• John M Kelly, Gordon D Rubenfeld, Neil Masson, and Arimie Min.
• 1Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 2Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada. 3Department of Psychiatry, Stobhill Hospital, Glasgow, United Kingdom. 4University of Glasgow, Glasgow, United Kingdom. 5Royal College of Surgeons in Ireland, Dublin, Ireland. 6Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
• Crit. Care Med. 2017 Jun 1; 45 (6): e607-e616.

ObjectiveSelective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors are among the most commonly prescribed drugs in patients admitted to the ICU. Our objective was to systematically review available literature for evidence of benefit or harm in ICU patients resulting from chronic effects, continued use, or withdrawal.Data SourcesMedline, Embase, and Cochrane Central Register of Controlled Trials (1990 to November 2014).Study SelectionWe searched for studies of ICU patients with recorded selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor prescription before or during admission, and reporting morbidity, mortality, adverse events, and resource measures like ICU length of stay. We considered all study designs. We excluded studies of deliberate overdose and depression in non-ICU settings. Two authors independently and in duplicate screened citations and reviewed text of studies to apply selection criteria.Data ExtractionTwo authors abstracted data on patient characteristics in exposed and control groups; use of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors previously or during ICU; comparator intervention; and outcomes, and also assessed methodologic quality.Data SynthesisThe database search retrieved 4,172 unique citations, of which 289 were reviewed, and 13 studies representing a total of 20,048 patients met selection criteria. There were five cohort studies, one case series, and seven case reports. Only one case report suggested benefit from selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor use and 11 studies reported morbidity in patients using these medications at admission to ICU. However, due to inadequate drug administration reporting, it was generally unclear if outpatient selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors were continued in ICU, complicating interpretation.ConclusionsThere may be excess morbidity in critically ill selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor users, but uncertainty remains whether this is due to chronic effects, ongoing use, or drug withdrawal. Further research with improved standards of drug administration reporting is needed to help clinicians decide when to use selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors in critically ill patients.

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