Effect of Pindolol on Onset of Action of Paroxetine in the Treatment of Major Depression: Intermediate Analysis of a Double-Blind, Placebo-Controlled Trial

Abstract

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.

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

“…This rapid restoration of the sensitivity to electrical stimulation (i.e., relative increase in reward) may be attributable to increased serotonin function in forebrain structures, such as the frontal cortex, the hippocampus and the striatum (e.g., Bel and Artigas 1993;Dreshfield et al 1996Dreshfield et al , 1997Invernizzi et al 1994;Gobert and Millan 1999;Rutter et al 1994). The present data are consistent with the hypothesis that the rapid onset of clinical antidepressant action of SSRIs when combined with pindolol (Bordet et al 1998;Tome et al 1997aTome et al , 1997bZanardi et al 1997Zanardi et al , 1998; however, see Berman et al 1997Berman et al , 1999) is partly attributable to pindolol's 5-HT 1A antagonist properties. Nevertheless, other receptors, such as the 5-HT 1B and ␣-adrenergic receptors, for which pindolol has antagonist and/or partial agonist properties, and other neuromechanisms may also contribute to pindolol's augmentation of SSRI antidepressant effects.…”

“…Thus, such a drug combination may have rapid therapeutic effects that may be detectable during the short-lasting drug withdrawal. Second, the combination of a SSRI with pindolol [antagonist at 5-HT 1A , 5-HT 1B , and ␤ -adrenergic receptors (Assie and Koek 1996;Bourin et al 1998;Gobert and Millan 1999;Hoyer and Schoeffter 1991;Newman-Tancredi et al 1998); also reported to act as a partial agonist at 5-HT 1A and ␣ -adrenergic receptors (Clifford et al 1998;Fornal et al 1999aFornal et al , 1999bFornal et al , 1999cGobert and Millan 1999; Palmier 1994a, 1994b)] accelerates the onset of antidepressant action of SSRIs in humans (Bordet et al 1998;Zanardi et al 1997Zanardi et al , 1998, or augments the antidepressant response to SSRIs in terms of both magnitude and duration of the response (Maes et al 1999;Perez et al 1997;Tome and Isaac 1998; for review, see McAskill et al 1998; however, see Berman et al 1997 however, see Berman et al , 1999Tome et al 1997aTome et al , 1997b. In the present study, instead of pindolol, which has multiple receptor actions, the relatively selective 5-HT 1A receptor antagonist p-MPPI was used.…”

Potentiation by (-)Pindolol of the Activation of Postsynaptic 5-HT1A Receptors Induced by Venlafaxine

“…As a direct outcome of this research endeavour, it has been reported, in six of the seven double blind clinical studies assessing this issue to date, that the addition of pindolol to selected antidepressant agents is a successful strategy to shorten the delay of therapeutic action in major depression (Maes et al 1996;Berman et al 1997;Tome et al 1997;Pérez et al 1997;Zanardi et al 1997Zanardi et al , 1998Bordet et al 1998).…”

Differential Occupancy of Somatodendritic and Postsynaptic 5HT1A Receptors by Pindolol A Dose-Occupancy Study with [11C]WAY 100635 and Positron Emission Tomography in Humans

“…Initial open label clinical studies reported that the co-administration of pindolol with SSRI enhanced and/or accelerated the antidepressant effects of the SSRIs (Artigas et al 1994;Blier and Bergeron 1995;Bakish et al 1997). However, the results of subsequent double-blind controlled trials have been less consistent (Maes et al 1996(Maes et al , 1999Berman et al 1997Berman et al , 1999Perez et al 1997Perez et al , 1999Tome et al 1997;Zanardi et al 1997Zanardi et al , 1998Bordet et al 1998).…”