Pindolol, 5-Hydroxytryptamine, and Antidepressant Augmentation

I read with interest the letter by Howland¹ in the February issue of the Archives on the use of pindolol to augment antidepressant effects.² Howland argues that pindolol could be acting through β-adrenergic receptors to potentiate the effects of 5-hydroxytryptamine (5-HT) reuptake inhibitors and monoamine oxidase inhibitors. Based on the augmentation of antidepressant effects induced by buspirone hydrochloride,³ a partial 5-HT_1A agonist, he also found it difficult to reconcile the fact that agonists and antagonists of the same receptors may produce the same effect. It is important to clarify this issue because it may be critical to understanding the mode of action of pindolol and other Potentially useful 5-HT_1A antagonists.

The 5-HT_1A receptors are anatomically and pharmacologically heterogeneous. They are localized on the soma and dendrites of serotonergic neurons in the raphe nuclei (presynaptic or somatodendritic location) or on other cell types, in limbic