Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

Inclusion Criteria

• •1. Veterans and non-Veterans between the ages of 21-65.
• •2. Diagnosis of Major Depressive Episode (unipolar or bipolar) as determined by the Mini International Neuropsychiatric Interview (MINI).
• •3. Antidepressant-resistant depressive symptoms, defined by a history of failure of one or more adequate antidepressant trials.
• •4. Stable doses of antidepressants (if prescribed) for a period of four weeks or longer at the time of randomization, except for MAOIs which are prohibited.
• •5. Stable course of psychotherapy (if engaged in) for a period of four weeks or longer at the time of randomization.
• •6. Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile. For those women who are taking an oral contraceptive, we will also ask that they use (or ask their partners to use) a barrier method contraceptive.
• •7. Able to provide written informed consent according to VA HSS guidelines.
• •8. Ability to read and write in English.
• •9. A score greater than or equal to 18 on the Montgomery Åsberg Depression Rating Scale (MADRS).