Posts Tagged pharmacological
[REVIEW] Using the ICF framework to explore a multidisciplinary approach to fatigue following traumatic brain injury – Full Text
Posted by Kostas Pantremenos in Fatigue, TBI on January 24, 2024
Abstract
Background
Fatigue following a traumatic brain injury (TBI) is a complex, chronic symptom, which can significantly impact quality of life. Investigation into the types of fatigue addressed by the multidisciplinary team and consequent outcomes may assist clinicians to target their care. The use of health frameworks to explore such phenomena may increase a teams’ ability to incorporate multifaceted interventions. The objective of this paper is to profile and map the available evidence for fatigue management used for the TBI population onto the International Classification of Functioning, Disability, and Health framework.
Methods
A scoping review was conducted and included papers that described an intervention focussing on post-TBI fatigue and used fatigue-specific outcome measures with an adult population. Studies were collated and summarised, and key findings are presented.
Results
Forty-seven articles met the inclusion criteria. The results indicate that post-traumatic fatigue interventions in the literature are conducted by singular professions, that there is a strong focus on a body functions approach, and that there is a discrepancy between intervention intent and measurement.
Conclusion
Although there is variety in multidisciplinary fatigue treatment, further opportunities to develop interventions that target other health and function components, including activities and participation, environment, and personal factors, may enable a greater impact of fatigue management approaches. […]
[VIDEO] Understanding and Managing Spasticity in Poststroke Rehabilitation
Posted by Kostas Pantremenos in Spasticity, Video on January 11, 2024
The medical director of the Inpatient Rehabilitation Unit at Ascension Genesis Hospital talked about the management of poststroke spasticity and highlighted the importance of awareness, education, and early intervention. [WATCH TIME: 5 minutes]
WATCH TIME: 5 minutes
https://imasdk.googleapis.com/js/core/bridge3.609.1_en.html#goog_308621131PlayMute
“Spasticity is a word that most people have never heard of, but it means it’s a stiffness in the muscle—a velocity-dependent resistance to movement. With poststroke spasticity, you have to stretch. It is your medicine that you cannot miss and you have to take every day. Educating patients about potential poststroke spasticity and closely monitoring its development are crucial, as spasticity can manifest in diverse ways impacting individuals’ daily lives.”
Poststroke spasticity, a common complication, is associated with other signs and symptoms of the upper motor neuron syndrome, including agonist/antagonist co-contraction, weakness, and lack of coordination. These symptoms combined may result in impairments and functional issues that can predispose to costly complications for patients seeking treatment. According to a review previously published in Stroke, researchers suggest that the goal of managing poststroke spasticity should not only consider the reduction of muscle hypertonia but also the impact of the condition on function and well-being.1
Treatment interventions recommended by clinicians for patients with poststroke spasticity typically focus on peripheral and central strategies, including physical techniques to increase muscle length like stretching and pharmacological modulation. Despite limited comparative studies on the superiority of one method over another for poststroke spasticity, researchers have found that optimal management involves a combined and coordinated compendium of therapies.1 These combined recommendations for care encompass cost-effective pharmacological and surgical interventions as well as rehabilitative efforts for patients.
Harmony Sierens, MD, a physiatrist, recently sat down in an interview with NeurologyLive® to discuss how spasticity manifests poststroke, and why early awareness and education is essential for patients. Sierens, who also serves as the medical director at Ascension Genesis Inpatient Rehab Unit, spoke about the role that stretching plays in the management of poststroke spasticity, and why it is considered a crucial component of treatment. Additionally, she talked about how healthcare professionals effectively monitor and intervene early in cases of spasticity after brain or spinal cord injuries.
REFERENCES
1. Francisco GE, McGuire JR. Poststroke spasticity management. Stroke. 2012;43(11):3132-3136. doi:10.1161/STROKEAHA.111.639831
[Systematic review] Pharmacological interventions for the treatment of post-stroke fatigue – Full Text
Posted by Kostas Pantremenos in Fatigue, Pharmacological on December 10, 2023
Abstract
Background:
Post-stroke fatigue (PSF) affects around 50% of stroke survivors. Previous systematic reviews of randomized controlled trials found insufficient evidence to guide practice, but most excluded Chinese studies. Furthermore, their searches are now out-of-date.
Aims:
To systematically review and perform a meta-analysis of randomized placebo-controlled trials of pharmacological interventions for treating PSF.
