NCT02295787.

Study name	Intranasal ketamine for late‐life depression and suicidal ideation
Methods	A single subanaesthetic dose (0.5 mg/kg, intravenous) of ketamine (an anti‐glutamatergic compound) rapidly (within 24 hours) and robustly decreases depression and suicidality in treatment‐resistant patients, and this effect is sustained for about one week. Intranasal administration has similar effects, good tolerability, and significantly easier administration. We propose to investigate intranasal ketamine as a novel anti‐suicidal treatment for patients with LLD and suicidal ideation. This study will be a randomised, placebo‐controlled, double‐blind trial; intranasal doses will be administered 50 mg every three days. We will enrol 30 patients with a diagnosis of LLD. All patients must be depressed, must endorse some level of suicidal ideation, and must not have a history of psychosis or substance misuse disorders The proposed study involves three phases: 1) 2‐week medication stabilisation period; 2) double‐blind treatment with intranasal ketamine versus placebo, with visits every three days for six total administrations; 3) prospective follow‐up for 3 months, with visits every two weeks. Clinical assessment scales to be administered at each visit will include the HRSD; primary outcome measure; Columbia‐Suicide Severity Rating Scale (C‐SSRS); Clinical Global Impression (CGI); and side‐effect measures. Self‐rated scales measuring depression, anxiety, level of functioning, and quality of life will also be administered. In accordance with NIMH research guidelines for patients at risk for suicide, and in collaboration with the IRB, a detailed safety plan has been developed for the management of worsening suicidality ‐ and has been implemented for other depression studies in our department. All adverse events will be recorded to determine tolerability. To analyse the efficacy data, we will apply a linear random mixed model for longitudinal data. The change from baseline to post‐baseline times will be the dependent variable, with time as the independent variable; response will be defined as ≥ 50% improvement from baseline on the HRSD. Kaplan‐Meier survival estimates will be used to analyse time‐to‐relapse If intranasal ketamine is found to be safe, effective, and well‐tolerated in patients with LLD and suicidal ideation, it can clinically impact outpatient psychiatric settings. From a research perspective, the discovery of a rapidly‐acting anti‐suicidal agent for treating LLD and suicidal ideation has the potential to: 1) decrease the morbidity and mortality that results from late‐life depression; 2) offer new insights into the neurobiology of depression in older age; and 3) pave the way for the development of other novel therapeutics and treatment targets
Participants	Ages eligible for study: 65 Years and older Genders eligible for study: Both Accepts healthy volunteers: No Inclusion criteria 1) be ≥ 65 years old, 2) provide written informed consent, 3) meet criteria for a primary psychiatric diagnosis of major depressive disorder according to the Structured Clinical Interview for DSM‐IV (SCID) and have a HRSD‐28 total score ≥ 20; depression may have started at any time point in their life, and certain comorbid diagnoses (e.g., anxiety disorders) will be allowed insofar as they are not the primary psychiatric diagnosis, 4) have a history of ≥ 2 failed medication trials during the current episode (per the Massachusetts General Hospital Antidepressant Treatment History Questionnaire; MGH ATRQ), 5) endorse suicidal ideation for more than 2 months, per the Columbia Suicide Severity Rating Scale (C‐SSRS) and have a HRSD‐28 suicide item score ≥ 1 (thoughts that life isn't worth living), 6) be on a stable antidepressant regimen for ≥ 14 days prior to Study Phase II, 7) maintain a treating psychiatrist who is in agreement with study participation, and 8) have a reliable chaperone accompany them home following the completion of the intranasal administration Exclusion criteria •Patients will be excluded if any of the following criteria are met: 1) delirium or dementia diagnosis, 2) unstable medical illness, 3) history of clinically significant cardiovascular disease or electrocardiogram (EKG) findings, or medical conditions that put the patient at risk for possible cardiac side effects, 4) history of multiple adverse drug reactions, 5) current/past history of psychotic disorders or homicidality, 6) active substance use disorders (except nicotine and caffeine) within the past six months, positive urine toxicology screen, or past history of ketamine abuse, 7) requirement of excluded medications (narcotics, barbiturates, theophylline, or St. John's Wort), or 8) concurrent or recent participation in other research studies
Interventions	Ketamine versus placebo
Outcomes	Primary outcome measures: HRSD
Starting date	October 2015
Contact information	Dawn F Ionescu, MD, mailto:dionescu%40partners.org?subject=NCT02295787, 2014D006212, Intranasal Ketamine for Late‐Life Depression and Suicidal Ideation
Notes	NCT02295787