Pindolol augmentation of antidepressants: a review and rationale

To critically review the literature on clinical trials in which pindolol, a 5HT1A receptor antagonist, has been used to augment the effects of antidepressants in patients with depression and to examine the pharmacodynamics and pharmacokinetics that may underlie such augmentations.

The available literature from the previous 10 years relating to the clinical use of pindolol in combination with antidepressants was critically examined. This was placed in the context of its pharmacodynamic rationale, and evidence supporting its use was critically reviewed.

A number of open-label and placebo-controlled, double-blind trials on patients with depression showed conflicting results as to the value of adding pindolol to various antidepressant regimens in reducing latency or in augmenting the antidepressant effect in treatment-resistant cases. While pre-clinical studies using electrophysiological and microdialysis techniques suggest utility in terms of increases in extracellular concentration of 5-hydroxy-tryptamine (5HT) in serotonergic projection areas, few studies have examined the possibility of drug-drug interactions and subsequent elevated plasma levels of antidepressant.

Pre-clinical studies suggest possible advantages of pindolol augmentation of antidepressant regimens and the achievement of faster acting antidepressants. The results of investigations in patients with depression have so far been conflicting. There exists the possibility of drug-drug interaction in pindolol/antidepressant augmentation strategies which remains to be examined.