HOW LONG SHOULD PINDOLOL BE ASSOCIATED WITH PAROXETINE TO IMPROVE THEANTIDEPRESSANT RESPONSE

A double-blind study was undertaken to investigate the period of treat ment with the beta-adrenoreceptor/5-hydroxytryptamine 1A (5-HT1A) anta gonist pindolol required to enhance the antidepressant effects of paro xetine. After 1 meek of a placebo run-in period, 63 untreated major de pressive inpatients mere randomly assigned to three different groups. Group 1 received paroxetine (20 mg/day) plus placebo (4 weeks). Group 2 received paroxetine (20 mg/day) plus pindolol (7.5 mg/day) for 1 mee k and placebo for 3 weeks. Group 3 received both active treatments for the entire duration of the study (4 weeks). Clinical response was def ined as a reduction of the score in the Hamilton Rating Scale for Depr ession (HAM-D) to 8 or below. Also, to preliminarily examine whether b eta-adrenoreceptor blockade was involved in the action of pindolol, an other group of 10 inpatients was treated in an open-label manner with paroxetine (20 mg/day) plus 50 mg/day of the beta-adrenergic antagonis t metoprolol, devoid of significant affinity for 5-HT1A receptors. At- endpoint, the incidence of treatment-emergent side effects did not sig nificantly differ among the three groups. After 1 and 2 weeks of treat ment, the two groups treated with paroxetine plus pindolol displayed a significantly greater response rate than the group treated with parox etine plus placebo. At study completion, only the patients treated wit h pindolol for the entire period showed a significantly greater respon se rate (p = 0.05). HAM-D scores mere also significantly lower at endp oint in patients treated with the combination for 4 weeks (p = 0.00003 ). The group of patients treated with paroxetine and metoprolol exhibi ted a side-effect profile comparable to that of paroxetine alone. Resp onse rates mere also comparable. These findings support the efficacy o f pindolol, but not of metoprolol, in accelerating the antidepressant effect of paroxetine and suggest that the administration of pindolol f or the entire period of the acute treatment may increase the efficacy of paroxetine.