse effects
  • Diphenhydramine / therapeutic use
  • Double-Blind Method
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use
  • Low Back Pain / drug therapy*
  • Low Back Pain / physiopathology*
  • Maprotiline / adverse effects
  • Maprotiline / therapeutic use*
  • Middle Aged
  • Pain Measurement
  • Paroxetine / adverse effects
  • Paroxetine / therapeutic use*
  • Patient Selection
  • Placebos
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*


  • Adrenergic Uptake Inhibitors
  • Hypnotics and Sedatives
  • Placebos
  • Serotonin Uptake Inhibitors
  • Maprotiline
  • Paroxetine
  • Diphenhydramine