How does pindolol improve antidepressant action?

Since 1994, the beta -adrenoceptor and 5-HT1A/1B receptor ligand pindolol h as been used to accelerate or enhance the clinical effects of antidepressan t drugs, such as the selective 5-HT reuptake inhibitors (SSRIs), that act p rimarily on 5-HT-containing neurones. Pindolol was initially thought to act by preventing the inhibition of 5-HT release, elicited by SSRIs and other 5-HT-acting drugs, as a result of its ability to antagonize the action of 5 -HT at midbrain raphe 5-HT1A autoreceptors that control the activity of asc ending 5-HT-mediated pathways. However, the partial agonist properties of p indolol at 5-HT1A receptors and beta -adrenoceptors suggest that other expl anations for its action are also possible. In this article, recent controve rsial data on the mechanism of action of pindolol, which are crucial for th e development of more rapid and efficient antidepressant therapies, will be discussed.