• Structured Review;
  • Antidepressants;
  • Antinociception;
  • Chronic Pain;
  • Serotonergic;
  • Serotonergic/Noradrenergic;
  • Antinociceptive Effect;
  • Animal Pain Models

Objective.  It has been hypothesized that serotonin reuptake inhibitor antidepressants (ADs) are only weakly antinociceptive but augment noradrenergic (NA) antinociception. Thus, ADs with combined serotonergic (SN) and NA activity, (i.e., the serotonergic/noradrenergic (SN/NA) ADs) should have greater antinociceptive activity versus the NA ADs, which in turn should have more antinociceptive activity than the SN ADs. The objective of this structured review was to test this hypothesis by reviewing relevant basic science literature on the treatment of experimental pain with the above different types of ADs.

Design, Setting, Participants, Outcome, Measures. Animal or human experimental AD pain treatment studies were located by the usual search methods. For animal studies only placebo-controlled studies were included for review. For human studies only double blind placebo-controlled studies were selected for review. The animal and human studies were then sorted according to the pain model represented, e.g., neuropathic pain model. Studies were then characterized according to the type of AD utilized, and the antinociceptive outcome of the AD trial.

Results.  Twenty-two animal studies and 5 human studies fulfilled the inclusion criteria of this structured review. Within the animal nonspecific pain model there were 10 SN/NA AD trials, 9 NA AD trials and 7 SN AD trials. Of these trials 100%, 88.9%, and 14.3% respectfully demonstrated a positive AD antinociceptive effect. Overall, for all the animal models there were 25 SN/NA, 9 NA, and 8 SN trials. Of these trials 92%, 88.9%, and 25% respectfully demonstrated a positive AD antinociceptive effect. For the human pain models, only the SN/NA ADs had been utilized in 7 trials. Here in 42.8% of the trials there was a reported antinociceptive effect.

Conclusions.  Overall, the results of this structured review support the above hypothesis.