Ketamine and Scopolamine Infusions for Treatment-resistant Major Depressive Disorder

Combination of Anticholinergic and Glutamatergic Effects in Treatment-resistant Major Depressive Disorder. A Pilot Study

Ketamine infusions resulted in an acute reduction in global depression scores and in severity of suicidal ideation. Scopolamine infusions produced also a significant improvement in depression that was sustained over time. We therefore plan to investigate the feasibility and efficacy of open-label repeated intravenous administration of ketamine and scopolamine combined in this population of severely depressed, treatment-resistant patients. The results from this study could lead to the development of new strategies for the treatment of patients with TRD.

Patients will undergo two weeks of prospective observation, they will then receive IV infusions of ketamine, scopolamine or both per randomization as augmentation of their ongoing antidepressant regime. The schedule of administration will be twice a week of three weeks. After this phase the subject will be followed with assessments every two weeks for three months.

Subjects assigned to this paradigm will receive a 15 minute infusion of normal saline (placebo) followed by IV ketamine at 0.25mg/kg over 45 minutes twice a week for 3 weeks.

Subjects will receive a 15 minute infusion of IV scopolamine 2ug/kg followed by a 45 minute infusion of normal saline (placebo).

Subject will receive an IV scopolamine infusion at a dose of 2ug/kg over 15 minutes, followed by an IV infusion of ketamine at a dose of 0.25mg/kg over 45 minutes.

ketamine IV 0.25mg/kg infusions twice a week for 3 weeks as augmentation of ongoing antidepressant regimen.

Scopolamine 2ug/kg over 15 minutes twice a week for 3 weeks as augmentation of ongoing antidepressant regimen

Subjects will be monitored for emergence of side effects weekly for the first 8 weeks, then every two weeks for 8 weeks.

Inclusion Criteria: Outpatients with sever treatment-resistant depression Currently depressed Currently under regular psychiatric care On an aggressive antidepressant regimen, stable for 4 weeks Exclusion Criteria: No history of other major psychiatric illnesses, including bipolar disorder No history of psychosis No history of drug abuse No major medical illness or unstable medical condition.