A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain

Abstract

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 Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects.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.

Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression

“…Despite some progress, clinical treatment of pain and depression has so far been limited to symptomatic management (3, 36). A number of studies have also suggested that the effect of antidepressants on chronic pain is not necessarily related to their anti-depression property (36)(37)(38).…”

Efficacy of Antidepressants as Analgesics: A Review

“…87 Studies with amitryptiline, nortriptyline, and maprotiline demonstrated analgesic ESs ranging from 0.45 to 0.64. [88][89][90] A meta analysis by Salerno and colleagues revealed that antidepressants had a small but statistically significant effect in reducing LBP when compared with placebo. Patients treated with antidepressants experienced a small but significant improvement of 0.41 (95% confidence interval [CI], 0.22-0.61) in the standardized mean difference for pain severity.…”

Exacerbated mechanical allodynia in rats with depression-like behavior

“…While antidepressants affect mood changes in chronic pain patients, they do not always improve outcome measures of clinical pain (Littlejohn, Guymer, 2006;Carter 2002). In this regard, several studies have suggested that the effect of antidepressants on chronic pain may not be related to their antidepression property (Atkinson et al, 1998;Collins et al2000;Max et al, 1987;Mico et al, 2006;Sharav et al, 1987). To date, the relationship between pain and depression remains unclear.…”