To assess the efficacy of
nortriptyline, a
tricyclic antidepressant, as an
analgesic in chronic
back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic
low back pain (
pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or
nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were
pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in
pain intensity scores was significantly greater for participants randomized to
nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of
pain by 22% compared to 9% on placebo. Reduction in disability marginally favored
nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular
pain on
nortriptyline (n = 5) had significantly (P < 0.05) better
analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to
analgesia in
back pain. This modest reduction in
pain intensity suggests that physicians should carefully weigh the risks and benefits of
nortriptyline in chronic
back pain without depression.