Antidepressant treatment history as a predictor of response to scopolamine: clinical implications.
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 naïve 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 (4ug/kg) sessions 3 to 5 days apart). The Montgomery-Asberg 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 naïve 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 naïve subjects had lower MADRS scores than treatment resistant patients; this was significant after the second scopolamine infusion (t=2.15, p=0.03).


CONCLUSIONS
Post-hoc analysis: Also, we used a single regimen to administer scopolamine, and smokers were excluded from the sample, limiting generalizability.


CONCLUSIONS
Treatment naïve and treatment resistant patients showed improved clinical symptoms following scopolamine, while those who were treatment naïve showed greater improvement. Scopolamine rapidly reduces symptoms in both treatment history groups, and demonstrates sustained improvement even in treatment resistant patients.
National Institutes of Health/National Institute of Mental Health,Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5561, Bethesda, MD 20814-9692, USA. Electronic address: brockmeyerjs@mail.nih.gov.
Jessica S
JS
Ellis
National Institutes of Health/National Institute of Mental Health,Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5561, Bethesda, MD 20814-9692, USA; National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Bethesda, MD, 20814-9692, USA.
Carlos A
CA
Zarate
National Institutes of Health/National Institute of Mental Health,Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5561, Bethesda, MD 20814-9692, USA; National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Bethesda, MD, 20814-9692, USA.
David A
DA
Luckenbaugh
National Institutes of Health/National Institute of Mental Health,Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5561, Bethesda, MD 20814-9692, USA; National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Bethesda, MD, 20814-9692, USA.
Maura L
ML
Furey
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012601:Scopolamine / Q000627:therapeutic use*; D055815:Young Adult
D000928:Antidepressive Agents; D012601:Scopolamine
Antidepressant; Depression; Scopolamine; Treatment history; Treatment resistant