A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en Trastorns Afectius

Arch Gen Psychiatry. 1999 Apr;56(4):375-9. doi: 10.1001/archpsyc.56.4.375.


Background: Pindolol has been reported to hasten the antidepressant action of selective serotonin reuptake inhibitors in open-label and placebo-controlled trials. Pilot studies also suggested that pindolol could augment the antidepressant response in unresponsive patients. We investigated whether the addition of pindolol can induce a rapid response in treatment-resistant patients.

Methods: After a single-blind lead-in placebo phase of 5 days to exclude placebo responders, 80 outpatients with major depression who did not respond to a minimum of 6 weeks of treatment with clomipramine hydrochloride, 150 mg/d; fluoxetine hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or paroxetine hydrochloride, 40 mg/d, were randomly assigned to additionally receive placebo (3 times daily) or pindolol (2.5 mg 3 times daily) for 10 days. The median number of ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating Scale for Depression and Montgomery-Asberg Scale for Depression scores were used as primary measures of efficacy.

Results: At end point, the Hamilton and Montgomery-Asberg scores and change from baseline in Hamilton score were not significantly different in patients taking placebo or pindolol. The response rate was equal in both groups (12.5%). No differences in the clinical outcome were found when the various pretreatment subgroups were considered. At end point, the plasma concentration of pindolol was 9.9+/-5.1 ng/mL (mean +/- SD; n = 40).

Conclusions: Although pindolol can accelerate the antidepressant action of selective serotonin reuptake inhibitors in previously untreated patients, it does not elicit a rapid clinical response in treatment-resistant patients within a 10-day period.

Publication types

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

MeSH terms

  • Adult
  • Ambulatory Care
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Evaluation
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / therapeutic use
  • Fluvoxamine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / administration & dosage
  • Paroxetine / pharmacology
  • Paroxetine / therapeutic use
  • Pindolol / administration & dosage
  • Pindolol / pharmacology
  • Pindolol / therapeutic use*
  • Placebos
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / pharmacology
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Single-Blind Method


  • Placebos
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Paroxetine
  • Pindolol
  • Fluvoxamine