Methods:
We screened Airitri, CNKI, VIP, CINAHL, ClinicalTrials.gov, CENTRAL, Cochrane Stroke Group Trial Register, EMBASE, EU Clinical Trial Register, ISRCTN, MEDLINE, PsycINFO, Wanfang, and WHO ICTRP up to 11 November 2022. Our primary outcome was fatigue severity. We conducted subgroup analysis by drug type and sensitivity analysis after excluding the trials at high risk of bias. Secondary outcomes included mood and quality of life.
Results:
We screened 33,297 citations and identified 10 published completed trials, 6 unpublished completed trials, and 6 ongoing trials. Pharmacological treatments were associated with lower fatigue severity at the end of treatment (10 published completed trials, 600 participants, pooled standardized mean difference (SMD) = −0.80, 95% confidence interval (CI): −1.29 to −0.31; I2 = 86%, p < 0.00001), but not at follow-up (265 participants, pooled SMD = −0.14, 95% CI: −0.38 to 0.10; I2 = 0, p = 0.51). However, these trials were small and had considerable risk of bias. Beneficial effects were seen in trials with low risk of bias on randomization, missing outcome data, and reporting bias. There were insufficient data on secondary outcomes for meta-analysis, but six trials reported improved quality of life.
Conclusion:
There is insufficient evidence to support a particular pharmacological treatment for PSF, thus current clinical guidelines do not require amendment.
Background
More than 15 million people have a stroke each year globally, of whom more than 30% are left with severe long-term disability.1 Between 25% and 85% of stroke survivors have post-stroke fatigue (PSF), which may persist for many years.2–5 There are important gaps in understanding the etiology of PSF.6 In 2023, the World Stroke Organization identified the lack of strong recommendations for PSF management.7 How to manage PSF is a priority for the Europe’s 2018–2030 Stroke Action Plan.8
Previous systematic reviews of PSF treatment generally sought studies only from English-language databases, though Wu et al.,9 who conducted a Cochrane review in 2014, included Chinese trials. Hinkle et al.6 included trials from 2000 to 2016, which was updated by Aali et al.10 to include published trials until January 2020, but these two reviews included only trials published in English. There are two reviews of individual Chinese herbal medicine interventions: Xu et al.11 reviewed trials of Astragalus membranaceus interventions up to November 2016 and Jin et al.12 reviewed randomized controlled trials (RCTs) of Buyang Huanwu Tang interventions up to October 2021, but there is no review of all Chinese herbal medicines. Furthermore, these reviews are now out-of-date. Therefore, a comprehensive and up-to-date review is needed to identify all trials (completed and published, completed but not published, and ongoing) of any pharmacological interventions for treating PSF, including trials published in Chinese. […]
[ARTICLE] Reversing the Ruin: Rehabilitation, Recovery, and Restoration After Stroke – Full Text
Posted by Kostas Pantremenos in REHABILITATION on April 6, 2023
Abstract
Purpose of Review
Stroke is a common cause of disability in aging adults. A given individual’s needs after stroke vary as a function of the stroke extent and location. The purpose of this review was to discuss recent clinical investigations addressing rehabilitation of an array of overlapping functional domains.
Recent Findings
Research is ongoing in the domains of movement, cognition, attention, speech, language, swallowing, and mental health. To best assist patients’ recovery, innovative research has sought to develop and evaluate behavioral approaches, identify and refine synergistic approaches that augment the response to behavioral therapy, and integrate technology where appropriate, particularly to introduce and titrate real-world complexity and improve the overall experience of therapy.
Summary
Recent and ongoing trials have increasingly adopted a multidisciplinary nature — augmenting refined behavioral therapy approaches with methods for increasing their potency, such as pharmaceutical or electrical interventions. The integration of virtual reality, robotics, and other technological advancements has generated immense excitement, but has not resulted in consistent improvements over more universally accessible, lower technology therapy.
Introduction
An estimated 7.6 million American adults have had a stroke, and projections show that by 2030, an additional 3.4 million will, a 20% increase in prevalence over the next 10 years [1, 2]. However, recent advancements have driven an age-adjusted decrease in death from stroke and complementary increase in demand for rehabilitation [3]. A given individual’s needs after stroke vary widely as a function of the stroke extent and location. Motor impairments are the most common [4], but post-stroke cognitive impairments have been estimated in as much as half of surviving adults [5, 6] and may include deficits in reasoning, attention [7, 8], memory [9], and language that significantly contribute to a reduced quality of life [10]. Mental health also has been identified as an important mediating factor for rehabilitation success [11, 12].
