The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog

Obstructive steep apnea hypopnea syndrome (OSAHS) is a prevalent disorder, for which there are no universally effective pharmacotherapeutics. We hypot hesized that in OSAHS, excitatory serotoninergic influences are important f or maintaining patency of the upper airway in waking, and that in steep, re duced serotoninergic drive plays a significant role in upper airway collaps e and OSAHS. The previously reported small responses in humans with OSAHS t o serotoninergics may relate, in part, to study design and the drugs/doses selected. We therefore performed multitrials/dose, multidose, randomized sl eep studies testing the effectiveness of a combination of serotoninergics, trazodone, and L-tryptophan, in our animal model of OSAHS, the English bull dog. Trazodone/L-tryptophan caused dose-dependent reductions in respiratory events in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement stee p (REMS). During NREMS, the respiratory disturbance index (RDI) +/- standar d error was 6.3 +/- 1.4 events/h (placebo) and 0.9 +/- 0.3 (highest dose), p < 0.01. During REMS, the RDI was 31.4 +/- 6.1 events/h (placebo) and 11.5 +/- 4.3 (highest dose), p = 0.002. Trazodone/L-tryptophan dose-dependently reduced sleep fragmentation, p = 0.03, increased sleep efficiency, p = 0.0 05, enhanced slow-wave sleep, p = 0.0004, and minimized sleep-related suppr ession of upper airway dilator activity, p < 0.02. Trazodone with L-tryptop han can treat sleep-disordered breathing (SDB) in an animal model of OSAHS; the effectiveness of this therapy may be related to increased upper airway dilator activity in sleep and/or enhanced slow-wave sleep.