Efficacy and Harms of Pharmacological Interventions for Anxiety after Traumatic Brain Injury: Systematic Review

J Neurotrauma. 2021 Mar;38(5):519-528. doi: 10.1089/neu.2020.7277. Epub 2020 Nov 23.


After a traumatic brain injury (TBI), many persons experience significant and debilitating problems with anxiety. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for anxiety after TBI. We reviewed studies published in English before July 2020 and included original research on pharmacological interventions for anxiety after TBI in adults ≥16 years of age. MEDLINE, PubMed, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched, with additional searching of key journals, clinical trials registries, and international drug regulators. The primary outcomes of interest were reduction in symptoms of anxiety and occurrence of harms. The secondary outcomes of interest were changes in depression, cognition, quality of life, and participation. Data were summarized in a narrative synthesis, and evidence quality was assessed using the Cochrane Risk of Bias tool. Only a single non-peer-reviewed, randomized controlled trial of 19 male military service members with mild TBI met inclusion criteria. This study found no significant effect of citalopram on anxiety symptoms over a 12-week intervention. The trial was stopped early because of poor recruitment, and much of the study detail was not included in the report. The methodological quality of the study was difficult to assess because of the lack of detail. No recommendations could be drawn from this review. There is a critical need for adequately powered and controlled studies of pharmacological interventions for anxiety after TBI across all severities that examine side-effect profiles and consider issues of comorbidity and effects of long-term pharmacotherapy.

Keywords: anxiety; pharmacotherapy; review; traumatic brain injury.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / therapeutic use*
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Anxiety / psychology
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / psychology
  • Humans
  • Quality of Life / psychology
  • Randomized Controlled Trials as Topic / methods
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Serotonin Uptake Inhibitors