Post-stroke recovery is impacted by numerous activity-dependent mechanisms including axonal sprouting [13, 14, 15], dendritic spine elaboration [16, 17], and migration of subventricular stem cells to peri-infarct regions [18, 19, 20]. Synaptic plasticity is the dominant mechanism for recovery. Thus, the basic principles of behaviorally supported neuroplasticity apply; frequent, rigorous, specific exercises lead to recovery of function [21]. The standard of care for post-stroke rehabilitation remains characterized by task-specific and task-oriented training strategies facilitated by a clinician and deployed for 30–60 min per day for each domain (physical and cognitive-linguistic) in the acute phase and tapering over time as a function of recovery and ongoing access to services.
The goal of physiatric research is maximizing the effectiveness and efficiency of supported recovery. This work can be broadly classified in one of three ways. First is the development and evaluation of activities and strategies to facilitate behavioral modification. Second is identification and refinement of synergistic approaches to behavioral therapy that decrease the threshold for long-term potentiation and depression through direct manipulations like transcranial direct current stimulation (tDCS) [22, 23, 24] or pharmacological adjuncts [25, 26•]. Finally, there is considerable enthusiasm for the introduction of emerging technology, such as robotics, virtual reality (VR), and gamification for the enhancement of therapy, which offer promising ways of improving rehabilitation adherence. These innovations also allow rehabilitation specialists to introduce and titrate real-world complexity and multifaceted demands, particularly in the inpatient setting. Patients may use these tools in conjunction with other technologies. For example, a patient may engage in a gamified version of a therapy task, meaning it integrates elements like scoring points, rules, puzzles, and competition, typically to increase interest and engagement in the activity’s goal, but instead of moving a joystick or pressing keys, the interaction with the task is electromyographically directed, meaning the electrical activity in the patient’s muscle is the input used to interact with the task.
Here, we will summarize the recent evidence for novel behavioral strategies, synergistic approaches, and technological enhancements across three key domains of function: mobility, cognition, and language. Mobility research has been substantially strengthened by the bench to bedside pipeline. However, there is a relative dearth of cognitive rehabilitation studies targeting attention, executive function, and memory, let alone positive trials. Despite considerable interest, studies targeting post-stroke language rehabilitation, or the treatment of aphasia, are even more niche and, thus, that much more difficult to design and execute. For this reason, we have incorporated both meta-analyses and systematic reviews, which near-ubiquitously note the paucity of well-controlled, sufficiently powered clinical trials, and descriptions of select ongoing trials into our review in order to best reflect the leading edge of physiatry research.[…]
[Abstract] Can pharmacological, psychological and non-invasive brain stimulation interventions prevent depression after stroke? A cochrane review summary with commentary
Posted by Kostas Pantremenos in Depression on March 20, 2022
Abstract
Background: Depression is very common in patients after a stroke and it can impact recovery.
Objective: The Cochrane Review aimed to determine whether psychological therapy, pharmacological interventions, non-invasive brain stimulation, or their combination can prevent depression after stroke.
Methods: The population addressed were patients who suffered from a stroke and had no previous diagnosis of depressive disorders. Studies comparing pharmacological intervention to placebo, psychological therapy to usual care, and non-invasive brain stimulation to sham stimulation or usual care were included.
Results: Outcome information was available for nine pharmacological and two psychological trials, showing favorable treatment effects.
Conclusions: The available evidence suggests that pharmacological interventions and psychological therapy may prevent depression and improve mood after stroke. Although, the current evidence is of very low quality resulting in serious uncertainties about the estimates of effect observed.
Similar articles
- Pharmacological, psychological and non-invasive brain stimulation interventions for preventing depression after stroke.Allida S, Cox KL, Hsieh CF, House A, Hackett ML.Cochrane Database Syst Rev. 2020 May 11;5(5):CD003689. doi: 10.1002/14651858.CD003689.pub4.PMID: 32390167 Free PMC article.
- Pharmacological, psychological, and non-invasive brain stimulation interventions for treating depression after stroke.Allida S, Cox KL, Hsieh CF, Lang H, House A, Hackett ML.Cochrane Database Syst Rev. 2020 Jan 28;1(1):CD003437. doi: 10.1002/14651858.CD003437.pub4.PMID: 31989584 Free PMC article.
