title: The 'dalhousie serotonin cocktail' for treatment-resistant major depressive disorder.
abstract: We describe the successful treatment of five patients with treatment-resistant major depressive disorder (TR-MDD) with a combination pharmacotherapy of pindolol, tryptophan and nefazodone. Five TR-MDD outpatients who had previously not responded to at least four different antidepressant medication trials were initiated on 300 mg/day of nefazodone, 7.5 mg/day of pindolol and 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 (HAM-D) was used to evaluate outcome. By week 4, all cases demonstrated at least 50% decrease in HAM-D scores. At the end of the trial, the group mean 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 results suggest that if serotonin availability and release is further enhanced by 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 successful efficacy rate of this preliminary study, controlled studies are required to confirm the efficacy of this treatment strategy.
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. sdursun@is.dal.ca
authors.forename: S M
authors.initials: SM
authors.lastname: Dursun
authors.forename: S
authors.initials: S
authors.lastname: Devarajan
authors.forename: S
authors.initials: S
authors.lastname: Kutcher
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000627:therapeutic use*; D010879:Piperazines; D011569:Psychiatric Status Rating Scales; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D014364:Tryptophan / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D014230:Triazoles; C051752:nefazodone; D014364:Tryptophan; D010869:Pindolol