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

ABSTRACT: 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.

SUBMITTER: Hicks AJ

PROVIDER: S-EPMC6895752 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Hicks Amelia J AJ Clay Fiona J FJ Hopwood Malcolm M James Amelia C AC Jayaram Mahesh M Perry Luke A LA Batty Rachel R Ponsford Jennie L JL

Frontiers in neurology 20191129

<b>Background:</b> 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 syste ...[more]

PMID: 31849802

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Project description:OBJECTIVE:The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI). METHODS:We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured. RESULTS:Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits. CONCLUSIONS:Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed. PROSPERO REGISTRATION NUMBER:CRD42016033140.

Project description:BackgroundFollowing traumatic brain injury (TBI) there is an increased prevalence of depression compared to the general population. It is unknown whether non-pharmacological interventions for depression are effective for people with TBI.ObjectivesTo investigate the effectiveness of non-pharmacological interventions for depression in adults and children with TBI at reducing the diagnosis and severity of symptoms of depression.Search methodsWe ran the most recent search on 11 February 2015. We searched the Cochrane Injuries Group Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), three other databases and clinical trials registers. Relevant conference proceedings and journals were handsearched, as were the reference lists of identified studies.Selection criteriaRandomised controlled trials (RCTs) of non-pharmacological interventions for depression in adults and children who had a TBI.Data collection and analysisTwo authors independently selected trials from the search results, then assessed risk of bias and extracted data from the included trials. The authors contacted trial investigators to obtain missing information. We rated the overall quality of the evidence of the primary outcomes using the GRADE approach.Main resultsSix studies met the inclusion criteria, with a total of 334 adult participants. We identified no studies that included children as participants. All studies were affected by high risk of bias due to a lack of blinding of participants and personnel; five studies were affected by high risk of bias for lack of blinding of outcome assessors. There was high or unclear risk of biases affecting some studies across all the Cochrane risk of bias measures.Three studies compared a psychological intervention (either cognitive behaviour therapy or mindfulness-based cognitive therapy) with a control intervention. Data regarding depression symptom outcome measures were combined in a meta-analysis, but did not find an effect in favour of treatment (SMD -0.14; 95% CI -0.47 to 0.19; Z = 0.83; P = 0.41). The other comparisons comprised of single studies of depression symptoms and compared; cognitive behaviour therapy versus supportive psychotherapy (SMD -0.09; 95% CI -0.65 to 0.48; Z = 0.30; P = 0.77); repetitive transcranial magnetic stimulation plus tricyclic antidepressant (rTMS + TCA) versus tricyclic antidepressant alone (SMD -0.84; 95% CI -1.36 to -0.32; Z = 3;19, P = 0.001); and a supervised exercise program versus exercise as usual (SMD -0.43; 95% CI -0.88 to 0.03; Z = 1.84; P = 0.07). There was very-low quality evidence, small effect sizes and wide variability of results, suggesting that no comparisons showed a reliable effect for any intervention.Only one study mentioned minor, transient adverse events from repetitive transcranial magnetic stimulation.Authors' conclusionsThe review did not find compelling evidence in favour of any intervention. Future studies should focus on participants with a diagnosed TBI and include only participants who have a diagnosis of depression, or who record scores above a clinical cutoff on a depression measure. There is a need for additional RCTs that include a comparison between an intervention and a control that replicates the effect of the attention given to participants during an active treatment.

Project description:ObjectiveNonsuicidal self-injury (NSSI), the deliberate, self-inflicted damage of bodily tissue without the intent to die, is associated with various negative outcomes. Although basic and epidemiologic research on NSSI has increased during the last 2 decades, literature on effective interventions targeting NSSI is still emerging. Here, we present a comprehensive, systematic review of existing psychological and pharmacological treatments designed specifically for NSSI, or including outcome assessments examining change in NSSI.MethodWe conducted a systematic search of PsycINFO, MEDLINE, and ERIC databases to retrieve relevant articles that met inclusion criteria; specifically, uncontrolled and controlled trials that 1) presented quantitative outcome data on NSSI, and 2) clearly differentiated NSSI from suicidal self-injury (SSI). Consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, definition of NSSI, we excluded studies examining populations with developmental or intellectual disabilities, or with psychotic disorders.ResultsSeveral interventions appear to hold promise for reducing NSSI, including dialectical behaviour therapy, emotion regulation group therapy, manual-assisted cognitive therapy, dynamic deconstructive psychotherapy, atypical antipsychotics (aripiprazole), naltrexone, and selective serotonin reuptake inhibitors (with or without cognitive-behavioural therapy). Nevertheless, there remains a paucity of well-controlled studies investigating treatment efficacy for NSSI.ConclusionsStructured psychotherapeutic approaches focusing on collaborative therapeutic relationships, motivation for change, and directly addressing NSSI behaviours seem to be most effective in reducing NSSI. Medications targeting the serotonergic, dopaminergic and opioid systems also have demonstrated some benefits. Future studies employing controlled designs as well as a clear delineation of NSSI and SSI will improve knowledge regarding treatment effects.

Project description:Background: Mild traumatic brain injury (mTBI) results from an external force to the head or body causing neurophysiological changes within the brain. The number and severity of symptoms can vary, with some individuals experiencing rapid recovery, and others having persistent symptoms for months to years, impacting their quality of life. Current rehabilitation is limited in its ability to treat persistent symptoms and novel approaches are being sought to improve outcomes following mTBI. Neuromodulation is one technique used to encourage adaptive neuroplasticity within the brain. Objective: To systematically review the literature on the efficacy of neuromodulation in the mTBI population. Method: A systematic review was conducted using Medline, Embase, PsycINFO, PsycARTICLES and EBM Review. Preferred Reporting Items for Systematic Reviews and the Synthesis Without Meta-analysis reporting guidelines were used and a narrative review of the selected studies was completed. Fourteen articles fulfilled the inclusion criteria which were published in English, investigating an adult sample and using a pre- and post-intervention design. Studies were excluded if they included non-mild TBI severities, pediatric or older adult populations. Results: Thirteen of fourteen studies reported positive reductions in mTBI symptomatology following neuromodulation. Specifically, improvements were reported in post-concussion symptom ratings, headaches, dizziness, depression, anxiety, sleep disturbance, general disability, cognition, return to work and quality of life. Normalization of working memory activation patterns, vestibular field potentials, hemodynamics of the dorsolateral prefrontal cortex and excessive delta wave activity were also seen. The studies reviewed had several methodological limitations including small, heterogenous samples and varied intervention protocols, limiting generalisability. Further research is required to understand the context in which neuromodulation may be beneficial. Conclusions: While these positive effects are observed, limitations included unequal representation of neuromodulation modalities in the literature, and lack of literature describing the efficacy of neuromodulation on the development or duration of persistent mTBI symptoms. Better clarity regarding neuromodulation efficacy could have a significant impact on mTBI patients, researchers, clinicians, and policy makers, facilitating a more productive post-mTBI population. Despite the limitations, the literature indicates that neuromodulation warrants further investigation. PROSPERO registration number: CRD42020161279.

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

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

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