A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors

Background: Pindolol has been reported to hasten the antidepressant action of selective serotonin reuptake inhibitors in open-label and placebo-contro lled trials. Pilot studies also suggested that pindolol could augment the a ntidepressant response in unresponsive patients. We investigated whether th e addition of pindolol can induce a rapid response in treatment-resistant p atients. Methods: After a single-blind lead-in placebo phase of 5 days to exclude pl acebo responders, 80 outpatients with major depression who did not respond to a minimum of 6 weeks of treatment with clomipramine hydrochloride, 150 m g/d; fluoxetine hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or p aroxetine hydrochloride, 40 mg/d, were randomly assigned to additionally re ceive placebo (3 times daily) or pindolol (2.5 mg 3 times daily) for 10 day s. The median number of ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating Scale for Depression and Montgomery-Asberg S cale 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 patien ts 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 concentrat ion 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, i t does not elicit a rapid clinical response in treatment-resistant patients within a 10-day period.