Pindolol augmentation of antidepressants: a review and rationale

Objective: To critically review the literature on clinical trials in which pindolol, a 5HT(1A) receptor antagonist, has been used to augment the effec ts of antidepressants in patients with depression and to examine the pharma codynamics and pharmacokinetics that may underlie such augmentations. Method: The available literature from the previous 10 years relating to the clinical use of pindolol in combination with antidepressants was criticall y examined. This was placed in the context of its pharmacodynamic rationale , and evidence supporting its use was critically reviewed. Results: 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 i n augmenting the antidepressant effect in treatment-resistant cases. While pre-clinical studies using electrophysiological and microdialysis technique s suggest utility in terms of increases in extracellular concentration of 5 -hydroxy-tryptamine (5HT) in serotonergic projection areas, few studies hav e examined the possibility of drug-drug interactions and subsequent elevate d plasma levels of antidepressant. Conclusions: Pre-clinical studies suggest possible advantages of pindolol a ugmentation 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 in teraction in pindolol/anti-depressant augmentation strategies which remains to be examined.