Baseline mood-state measures as predictors of antidepressant response to scopolamine

Abstract

Identifying predictors of antidepressant response will facilitate the successful treatment of patients suffering from depression. Scopolamine produces robust antidepressant responses in unipolar and bipolar depression. Here we evaluate the potential for baseline self-ratings to predict treatment response to scopolamine. Fifty-one unipolar and bipolar patients participated in a double-blind, placebo-controlled crossover trial. Following a single-blind placebo session, participants randomly received P/S or S/P (P=3 placebo; S=3 scopolamine (4μg/kg) sessions). Mood-state self-ratings (Profile of Mood State (POMS) and Visual Analog Scales (VAS)) and depression severity (Montgomery-Åsberg Depression Rating Scale (MADRS)) were obtained before each infusion. Day 1 (baseline/placebo) self-ratings were used in a discriminant function analysis to identify linear combinations of individual items that predict response. The discriminant analysis significantly separated responders from non-responders in both the unipolar and bipolar diagnostic subgroups. The discriminant functions accurately classified over 85% of patients as responders/non-responders. The POMS depression subscale significantly correlated with clinical response, as did the VAS restlessness, sad, and irritated scales. These results indicate that self-report mood-ratings obtained before treatment can predict response outcome to scopolamine, and suggest that a constellation of mood-state features may be related to clinical response.

Conflict of interest statement

Disclosure/Conflict of Interest

The NIMH has filed a use-patent for the use of scopolamine in the treatment of depression, and Dr.’s Furey and Drevets are identified as co-inventors on this pending patent application in the US and an existing patent in Europe.

Published by Elsevier Ireland Ltd.

Figures

Figure 1

Scatterplot of individual subjects discriminant function scores are shown for responders and non-responders with major depressive disorder (panel A) and with bipolar disorder (panel B) separately. The bars indicate the group means. In major depressive disorder, the stepwise analysis identified seven mood-rating variables that best discriminated responders from non-responders, including depression, anger, fatigue and vigor from the POMS, and altertness, drowsy, and happy from the VAS. The discriminant function significantly separates responders from non-responders (X2= 22.6, p= 0.002) and the mean function scores differs between the two groups (t= 6.1, p<0.001). In bipolar disorder, the stepwise analysis identified seven mood-rating variables that best discriminated responders from non-responders, including depression and anger from the POMS, and the restlessness and irritated scales from the VAS. The discriminant function significantly separates responders from non-responders (X2= 11.2, p= 0.025) and the mean function scores differs between the two groups (t= 5.0, p<0.001).

Figure 2

Scatterplots reflect correlations between the magnitude of antidepressant response (percent improvement in MADRS score from baseline to study end) and baseline self-report mood ratings in a patient group that includes major depressive and bipolar disorder patients. The magnitude of antidepressant response correlated significantly with the depression subscale of the POMS (panel A), as well as the restlessness (panel B), sadness (panel C) and irritated (panel D) scales of the VAS. The correlation value and associated probability value are presented for each graph. The absence of a correlation between the magnitude of the antidepressant response and baseline depression severity is reflected in the panel insert (panel E).