[Skip to Navigation]
[Skip to Navigation Landing]
February 1995

Biochemical Effects of Antidepressant Augmentation

Author Affiliations

Western Psychiatric Institute and Clinic 3811 O'Hara St Pittsburgh, PA 15213

Arch Gen Psychiatry. 1995;52(2):156. doi:10.1001/archpsyc.1995.03950140074012

In their report on the use of pindolol to augment selective serotonin (5-HT) reuptake inhibitors and monoamine oxidase inhibitors, Artigas et al1 suggest that this may be mediated by presynaptic 5-HTIA antagonism, resulting in enhanced serotonergic function. Buspirone, a 5-HTIA agonist, also may be effective in augmenting selective 5-HT reuptake inhibitors in refractory depression.2-5 Because pindolol and buspirone have opposite effects on 5-HTIA function, their efficacy is therefore difficult to reconcile on this basis. Furthermore, it is not clear how 5-HTIA antagonism could account for the effect of pindolol, because reduced sensitivity of presynaptic 5-HTIA receptors is found in major depression.6,7

A major metabolite of buspirone is the α2-adrenergicantagonist 1-(2-pyrimidinyl)-piperazine.8,9α2-Adrenergic antagonism by 1-(2-pyrimidinyl)-piperazine could enhance the release of norepinephrine and result in mood elevation,10 which is consistent with the mechanism of antidepressants such as mianserin11