Antidepressants for the Relief of Chronic Pain: Do They Work?

A selective, critical review of heterocyclic antidepressant trials for chronic, benign pain syndromes is reported. The first two sections consider 46 trials for chronic pain syndromes, excluding chronic low back pain. The first section discusses 32 trials that failed to meet minimal design and protocol criteria; the second section discusses the remaining 14 trials meeting minimal criteria. These trials were criticized according to four types of validity criteria: statistical conclusion validity, internal validity, construct validity, and external validity. No trial met all four validity requirements, and three failed to meet any. Some evidence was found for the efficacy of low-dose antidepressants for chronic headache. The third section focuses exclusively on chronic low back pain. Seven trials are reviewed, of which only two met minimal design and protocol criteria. Both of these failed to convincingly demonstrate an effect. It is concluded that the efficacy of heterocyclic antidepressants for chronic low back pain and syndromes other than headache remains unproven. Directions recommended for future research include using the newer, non-tricyclic drugs; wider dose ranges; larger, more representative samples; and reliable, valid, comprehensive dependent variables submitted to simultaneous, planned statistical analyses controlling for potential confounds.