The 'Dalhousie Serotonin cocktail' for treatment-resistant major depressive disorder

We describe the successful treatment of five patients with treatment-resist ant major depressive disorder (TR-MDD) with a combination pharmacotherapy o f pindolol, tryptophan and nefazodone. Five TR-MDD outpatients who had prev iously not responded to at least four different antidepressant medication t rials were initiated on 300 mg/day of nefazodone, 7.5 mg/day of pindolol an d 1 g/day of tryptophan. Pindolol doses remained the same throughout the 20 weeks, while tryptophan and nefazodone dosages were gradually increased to 8 g/day and 450 mg/day, respectively. The Hamilton Depression Rating Scale CHAM-IP) was used to evaluate outcome. By week 4, all cases demonstrated a t least 50% decrease in HAM-D scores. At the end of the trial, the group me an HAM-D score had significantly decreased from 26.8 (+/- 1.9) to 1.8 (+/- 0.8) (p < 0.001). No significant adverse effects were reported. These resul ts suggest that if serotonin availability and release is further enhanced b y tryptophan in the presence of nefazodone and pindolol, an antidepressant effect may be produced in patients who are otherwise. treatment-resistant. Due to limited sample: size, an open design and an 'unusually' high success ful efficacy rate of this preliminary study, controlled studies are require d to confirm the efficacy of this treatment strategy.