Dopaminergic sensitivity and prediction of antidepressant response

Abstract

This study was designed to examine neuroendocrine predictors of antidepressant response to the selective serotonin reuptake inhibitor (SSRI) paroxetine. We assessed the prognostic utility of the apomorphine stimulation test by examining the relationship between pretreatment change in growth hormone (GH) following apomorphine and acute response to paroxetine treatment. We hypothesized that those subjects with most marked pretreatment dopaminergic supersensitivity, as manifested by greatest change in GH, would be most likely to show an early antidepressant response and would also be more likely to develop manic or hypomanic symptoms on paroxetine. Contrary to our hypothesis, greater dopamine postsynaptic sensitivity was associated with greater resistance to paroxetine treatment. In our sample of 13 subjects with a major depressive episode, pretreatment GH response to apomorphine per unit weight was inversely correlated with change in Hamilton depression rating scale following 6 weeks of paroxetine. Within the group of subjects who showed mood elevation on paroxetine, there was a trend towards greater GH response being associated with slower antidepressant response. With regard to the development of manic or hypomanic symptoms on paroxetine, change in GH per unit weight not did distinguish the two subjects who subsequently developed paroxetine-induced hypomania from other subjects. The seven subjects with previous antidepressant-induced hypomania did not differ from the other subjects in change in GH response per unit weight. The finding that subjects who had low dopamine receptor responsivity pretreatment were more likely to have an antidepressant response with paroxetine is consistent with recent suggestions that the therapeutic effect of SSRIs may be mediated through increased dopamine receptor sensitivity in the mesolimbic system. Further work assessing pretreatment and post-treatment GH response to apomorphine will help to test the hypothesis that low dopamine receptor responsivity predicts antidepressant response to SSRIs.