Effectiveness of Pharmacotherapy for Depression after Adult Traumatic Brain Injury: an Umbrella Review.

Symptoms of depression are common following traumatic brain injury (TBI), impacting survivors' ability to return to work, participate in leisure activities, and placing strain on relationships. Depression symptoms post TBI are often managed with pharmacotherapy, however, there is little research evidence to guide clinical practice. There have been a number of recent systematic reviews examining pharmacotherapy for post TBI depression. The aim of this umbrella review was to synthesize systematic reviews and meta-analyses of the effectiveness of pharmacotherapy for the management of post TBI depression in adults. Eligible reviews examined any pharmacotherapy against any comparators, for the treatment of depression in adults who had sustained TBI. Seven databases were searched, with additional searching of online journals, Research Gate, Google Scholar and the TRIP Medical Database to identify published and unpublished systematic reviews and meta-analyses in English up to May 2020. A systematic review of primary studies available between March 2018 and May 2020 was also conducted. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. The results are presented as a narrative synthesis. Twenty-two systematic reviews were identified, of which ten reviews contained a meta-analysis. No new primary studies were identified in the systematic review. There was insufficient high quality and methodologically rigorous evidence to recommend prescribing any specific drug or drug class for post TBI depression. The findings do show, however, that depression post TBI is responsive to pharmacotherapy in at least some individuals. Recommendations for primary studies, systematic reviews and advice for prescribers is provided. Review Registration PROSPERO (CRD42020184915).

The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).

Effectiveness of pharmacotherapy for depression after traumatic brain injury in adults: an umbrella review protocol.

OBJECTIVE: The objective of this review is to synthesize systematic reviews of the effectiveness of pharmacotherapy vs any other comparator for the management of post-traumatic brain injury depression in adults. INTRODUCTION: Depression following a traumatic brain injury can have a considerable impact on the life of the individual, their family members, and the health care system. There have been several recent systematic reviews and meta-analyses on pharmacologic treatment for depression caused by post-traumatic brain injury. These reviews differ in conduct, quality, and reporting, and have discordant results and conclusions. Therefore, an umbrella review can provide prescribers with a summary of the evidence. INCLUSION CRITERIA: This review will consider systematic reviews of studies of adults 16 years or older who have sustained a traumatic brain injury of any severity at any time in the past, who are receiving pharmacotherapy for depression of any severity in any health care setting. Studies that include the following outcomes will be considered: change in symptoms of depression and occurrence of harms. METHODS: MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Epistemonikos, and PROSPERO will be searched, as well as Google Scholar, ResearchGate, TRIP Medical Database, and hand searching journals. There will be no restriction on publication date. Only systematic reviews published in English will be considered. Screening of articles, assessment of methodological quality, and data extraction will be performed independently by two reviewers. A Grading of Recommendations, Assessment, Development and Evaluation Summary of Findings will be presented. Data will be summarized in narrative form with supporting tables. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020184915.

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

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.

Traumatic Brain Injury as a Risk Factor for Dementia and Alzheimer Disease: Critical Review of Study Methodologies.

Despite much previous research stating that traumatic brain injury (TBI) has been confirmed as a risk factor for dementia and Alzheimer disease (AD), findings from observational studies are mixed and are of low methodological quality. This review aimed to critically evaluate the methodologies used in previous studies. Relevant literature was identified by examining reference lists for previous reviews and primary studies, and searches in MEDLINE, PubMed, Google Scholar, and Research Gate. Sixty-eight identified reports, published between 1982 and August 2018, met inclusion criteria. Common methodological weaknesses included self-reported TBI (62%); poor TBI case definition (55%); low prevalence of TBI in samples (range 0.07-28.7%); reverse causality (86% moderate to high risk of reverse causality); not controlling for important confounding factors. There were also key areas of methodological rigor including use of individual matching for cases and controls (57%); gold standard dementia and AD criteria (53%); symmetrical data collection (65%); large sample sizes (max, 2,794,752); long follow-up periods and controlling of analyses for age (82%). The quality assessment revealed methodological problems with most studies. Overall, only one study was identified as having strong methodological rigor. This critical review identified several key areas of methodological weakness and rigor and should be used as a guideline for improving future research. This can be achieved by using longitudinal prospective cohort designs, with medically confirmed and well characterized TBI sustained sufficient time before the onset of dementia, including appropriate controls and informants, and considering the impacts of known protective and risk factors.

The Efficacy and Harms of Pharmacological Interventions for Aggression After Traumatic Brain Injury-Systematic Review.

Background: Aggression is a commonly reported problem following traumatic brain injury (TBI). It may present as verbal insults or outbursts, physical assaults, and/or property destruction. Aggressive behavior can fracture relationships and impede participation in treatment as well as a broad range of vocational and social activities, thereby reducing the individual's quality of life. Pharmacological intervention is frequently used to control aggression following TBI. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for aggression following TBI in adults. Methods: We reviewed studies in English, available before December 2018. 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 the severity of aggression and occurrence of harms. The secondary outcomes of interest were changes in quality of life, participation, psychological health (e.g., depression, anxiety), and cognitive function. Evidence quality was assessed using the Cochrane Risk of Bias tool and the Joanna Briggs Institute Critical Appraisal Instruments. Results: Ten studies were identified, including five randomized controlled trials (RCTs) and five case series. There were positive, albeit mixed, findings for the RCTs examining the use of amantadine in reducing irritability (n = 2) and aggression (n = 2). There were some positive findings favoring methylphenidate in reducing anger (n = 1). The evidence for propranolol was weak (n = 1). Individual analysis revealed differential drug response across individuals for both methylphenidate and propranolol. The less rigorous studies administered carbamazepine (n = 2), valproic acid (n = 1), quetiapine (n = 1), and sertraline (n = 1), and all reported reductions in aggression. However, given the lack of a control group, it is difficult to discern treatment effects from natural change over time. Conclusions: This review concludes that a recommendation for use of amantadine to treat aggression and irritability in adults following TBI is appropriate. However, there is a need for further well-designed, adequately powered and controlled studies of pharmacological interventions for aggression following TBI.

Efficacy and Harms of Pharmacological Interventions for Neurobehavioral Symptoms in Post-Traumatic Amnesia after Traumatic Brain Injury: A Systematic Review.

Many individuals in post-traumatic amnesia (PTA) following traumatic brain injury (TBI) experience neurobehavioral symptoms (NBS) in addition to disorientation and amnesia. These symptoms are associated with low rehabilitation engagement, self-inflicted harm, and risk of violence. The aim of this systematic review was to evaluate the efficacy and harms of pharmacological interventions for NBS in PTA following TBI in adults. Studies in English published before December 2017 were reviewed. Six databases were searched, with additional hand searching of key journals, clinical trials registries, and international drug regulators. Evidence quality was assessed using Joanna Briggs Institute Critical Appraisal Instruments. Thirteen studies were identified: three randomized controlled trials (RCTs), three cohort studies, and seven case series. In the RCTs, neither amantadine nor sertraline reduced NBS. Less rigorous studies reported reduced NBS in patients administered haloperidol, ziprasidone, carbamazepine, amitriptyline, desipramine, and varied neuroleptics. There is a paucity of well-designed, adequately powered and controlled studies of pharmacological interventions for NBS in PTA. More research is needed to provide evidence-based treatment recommendations and improve care.