Effect of pindolol and milnacipran versus milnacipran and placebo on plasma prolactin and adrenocorticotrophic hormone in depressed subjects

Abstract

Evidence that pindolol accelerates the action of antidepressants has been contradictory, and it is not clear why. The present study analyses the relationship between plasma prolactin (PRL) and ACTH levels and changes in relation to a milnacipran and pindolol combination versus milnacipran plus placebo. Eighty depressed patients agreed to take part in a double-blind randomized trial of milnacipran plus pindolol or placebo. Fifty-eight of them agreed to also take measures of ACTH and PRL levels. ACTH and PRL plasma levels were estimated on days 0 and 42 of the 6-week study. Age, gender and time of blood collection were recorded for each individual. The Montgomery-Asberg depression rating scale (MADRS) was used to measure the response to treatment. The patients were grouped into those with higher versus lower basal ACTH levels using the median of the sample (25 ng/l). There were statistical differences in MADRS scores between the treatment groups on day 42. There were correlations between PRL levels on days 0 and 42; age and PRL levels on day 0; time of the PRL sample and the PRL levels on day 0 and day 42; ACTH and PRL levels on day 42. Regression analysis of the 58 patients showed that on day 0, PRL levels were dependent on the ACTH plasma levels on day 0, the time of the collection of the blood sample and the age. On day 42, the PRL levels were dependent on the ACTH levels and the time of the blood collection but not on the age. Patients with lower baseline ACTH levels on day 0 displayed a better clinical outcome when taking the combination of milnacipran and pindolol as shown in the differences in MADRS on day 42. The same group of patients showed lower PRL levels on day 42. ACTH plasma levels at baseline or screening may help to predict the response to antidepressant treatment.