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Ellis JS, Zarate CA, Luckenbaugh DA, Furey ML. 
“Antidepressant treatment history as a predictor of response to scopolamine: clinical implications”. 
Journal of Affective Disorders. 2014 03.
Abstract

BACKGROUND: The intravenous administration of scopolamine produces rapid antidepressant effects. Generally, failing multiple previous antidepressant trials is associated with a poor prognosis for response to future medications. This study evaluated whether treatment history predicts antidepressant response to scopolamine.

METHODS: Treatment resistant patients (2 failed medication trials) (n=31) and treatment na´ve patients (no exposure to psychotropic medication) (n=31) with recurrent major depressive or bipolar disorder participated in a double-blind, placebo-controlled, crossover clinical trial. Following a placebo lead-in, participants randomly received P/S or S/P (P=3 placebo; S=3 scopolamine (4 ug/kg) sessions 3 to 5 days apart). The MontgomeryľAsberg Depression Rating Scale (MADRS) was the primary outcome measure. A linear mixed model was used to examine the interaction between clinical response and treatment history, adjusting for baseline MADRS.

RESULTS: Treatment resistant and treatment na´ve subjects combined responded significantly to scopolamine compared to placebo (F=15.06, p< 0.001). Reduction in depressive symptoms was significant by the first post-scopolamine session (F=42.75, p< 0.001). A treatment history by scopolamine session interaction (F=3.37, p=0.04) indicated treatment na´ve subjects had lower MADRS scores than treatment resistant patients; this was significant after the second scopolamine infusion (t=2.15, p=0.03). Limitations Post-hoc analysis. Also, we used a single regimen to administer scopolamine, and smokers were excluded from the sample, limiting generalizability. Conclusions Treatment na´ve and treatment resistant patients showed improved clinical symptoms following scopolamine, while those who were treatment na´ve showed greater improvement. Scopolamine rapidly reduces symptoms in both treatment history groups, and demonstrates sustained improvement even in treatment resistant patients.
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