Differential effects of two types of antidepressants, amitriptyline and fluoxetine, on anorectal motility and visceral perception

Purpose to assess the effects of 2 types of antidepressants (tricyclic, serotoninergic) on anorectal motility and visceral perception. Methods : placebo‐controlled, randomized, double‐blind, crossover study performed in 12 healthy male volunteers who received a single oral dose of amitriptyline (80 mg), fluoxetine (40 mg) or a placebo. Drug effects were assessed using phasic isobaric distension of the rectum with an electronic barostat (11 levels from 1 to 51 mm Hg) 3‐4 h after drug intake. Rectal volume and pressure, pressures at upper and lower parts of anal canal, rectal defecation (5–level scale) and pain (visual analogue scale) perceptions were recorded at each level of pressure. Results : Ten subjects completed the study. Compared to placebo, neither amitriptyline nor fluoxetine modified maximal rectal volume and pressure and rectal perceptions. Compared to placebo, antidepressants significantly reduced mean and residual pressures at upper part of anal canal (−18%, P =0.0019, and −27%, P =0.0002, respectively, for amitriptyline; −26%, P =0.0001, and −33%, P =0.0001, respectively, for fluoxetine) whereas only amitriptyline significantly reduced mean pressure at lower part of anal canal (−16%, P =0.0008). Conclusions : both antidepressants similarly relax internal anal sphincter, probably through a non‐specific mechanism, without modifying visceral perception. Only amitriptyline relaxes external anal sphincter suggesting specific noradrenergic alteration of motor‐somatic reflex. Clinical Pharmacology & Therapeutics (2004) 75 , P10–P10; doi: 10.1016/j.clpt.2003.11.037