Scopolamine produces larger antidepressant and antianxiety effects in women than in men

Abstract

Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 μg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group × block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group × block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block × gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment × block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block × gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

Figure 1

Blocked experimental design reflecting infusion series and assessment sessions for each of the two randomized patient groups. In block I, participants received a series of three infusions of either placebo or scopolamine; in block II, participants again received a series of three infusions and were crossed over to scopolamine or placebo.

Figure 2

Mean MADRS scores (±SE) are shown for each of the seven assessments and the follow-up evaluation are presented for all subjects combined (a), as well as for females (b) and males (c) separately. Mean baseline and study end MADRS scores are also shown (d) separated into female and male subgroups.

Figure 3

Mean baseline and study end HAM-A scores (±SE) are shown separated into female and male subgroups.

Figure 4

Mean CGI-I scores (±SE) are shown for each of the seven assessments and the follow-up evaluation are presented for all subjects combined (a), as well as for females (b) and males (c) separately. Mean baseline and study end CGI-I scores are also shown (d) separated into female and male subgroups.