Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Condition: Depression
MeSH terms: Depression
Intervention: Ketamine; sirolimus; Placebo
Intervention description: . Subjects will receive an infusion of ketamine (0.5 mg/kg infusion over approximately 40 minutes). All subjects will receive two ketamine infusions-once with a placebo and once with a single dose of sirolimus (6 mg, oral administration).; Subjects will receive a single 6 mg oral dose via oral solution of sirolimus or a dose of placebo approximately two hours prior to the infusions. As above, the order of placebo and sirolimus is randomized. The sirolimus dose as well as the placebo solution will be given in 6 ounces of orange juice.; Placebo oral dose
Intervention MeSH terms: Sirolimus; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The aim of the study is to provide insight into the impact of the immunosuppressant drug
      sirolimus, on the antidepressant effects of the prototypal rapid-acting antidepressant
      medication, ketamine.
    

Eligibility criteria:

        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).

        Exclusion Criteria:

          1. Subjects with a diagnostic history of schizophrenia or schizoaffective disorder, or
             currently exhibiting manic or mixed episodes or psychotic features as confirmed by the
             Mini International Neuropsychiatric Inventory.

          2. Current, ongoing serious suicidal risk as assessed by evaluating investigator or by
             scoring 5 or more on the item-10 of the MADRS.

          3. Patients with unstable or inadequately controlled medical conditions.

          4. Patient requiring prohibited medication.

          5. Patient with history of organ transplant.

          6. Meet criteria for a diagnosis of substance dependence (amphetamines, cocaine,
             hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within the three
             months prior to screening date.

          7. Positive urine drug screen for cannabis, cocaine, PCP, or barbiturates.

          8. Positive pregnancy test at screening at any screen given during the study.

          9. Known sensitivity to sirolimus or ketamine.

         10. History of sensitivity to heparin or heparin-induced thrombocytopenia.

         11. Resting blood pressure lower than 85/55 or higher than 150/95, or resting heart rate
             lower than 45/min or higher than 100/min.