Ketamine for Depression and Suicide Risk

This was a single-arm, open-label trial conducted in two phases. During the acute-phase, i.v.
ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive
symptom remission (Montgomery Åsberg Depression Rating Scale (MÅDRS)) total score less than
or equal to 9 measured 24h after any acute-phase infusion) received continuation-phase
treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks.
Remission could occur after any of the 6 acute-phase infusions, at which point the next
infusion was the first (of four) continuation-phase infusions. Individuals who remitted
during acute-phase and completed continuation-phase treatment had 4 additional weekly
post-continuation follow-up visits.Those who responded to i.v. ketamine (less than or equal
to 50% reduction from baseline in MÅDRS total score) but did not remit during acute-phase
were not eligible for continuation-phase treatment. Suicidal ideation was assessed clinically
throughout the trial, supplemented by scores on the MÅDRS suicide item.

Inclusion Criteria:

- Current psychiatric hospital inpatient at Mayo Clinic at time of initiation of
treatment.

- Ability to provide informed consent

- Male/Female

- Age 18-65 yrs.

- Major Depressive Disorder or Bipolar Disorder I or Bipolar Disorder II with Patient
Health Questionnaire-9 (PHQ 9) score ≥15 at hospital assessment

- Treatment resistant depression (TRD) as defined by at least two previous
antidepressant or mood stabilizing treatments for depression in adequate dose for 8
weeks

- Patient reported overall suicide risk score ≥3 on the Suicide Status Form (SSF II-R)
or score of ≥1on Item 9 of PHQ-9 (all at admission assessment)

- Ability to pass comprehension assessment test related to effects of ketamine and trial
objectives and criteria

- Voluntary admission

Exclusion Criteria:

- Diagnosis of schizophrenia, schizoaffective disorder, or active psychosis

- Index episode of depression greater than 2 years

- Ongoing prescription of ≥4 mg lorazepam equivalents total daily or a.m. dosing of any
benzodiazepine at time of assessment

- Currently undergoing electroconvulsive therapy, deep brain stimulation or transcranial
magnetic stimulation as acute series or for maintenance

- Any active or unstable medical condition as judged by principal investigator

- Previous use or abuse of methamphetamine, cocaine, stimulants (prescribed and illicit)
within past 12 months

- Any current abuse or dependence of alcohol or drugs (except nicotine) and abuse or
dependence of drugs and alcohol only in full remission (> 1 month, < 12 months).
Patients will be allowed to enroll if their drug and alcohol abuse / dependence is in
full (complete, not partial) sustained (> 1 year) remission.

- History of traumatic brain injury

- Developmental delay and intellectual disorder

- Encephalopathy (clinical diagnosis within prior 12 months of delirium)

- Cognitive disorder (mild and major)

- Previous participation in earlier Ketamine trial

- Pregnancy

- Prisoners

- Involuntarily hospitalized