Evidence-based data from animal and human experimental studies on pain relief with antidepressants: A structured review

Objective. It has been hypothesized that serotonin reuptake inhibitor antid epressants (ADs) are only weakly antinociceptive but augment noradrenergic (NA) antinociception. Thus, ADs with combined serotonergic (SN) and NA acti vity, (i.e., the serotonergic/noradrenergic (SN/NA) ADs) should have greate r antinociceptive activity versus the NA ADs, which in turn should have mor e antinociceptive activity than the SN ADs. The objective of this structure d review was to test this hypothesis by reviewing relevant basic science li terature on the treatment of experimental pain with the above different typ es of ADs. Design, Setting, Participants, Outcome, Measures. Animal or human experimen tal AD pain treatment studies were located by the usual search methods. For animal studies only placebo-controlled studies were included for review. F or 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 ch aracterized according to the type of AD utilized, and the antinociceptive o utcome of the AD trial. Results. Twenty-two animal studies and 5 human studies fulfilled the inclus ion 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 S N/NA, 9 NA,and 8 SN trials. Of these trials 92%, 88.9%, and 25% respectfull y demonstrated a positive AD antinociceptive effect. For the human pain mod els, 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 abo ve hypothesis.