- Prevention of depression in adults with long-term physical conditions.Kampling H, Baumeister H, Bengel J, Mittag O.Cochrane Database Syst Rev. 2021 Mar 5;3(3):CD011246. doi: 10.1002/14651858.CD011246.pub2.PMID: 33667319 Free PMC article.
- Psychological therapies for treatment-resistant depression in adults.Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N.Cochrane Database Syst Rev. 2018 May 14;5(5):CD010558. doi: 10.1002/14651858.CD010558.pub2.PMID: 29761488 Free PMC article. Review.
- Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.Cox GR, Callahan P, Churchill R, Hunot V, Merry SN, Parker AG, Hetrick SE.Cochrane Database Syst Rev. 2012 Nov 14;11:CD008324. doi: 10.1002/14651858.CD008324.pub2.PMID: 23152255 Updated. Review.
[WEB] Does Constraint-Induced Movement Therapy Make Botox More Effective At Reducing Spasticity After Stroke??
Posted by Kostas Pantremenos in Constraint induced movement therapy CIMT, Pharmacological, REHABILITATION, Spasticity on November 18, 2021
by Scott Buxton
Spasticity is a common complication after stroke and is often very challenging to manage and many treatments are used to try and limit its effect on function and quality of life.
There are a number of different pharmacological and non-pharmacological treatments used to manage spasticity. These include botox and anti-spasticity drugs such as baclofen and benzodiazepines as well as rehab strategies including splinting, stretching, FES, exercise and constraint-induced movement therapy.
Further Your Knowledge of Stroke
Constraint-induced movement therapy and botox are often thought to be the two most useful and effective treatments for certain types of spasticity however the effects of combining the two during one treatment block has yet to be fully evaluated.
A new systematic review published in Cureus aimed to do just that, investigate the effectiveness of botox + CIMT by comparing the combination with botox + traditional therapy.
What is Constraint-Induced Movement Therapy?
Constraint-induced movement therapy or CIMT describes a package of different interventions designed to decrease he impact of stroke on the upper-limb function. It can be thought of as learned-nonuse.
The three major components of CIMT are:
- Repetitive, structure, practice intensive therapy in the more affect arm
- restraint of the less affected arm
- Application of behavioural techniques that improve functional use of the treatment
The treatment is usually indicated if the person who has suffered the stroke has some hand function, high motivation, minimal cognitive dysfunction and has the ability to walk whilst wearing the restraint.
The treatment is intense with participants wearing a mitt on the less-affected arm 90% of their waking hours and performing repetitive task-oriented training with the affected arm 6-7 hours per day over 10-15 consecutive weekdays.
Methods
Five databases were used for the literature search which took place at the end of January 2021. Individual searches took place for each database and the search strategies are available in abbreviated format within the article.
Studies were eligible for inclusion if they:
- were RCTs or quasi-experimental studies that combined the effects of constraint-induced movement therapy and botox A
- involved adolescent and adults with post-stroke spasticity scoring 1-3 on the modified Ashworth scale
- published between 2001-2020
- used the modified Ashworth scale as a primary outcome measure. With motor activity log, Fugl-Meyer assessment and Barthel index as secondary measures.
Studies were excluded if they involved lower limb spasticity, paediatric stroke or traumatic brain injury. Single-arm studies and non-human studies were also excluded. It is unclear if there were any language restrictions.
Two authors performed the screening, extraction and quality assessment phases of the review with a third available for consensus if required. PEDro was used for the quality assessment with Cochrane’s Risk of Bias 2.0 being used for the assessment of bias.
Both qualitative and quantitative analysis were performed including a meta-analysis. This was done using a random-effects model investigating the mean modified Ashworth scale changes in the elbow, wrist and finger joints as four weeks post-intervention time points to compare botox + constraint induce movement therapy with botox + conventional therapy.
Results
In total, after screening and full-text review only two studies were included within the review, both of which were RCTs, totalling 93 participants.
There was no table of participant characteristics therefore it is difficult to draw conclusions on confounding factors which may be influenced results.
Overall the studies were or reasonable quality according to PEDro and of low to moderate risk of bias although it was difficult to assess the reporting of results therefore caution needs to be applied.
