This study will enroll patients presenting to the emergency department with acute suicidal ideation meeting inclusion and exclusion criteria. Patients will be randomized to one of three arms: ketamine (intervention) or diphenhydramine (control) or placebo (control). Serial measurements will be made in the ED and at follow-up intervals.

Inclusion Criteria:

• Patients age 18 to less than 75 who present to the SAMMC ED with either overt or incidental suicidal ideations with a SADPERSONS score 5 or greater that the treating provider feels warrant formal evaluation.

Exclusion Criteria:

• -Poor vital sign stability hypoxia: O2 < 95%, hypotension: SBP< 90 hypertension: SBP>180 Heart rate: < 50 or >120 Respiratory Rate: <10 or >30
• Altered mental status or intoxication
• Patient is unwilling to participate or provide informed consent
• Any allergy to ketamine or diphenhydramine
• Patient is female of child-bearing age and unwilling to provide urine or blood for HCG analysis
• Pregnancy or breast feeding
• Presence of chronic oxygen-dependent pulmonary disease, liver cirrhosis, or renal disease requiring dialysis
• Presence of ischemic heart disease, heart failure, or a history of unstable dysrhythmias
• Presence of intracranial mass or vascular lesion.
• Presence of a history of psychosis or hallucinations (as assessed by electronic chart review)
• Weight greater than 115 kg or less than 45kg
• History of increased intracranial pressure/hypertensive hydrocephalus
• Non-English speaking patients
• Patient is acutely psychotic
• Provider feels that patient currently or likely will require chemical and/or physical restraints
• History of prolonged QT-interval