Use of Olanzapine to Treat Agitation in Traumatic Brain Injury: A Series of N-of-One Trials

Phyland, Ruby K; McKay, Adam; Olver, John; Walterfang, Mark; Hopwood, Malcolm; Ponsford, Michael; Ponsford, Jennie Louise

doi:10.1089/neu.2022.0139

Cited by 9 publications

(5 citation statements)

References 73 publications

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“…More dedicated, well-designed prospective research is needed, but early attempts have proven challenging because of the nature of the TBI patient population. 74 , 75 Pre-clinical studies thus offer a highly controlled environment in which the potential benefits and harms can be systematically explored. Indeed, given the strength of data pre-clinically regarding potential harms of antipsychotic administration, recent clinical guidelines have included the citation of seminal pre-clinical works as part of the rationale to exercise caution and minimization when prescribing antipsychotic medications post-TBI.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury

Race,

Moschonas,

Cheng

et al. 2023

Neurotrauma Reports

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Sixty-nine million traumatic brain injuries (TBIs) are reported worldwide each year, and, of those, close to 3 million occur in the United States. In addition to neurobehavioral and cognitive deficits, TBI induces other maladaptive behaviors, such as agitation and aggression, which must be managed for safe, accurate assessment and effective treatment of the patient. The use of antipsychotic drugs (APDs) in TBI is supported by some expert guidelines, which suggests that they are an important part of the pharmacological armamentarium to be used in the management of agitation. Despite the advantages of APDs after TBI, there are significant disadvantages that may not be fully appreciated clinically during decision making because of the lack of a readily available updated compendium. Hence, the aim of this review is to integrate the existing findings and present the current state of APD use in pre-clinical models of TBI. The studies discussed were identified through PubMed and the University of Pittsburgh Library System search strategies and reveal that APDs, particularly those with dopamine 2 (D 2 ) receptor antagonism, generally impair the recovery process in rodents of both sexes and, in some instances, attenuate the potential benefits of neurorehabilitation. We believe that the compilation of findings represented by this exhaustive review of pre-clinical TBI + APD models can serve as a convenient source for guiding informed decisions by critical care clinicians and physiatrists contemplating APD use for patients exhibiting agitation.

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Section: Discussionmentioning

confidence: 99%

Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury

Race,

Moschonas,

Cheng

et al. 2023

Neurotrauma Reports

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“…[92][93][94] Unlike typical agents such as haloperidol, the atypical antipsychotic olanzapine has not demonstrated such deleterious effects on motor or cognitive outcomes 90 and possesses a more favorable safety profile. [95][96][97] In a recent placebo-controlled trial reported as an n-of-1 series, 98 11 agitated participants in PTA received oral olanzapine (n = 5) or placebo (n = 6) for the duration of PTA, beginning at a dose of 5 mg/d and titrated every 3 to 4 days to a maximum dose of 20 mg/d. A significant decrease in agitation with moderate to very large effect (Tau-U effect size = 0.37-0.86) was observed for 3 of 5 participants receiving olanzapine, while no significant reduction in agitation was observed for any participant receiving placebo.…”

Section: Pharmacological Interventions During Ptamentioning

confidence: 99%

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part I: Posttraumatic Amnesia

Ponsford

Trevena-Peters²,

Janzen³

et al. 2023

Journal of Head Trauma Rehabilitation

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Introduction: Posttraumatic amnesia (PTA) is a common occurrence following moderate to severe traumatic brain injury (TBI) and emergence from coma. It is characterized by confusion, disorientation, retrograde and anterograde amnesia, poor attention and frequently, agitation. Clinicians and family need guidelines to support management practices during this phase. Methods: An international team of researchers and clinicians (known as INCOG) met to update the INCOG guidelines for assessment and management of PTA. Previous recommendations and audit criteria were updated on the basis of review of the literature from 2014. Results: Six management recommendations were made: 1 based on level A evidence, 2 on level B, and 3 on level C evidence. Since the first version of INCOG (2014), 3 recommendations were added: the remainder were modified. INCOG 2022 recommends that individuals should be assessed daily for PTA, using a validated tool (Westmead PTA Scale), until PTA resolution. To date, no cognitive or pharmacological treatments are known to reduce PTA duration. Agitation and confusion may be minimized by a variety of environmental adaptations including maintaining a quiet, safe, and consistent environment. The use of neuroleptic medications and benzodiazepines for agitation should be minimized and their impact on agitation and cognition monitored using standardized tools. Physical therapy and standardized activities of daily living training using procedural and errorless learning principles can be effective, but delivery should be tailored to concurrent levels of cognition, agitation, and fatigue. Conclusions: Stronger recommendations regarding assessment of PTA duration

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“…In fact, such studies often make use of samples from a single individual or strain of mice and so, from a biological standpoint, they are, by their nature, assuming that insights from a single individual can shed light on very general biological questions. There are many recent examples of N-of-1 studies, which we will not review exhaustively here (Gabler et al 2011;Nikles et al 2022;Samuel et al 2022;Kronish et al 2018), but rather simply emphasize that they are growing in number and sophistication (Lamb et al 2022;Phyland et al 2022;Kim et al 2019). The third is that the execution of N-of-1 trials focusing on important physiologic endpoints can be greatly enhanced with emerging digital health-based monitoring devices (such as the Apple watch and continuous glucose monitors), survey instruments made available through smart phone apps, and largely pain-free and convenient methods for obtaining https://doi.org/10.1017/pcm.2022.15 Published online by Cambridge University Press blood, urine, stool and saliva samples (Izmailova, Wagner, and Perakslis 2018;Enderle, Foerster, and Burhenne 2016).…”

Section: Human Biology and Legacy Clinical Trialsmentioning

confidence: 99%

Section: Basic N-of-1 Trial Designsmentioning

confidence: 99%

Exploring human biology with N-of-1 clinical trials

Schork

Beaulieu‐Jones

Liang³

et al. 2023

Camb. prisms Precis. med.

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Studies on humans that exploit contemporary data-intensive, high-throughput 'omic' assay technologies, such as genomics, transcriptomics, proteomics, and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual's distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on 'precision' medicine. This review's purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real time care to the very individuals who are seeking attention for their health concerns in the first place.

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Use of Olanzapine to Treat Agitation in Traumatic Brain Injury: A Series of N-of-One Trials

Cited by 9 publications

References 73 publications

Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury

Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part I: Posttraumatic Amnesia

Exploring human biology with N-of-1 clinical trials

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