Dopaminergic sensitivity and prediction of antidepressant response

This study was designed to examine neuroendocrine predictors of antidepress ant response to the selective serotonin reuptake inhibitor (SSRI) paroxetin e. We assessed the prognostic utility of the apomorphine stimulation test b y examining the relationship between pretreatment change in growth hormone (GI-I) following apomorphine and acute response to paroxetine treatment. We hypothesized that those subjects with most marked pretreatment dopaminergi c supersensitivity, as manifested by greatest change in GH, would be most l ikely to show an early antidepressant response and would also be more likel y to develop manic or hypomanic symptoms on paroxetine. Contrary to our hyp othesis, greater dopamine postsynaptic sensitivity was associated with grea ter 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 sho wed mood elevation on paroxetine, there was a trend towards greater GH resp onse being associated with slower antidepressant response. With regard to t he development of manic or hypomanic symptoms on paroxetine, change in GH p er unit weight not did distinguish the two subjects who subsequently develo ped paroxetine-induced hypomania from other subjects. The seven subjects wi th previous antidepressant-induced hypomania did not differ from the other subjects in change in GH response per unit weight. The finding that subject s who had low dopamine receptor responsivity pretreatment were more likely to have an antidepressant response with paroxetine is consistent with recen t suggestions that the therapeutic effect of SSRIs may be mediated through increased dopamine receptor sensitivity in the mesolimbic system. Further w ork assessing pretreatment and post-treatment GN response to apomorphine wi ll help to test the hypothesis that low dopamine receptor responsivity pred icts antidepressant response to SSRIs.