Quick Summary of Botox + CIMT vs Botox + Conventional Therapy
- The results of the meta-analysis indicate no difference between groups at four weeks post-injection suggesting that CIMT does not influence outcomes after botox
- The two studies included within this review were small and there are some issues with reporting bias
The results of the meta-analysis indicate that there is no significant difference between botox + CIMT and botox + conventional treatment for reducing spasticity and improving function in the elbow, wrist or hand at four weeks post-injection.
There were some differences in ‘conventional’ treatment used between the two control groups but the numbers included in the studies are low making us unable to draw conclusions from this.
There are some issues with reporting bias in both studies meaning the applicability of these results to clinical practice is challenging. Overall the results of this systematic review should not change your clinical practice.
Open access – free to read
Read more in Physiopedia about Modified Ashworth Scale, Constraint Induced Movement Therapy and Spasticity#Management
[ARTICLE] Role of citicoline and choline in the treatment of post-stroke depression: an exploratory study – Full Text
Posted by Kostas Pantremenos in Depression, Pharmacological on November 12, 2021
Abstract
Objective
To compare selective serotonin reuptake inhibitors (SSRIs) and nootropic drugs in the reduction of anxiety and depressive symptoms in post-stroke patients.
Methods
This retrospective cohort study included patients diagnosed with post-stroke depression that were treated with either SSRIs or nootropic drugs (i.e. citicoline or choline alphoscerate). Depression and anxiety were assessed using the Hamilton Rating Scales. Statistical associations between the use of nootropic drugs and mood disorder improvements were determined by measuring assessment scores at 6-months.
Results
A total of 44 post-stroke patients with depression (aged 45–75 years) were enrolled in the study: 20 were treated with SSRIs and 24 received nootropic drugs. From baseline to follow-up, the SSRI group showed a large effect size with regard depression (success rate difference [SRD] 0.57; 95% confidence interval [CI] 0.21, 0.79) and anxiety (SRD 0.49; 95% CI 0.14, 0.74), whereas the nootropic group showed a small effect size for depression (SRD 0.16; 95% CI –0.17, 0.46) and a small effect size for anxiety (SRD 0.36; 95% CI –0.03, 0.62).
Conclusion
The administration of nootropic drugs could be a valid therapeutic strategy to manage post-stroke patients suffering from mild–moderate anxiety or anxious-depressive syndrome, but this requires further research.
Introduction
Stroke (ischaemic or haemorrhagic) has a severe impact on multiple functional domains and generally causes a greater range of disabilities, affecting the patient’s quality of life and generating negative emotional states.1 Indeed, if from the motor point of view some patients can return to their pre-stroke functional level, acquiring a greater autonomy in daily living activities, they can present other problems ranging from cognitive deficits to the difficulty in social reintegration.1
In the past, several studies were focused on motor disabilities and only recently are studies appearing on behavioural, cognitive and emotional impairment.2 Post-stroke depression (PSD) is a common neuropsychiatric condition in this class of patients, which is a potential mortality risk factor.3 Indeed, approximately 85% of patients with cerebrovascular disease suffer from PDS.4 The most common, but not exclusive, symptoms are apathy, fatigue, sleep disturbances and weight alterations, which compromise the quality of life of the subject, hindering their rehabilitation treatment and causing further disabilities and interpersonal problems.5,6 It is crucial to treat depressive symptoms in order to improve the disease recovery. Research has shown an improvement in mood disorders of patients with cerebrovascular diseases through the use of classic antidepressants.7
The onset of depressive symptoms depends on psychosocial and genetic factors, general vascular damage, the severity of the stroke and disability, cognitive impairment and on the interactions of other conditions.8 In the vast majority of cases, PSD appears in the first month after the stroke onset and tends to become chronic over time, interfering with the functional recovery.8 Patients can experience reduced compliance and increased resistance during rehabilitative treatments, because of their low self-esteem and lack of motivation.9,10
The association between PSD and the patient’s cognitive impairment has been shown to be different among the various types of cerebral infarction.9 Although patients with PSD have Mini Mental Examination State scores lower than non-PSD patients, the scores were significantly lower in patients with partial anterior circulation infarction compared with patients with lacunar circulation infarction or posterior circulation infarction.11 The association between cognitive impairment and depression is mutual because the relationship is very complex.12 However, antidepressant treatment stimulates the neurogenesis process and the benefits of treatment might not only cover depressive symptoms but also promote cognitive and motor recovery.13,14
