Ketamine in the Treatment of Suicidal Depression

Patients currently taking psychiatric medications may continue them during the study.
However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they
will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but
none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be
permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of
benzodiazepine may need to be reduced so that they can do without it during the 24 hours
pre-infusion.

Depressed participants are randomly assigned to receive a single dose of Ketamine(0.5 mg/kg)
or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study
is "double-blind," meaning patients and study staff will not know which medication is in the
infusion.

If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he
will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). S/he
will then start treatment with a standard antidepressant, unless s/he is not already taking
one.

After the infusion(s), participants will have weekly research interviews for 6 weeks to
monitor response.

If a patient does have a sufficient infusion response, and s/he is not already taking an
antidepressant, then s/he will receive 6-weeks antidepressant research treatment with
Sertraline, Fluoxetine, Paroxetine, or Escitalopram, followed by open clinical treatment.
However, if s/he is already taking an antidepressant, then s/he will receive open treatment.
If s/he does not have a sufficient infusion response, then s/he will receive open treatment.

Participation in this study requires a brief inpatient stay, at no cost, at the New York
State Psychiatric Institute (NYSPI).

Eligible participants enrolled in this study will be offered medication management visits at
no cost for a total of up to 6 months from the date of enrollment combining inpatient and
outpatient treatment. Study medications (Sertraline, Fluoxetine, Paroxetine, Escitalopram,
Lorazepam, Zolpidem) will be at no cost during the 6 months. The study will not provide other
medications at no cost.

INCLUSION CRITERIA:

- Unipolar depression with current major depressive episode (MDE). Participants may be
psychiatric medication-free, or if on psychiatric medication, not responding
adequately given current MDE with suicidal ideation (See 2).

- Moderate to severe suicidal ideation

- 18-65 years old

- Participants must agree to a voluntary admission to an inpatient research unit at the
New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or
longer if clinically necessary.

- Pre-menopausal female participants of child-bearing potential must be willing to use
an acceptable form of birth control during study participation such as condoms,
diaphragm, or oral contraceptive pills.

- Able to provide informed consent

- Participants 61-65 years old must score a 25 or higher on the Mini-Mental State
Examination (MMSE) at screening.

EXCLUSION CRITERIA:

- Unstable medical condition or neurological illness, including baseline hypertension
(BP>140/90) or significant history of cardiovascular illness.

- Significant ECG abnormality

- Pregnant or lactating

- Diagnosis of bipolar disorder or psychotic disorder

- Contraindication to any study treatment.

- Inadequate understanding of English.

- Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.

- Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3
days pre-infusion.

- A diagnosis of sleep apnea.