title: A short-term double-blind randomized controlled pilot trial with active or placebo pindolol in patients treated with venlafaxine for major depression.
abstract: BACKGROUND
  Pindolol has been widely investigated as an augmenter of antidepressant drug response. Results have been inconsistent. In this study, we used pindolol together with venlafaxine because of its ability to achieve a rapid onset of serotonin transporter blockade.
  
  
  OBJECTIVE
  The object of this study was thus to investigate if pindolol augments the antidepressant response to venlafaxine.
  
  
  METHODS
  Patients with major depression were randomized to either active or placebo pindolol 20 mg retard daily dosage and concomitantly treated with venlafaxine for 19 days. Depression severity was evaluated at four visits. Plasma concentrations of venlafaxine and its major metabolites O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) and pindolol were analysed. The ratio of ODV/venlafaxine was calculated. A low ratio corresponds to patients being poor metabolizers and a high ratio corresponds to patients being extensive metabolizers.
  
  
  RESULTS
  No statistically significant difference in depression outcome was found between treatment groups. A statistically significant effect was, however, found of the ratio of ODV/venlafaxine on depression outcome, showing an augmenting effect of pindolol in patients with a low ratio, and the reverse in patients with a high ratio.
  
  
  CONCLUSIONS
  The differential effect of pindolol, on depression outcome, in patients with varying degrees of venlafaxine metabolism into ODV, corresponds to patients being poor or extensive metabolizers of venlafaxine. From this finding, we conclude that only patients who are poor metabolizers of venlafaxine might benefit from pindolol augmentation. This mechanism might explain some of the variability of outcome in pindolol augmentation studies.
authors.affiliation: Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark. klaus.martiny@regionh.dk
authors.forename: Klaus
authors.initials: K
authors.lastname: Martiny
authors.forename: Marianne
authors.initials: M
authors.lastname: Lunde
authors.forename: Per
authors.initials: P
authors.lastname: Bech
authors.forename: Per
authors.initials: P
authors.lastname: Plenge
mesh_terms: D000328:Adult; D000368:Aged; D003511:Cyclohexanols / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000069468:Desvenlafaxine Succinate; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D010869:Pindolol; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride