Overview of pharmacological interventions after traumatic brain injuries: impact on selected outcomes

ABSTRACT

The purpose of this study was to conduct an overview of systematic reviews (SRs) to appraise the published evidence related to pharmacological interventions after traumatic brain injury (TBI). Searches were conducted with Medline, Embase, PsycINFO, Web of Science, PubMed. 780 retrieved SRs underwent a two-level screening to determine inclusion. Data extracted included participant characteristics, TBI severity, study design, pharmacological interventions, and outcomes. SRs were assessed for methodological quality by using the AMSTAR measurement tool. After removing duplicates, 166/780 SRs published between 1990-2017 were reviewed, 62 of which met inclusion criteria. More than 90 drugs and 22 substance-classes were extracted. Most medications were administered during the acute stage. Mild TBI was included in 3% of the SRs. Physiological outcomes comprised 45% of the SRs, primarily mortality. Activities of daily living (ADLs) outcomes constituted 22% of the SRs followed by cognition (13%) and psychological/behavioral outcomes (13%). Only 7% of the SRs assessed adverse events. Inconsistencies in definitions, methods, and heterogeneity of instruments used to measure treatment response were noted. Only a third of the SRs had high methodological quality. Most SRs had heterogeneous TBI samples, outcomes, or methodologies making it difficult to synthesize findings into recommended guidelines. This study demonstrated a need for adequately powered and rigorous randomized clinical trials (RCTs) to provide generalizable evidence on the effectiveness of pharmacologic interventions for TBI. PROSPERO Registration: CRD42015017355

KEYWORDS:

• Systematic review
• meta-analysis
• traumatic brain injury
• pharmacological interventions

Acknowledgments

The authors want to thank the contribution of taskforce members, Drs Zach Bayer and Pallavi Sood, who were critical in different components of the project but could not participate in its entire process. Thank you to Dr. Dawn Ehde for her careful review of this manuscript. This manuscript was developed with the generous support of the American Congress of Rehabilitation Medicine Measurement Networking Group. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

This study was conceived through a collaborative effort from the members from the Applied Cognition TBI Taskforce from the American Congress of Rehabilitation Medicine Measurement Networking Group. The taskforce members contributed equally to the intellectual content and a priori protocol design and implementation of this manuscript as well as the data abstraction. Dr. Kim is the leading author of this manuscript and she conceived the manuscript with the significant assistance of the co-authors. Dr. Mortera contributed to the introduction, results, and discussion sections of the manuscript. Dr. Hoffecker was responsible in developing the search strategies and citations database. Dr. Kim was responsible in performing most of the statistical synthesis. Drs. Hu and Herrold were responsible for the pharmacological evaluation and synthesis. Dr. Kim and Mr. Machtinger developed and organized the database. Drs. Kim, Herrold, Hoffecker, King, Krishnan, Mortera and Terhorst were key authors in evaluating the main outcomes. Dr. Terhorst contributed to the extraction and synthesis of the designs of the included studies. Dr. Krishnan and Mr. Machtinger were responsible for the critical appraisal synthesis. Dr. Heyn assisted with consultations and mentorship in all phases of the study. All authors contributed to the manuscript and approved the final version of the manuscript.

Declaration of interest statement

The authors have no conflict of interests to disclose.

Previous presentations

Preliminary results were presented as a poster and in a symposium at the 2017 Annual Meeting of the American Congress of Rehabilitation Medicine, Atlanta, Georgia.

Protocol and registration

PROSPERO International prospective register of systematic reviews (CRD4201501735). This protocol can be accessed at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=17355

Supplementary material

Supplemental data for this article can be accessed here.