Effect of pindolol on onset of action of paroxetine in the treatment of major depression: intermediate analysis of a double-blind, placebo-controlled trial. Réseau de Recherche et d'Expérimentation Psychopharmacologique.
OBJECTIVE
The purpose of this study was to investigate the effect of pindolol to accelerate the onset of action of paroxetine in patients suffering from major depression.


METHODS
Patients who met DSM-IV criteria for a nonpsychotic disorder, who had no previously treated episode of major depression episode, and who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale were randomly assigned, for the first 21 days, to treatment with paroxetine (20 mg/day) and either pindolol (5 mg t.i.d.) or placebo. Patients were evaluated with the Hamilton depression scale, the Montgomery-Asberg Depression Rating Scale, and Global Clinical Impression (CGI) on days 0 (baseline), 5, 10, 15, 21, 25, 31, 60, 120, and 180.


RESULTS
Intermediate analysis of the first month's results for the first 100 patients (pindolol, N=50; placebo, N=50) was performed. At day 10 there were more improved patients (defined as patients with a maximum score of 10 on the Hamilton depression scale) in the pindolol plus paroxetine group (N=24; 48%) than in the placebo plus paroxetine group (N=13; 26%). At day 5 there was no statistically significant difference, and at day 15 and thereafter, the differences between the two groups disappeared. Hamilton depression scale scores were significantly lower on days 5 and 10 for the pindolol plus paroxetine group (mean=15.7, SD=5.3, and mean=11.7, SD=6.4, respectively) than for the placebo plus paroxetine group (mean=19, SD=5.9, and mean=14.7, SD=6.8); this was also true for Montgomery-Asberg depression scale and CGI scores.


CONCLUSIONS
The addition of pindolol to paroxetine treatment significantly accelerates the onset of therapeutic response in patients suffering from major depression. Nevertheless, the mechanism (pharmacodynamic or pharmacokinetic) of this beneficial effect remains unclear.
Bordet
R
R
Réseau de Recherche et d'Expérimentation Psychopharmacologique (REPP), Centre Hospitalier et Universitaire, Lille, France. bordet@pop.univ-lille2.fr
Thomas
P
P
Dupuis
B
B
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010869:Pindolol / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D017374:Paroxetine; D010869:Pindolol; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors