POSSIBLE BIOLOGICAL MECHANISMS OF THE SEROTONIN REUPTAKE INHIBITOR DISCONTINUATION SYNDROME

Although the number of documented serotonin reuptake inhibitor (SRI) d iscontinuation reactions is increasing, to date no systematic studies have been completed; therefore the mechanism of action for these react ions is not clearly understood. However, several hypotheses have been proposed. Researchers have postulated that discontinuation events resu lt from a sudden decrease in the availability of synaptic serotonin in the face of down-regulated serotonin receptors. In addition, other ne urotransmitters, such as dopamine, norepinephrine, or gamma-aminobutyr ic acid (GABA), may also be involved, although little research in this area has been published. Individual patient sensitivity, i.e., geneti cs or cognitive mindset, may also be a factor in SRI discontinuation p henomena. Finally, experts have hypothesized that since some symptoms associated with paroxetine withdrawal are similar to those of tricycli c antidepressant discontinuation, they may be caused by cholinergic re bound.