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This clinical policy from the American College of Emergency Physicians addresses key issues for the diagnosis and management of adult psychiatric patients in the emergency department. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions: (1) In the alert adult patient presenting to the emergency department with acute psychiatric symptoms, should routine laboratory tests be used to identify contributory medical conditions (nonpsychiatric disorders)? (2) In the adult patient with new-onset psychosis without focal neurologic deficit, should brain imaging be obtained acutely? (3) In the adult patient presenting to the emergency department with suicidal ideation, can risk-assessment tools in the emergency department identify those who are safe for discharge? (4) In the adult patient presenting to the emergency department with acute agitation, can ketamine be used safely and effectively? Evidence was graded and recommendations were made based on the strength of the available data.