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
Howland RH. Biochemical Effects of Antidepressant Augmentation. Arch Gen Psychiatry. 1995;52(2):156. doi:10.1001/archpsyc.1995.03950140074012
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