Paroxetine and pindolol: a randomized trial of serotonergic autoreceptor blockade in the reduction of antidepressant latency

Int Clin Psychopharmacol. 1997 Mar;12(2):81-9.


A double-blind, randomized, placebo-controlled, parallel group study was performed in 80 adult outpatients meeting ICD-10 criteria for major depression and with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 18 at baseline. All patients received paroxetine (20 mg once a day) plus either pindolol (2.5 mg three times a day) or matching placebo for 6 weeks. Analysis of the day 14 MADRS scores on an intent-to-treat basis revealed a treatment-by-centre interaction, with a significant effect of pindolol being demonstrable at only one centre. At this centre, 25% of the paroxetine plus pindolol group and 0% of the paroxetine plus placebo group showed a decrease of at least 50% from baseline MADRS by day 4 (p < 0.05). At day 14, the proportions were 73% and 7%, respectively (p < 0.001). Analysis of covariance on a "perprotocol" population demonstrated a significant accelerator effect of pindolol at days 4 and 7 in the absence of a treatment-by-centre interaction, but a centre effect was apparent at later time-points. The results suggest that the latency of antidepressant action can be reduced with pindolol augmentation. A large multicentre study is in progress to investigate this effect further.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / adverse effects
  • Adult
  • Aged
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / administration & dosage*
  • Paroxetine / adverse effects
  • Pindolol / administration & dosage*
  • Pindolol / adverse effects
  • Psychiatric Status Rating Scales
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Serotonin Uptake Inhibitors / adverse effects


  • Adrenergic beta-Antagonists
  • Serotonin Uptake Inhibitors
  • Paroxetine
  • Pindolol