Electroconvulsive therapy (ECT) is a highly effective treatment for severe major depression. It has been estimated that approximately 10 percent of all patients admitted to the hospital for treatment of major depressive disorder receive ECT.~However, not all patients who receive ECT respond, and of those who do, not all achieve remission. Furthermore, while there is a wide range in the number of ECT treatments done among all people with depression, the average is approximately eight treatments. Because treatments are usually done three times per week (Monday, Wednesday, and Friday), the minimal length of stay for the average person receiving inpatient ECT is typically greater than two weeks.~Finally, ECT is not without risk, and every round of ECT incurs additional risk of not just the treatment itself, but also the risks of general anesthesia. Thus, although ECT is a robust mode of treatment for Major Depressive Disorder (MDD), there remains a need for improved treatment efficacy and speed of onset. Improving the efficacy of ECT would not only benefit individuals with MDD, but also have far-reaching effects for the health care system as it could impact the cost and resources utilized.~Ideally, an agent could be added to augment the effect of ECT, both in terms of efficacy as well as speed of onset. In 2006, Furrey et al, reported the rapid antidepressant effect of the antimuscarinic drug, scopolamine, delivered parenterally. Significant antidepressant effect was found after the first scopolamine administration. The improvement was reported immediately following the first IV administration, increased across all treatments, and was sustained into the placebo crossover period.~Scopolamine is an anticholinergic muscarinic agent, with activity in the CNS and pilot data to suggest a significant impact on rapidly improving depressive symptoms in patient with MDD, when administered IV. Thus, it serves as a reasonable choice to augment the effects of ECT in the treatment of patients with MDD.~Primary Aim 1) Assess the ability of scopolamine to augment the antidepressant effects of ECT.~Hypothesis 1a: Patients receiving ECT plus scopolamine will have significantly greater mean improvement on total HAM-D score between baseline and endpoint than those receiving ECT plus placebo.~Hypothesis 1b: Patients receiving scopolamine in addition to ECT will require fewer mean ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.~Primary Aim 2) Evaluate the hypothesis that scopolamine will shorten the time to response and remission for patients receiving ECT.~Hypothesis 2: Time to response and to remission in the Scopolamine group will be significantly shorter compared to ECT alone.~Secondary Aim: Provide evidence for the tolerability of intravenous scopolamine administered during ECT.~Hypothesis 3a: There will be no between group difference (between ECT plus scopolamine vs ECT plus placebo) in mean number of ECT sessions withheld due to cognitive impairment (as determined by attending psychiatrist).~Hypothesis 3b: There will be no between group differences (between ECT plus scopolamine vs ECT plus placebo) with regards to the mean number of moderate to severe side effects.~Hypothesis 3c: There will be no significant difference between the scopolamine plus ECT group and the placebo plus ECT group on mean levels of physiological measures of ECT including: heart rate, blood pressure, seizure length, duration of muscle paralysis, duration of asystole, and energy need to induce seizure.~Exploratory Analyses: we will assess whether the scopolamine plus ECT group will have a shorter average length of stay on the inpatient psychiatric unit compared to those receiving ECT plus placebo.~We will also assess whether the scopolamine plus ECT group will have significant differences in the cognitive measures at endpoint compared to those receiving ECT plus placebo.
The primary purpose of this study is to assess the ability of scopolamine to improve the antidepressant effects of ECT and to determine whether scopolamine will shorten the time to response and remission for patients receiving ECT.~The hypothesis are:~Patients receiving ECT plus scopolamine will have greater improvement in depression symptoms than those receiving ECT plus placebo.~Patients receiving scopolamine in addition to ECT will require fewer ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.~Time to response and to remission in the scopolamine group will be significantly shorter compared to ECT alone.