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are frequently chosen for the treatment of depression. Notably, SSRIs are the first-choice drugs since their side-effects are generally well tolerated.15 Most research supports the efficacy of these antidepressants,13 but very few studies have evaluated the efficacy of other pharmacological therapies, such as psychostimulants.16 Indeed, drugs such as citicoline or choline alphoscerate could be used for the treatment of mood disorders in post-ischaemic stroke patients, as supportive drugs to the antidepressant treatment or as an alternative therapy in mild symptomatology.16
The aim of this study was to investigate whether a therapy based on nootropic drugs could be at least as effective in the reduction of anxiety and depressive symptoms as an antidepressant therapy in patients with PSD.[…]
[Preprint] Differences in outcomes following an intensive upper-limb rehabilitation programme for patients with common CNS-acting drug prescriptions – medRxiv
Posted by Kostas Pantremenos in Paretic Hand, Pharmacological, REHABILITATION on February 11, 2021
Abstract
Difficulty using the upper-limb is a major barrier to independence for many patients post-stroke or brain injury. High dose rehabilitation can result in clinically significant improvements in function even years after the incident, however there is still high variability in patient responsiveness to such interventions that cannot be explained by age, sex or time since stroke.
This retrospective study investigated whether patients prescribed certain classes of CNS-acting drugs – GABA agonists, antiepileptics and antidepressants-differed in their outcomes on the 3 week intensive Queen Square Upper-Limb (QSUL) programme.
For 277 stroke or brain injury patients (167 male, median age 52 years (IQR 21), median time since incident 20 months (IQR 26)) upper-limb impairment and activity was assessed at admission to the programme and at 6 months post-discharge, using the upper limb component of the Fugl-Meyer (FM), Action Research Arm Test (ARAT), and Chedoke Arm and Hand Activity Inventory (CAHAI). Drug prescriptions were obtained from primary care physicians at referral. Specification curve analysis (SCA) was used to protect against selective reporting results and add robustness to the conclusions of this retrospective study.
Patients with GABA agonist prescriptions had significantly worse upper-limb scores at admission but no evidence for a significant difference in programme-induced improvements was found. Additionally, no evidence of significant differences in patients with or without antiepileptic drug prescriptions on either admission to, or improvement on, the programme was found in this study. Whereas, though no evidence was found for differences in admission scores, patients with antidepressant prescriptions experienced reduced improvement in upper-limb function, even when accounting for anxiety and depression scores.
These results demonstrate that, when prescribed typically, there was no evidence that patients prescribed GABA agonists performed worse on this high-intensity rehabilitation programme. Patients prescribed antidepressants, however, performed poorer than expected on the QSUL rehabilitation programme. While the reasons for these differences are unclear, identifying these patients prior to admission may allow for better accommodation of differences in their rehabilitation needs.
Introduction
Stroke is the most common cause of long-term neurological disability worldwide (1). Currently, half of all people who survive a stroke are left disabled, with a third relying on others to assist with activities of daily living (2). A major contributor to ongoing physical disability is persistent difficulty in using the upper-limb (3). For many years it was believed that spontaneous upper-limb recovery occurred in the first 3 months following a stroke, with only small rehabilitation-induced improvements happening after this period (4). However, recent studies have demonstrated that with specific, high-dose training chronic patients can experience clinically significant improvements in upper-limb function (5–7). Yet despite these positive results, there is a degree of variability in patient outcomes that cannot be explained by impairment at admission or other patient characteristics (7). Identifying factors influencing this variability is therefore of high priority if similar high-intensity interventions are to be effectively developed.
There is an increasing wealth of literature, in both animals and humans, indicating that certain commonly used prescription drugs influence motor recovery following a brain lesion. Experimental findings from humans (8–12) indicate that selective serotonin reuptake inhibitors (SSRIs) may boost practice-dependent motor improvements, while animal experiments (13,14) and retrospective human studies (15,16) indicate activation at GABA receptors is detrimental to motor recovery. Though carefully matched placebo-controlled studies are the gold-standard for identifying the true effects of a given drug on motor recovery, these trials are costly and practically difficult. They must combine chronic drug administration with specific high-dose motor training (17).
Retrospective analysis that examines the relationship between drug prescriptions and patients’ response to rehabilitation programmes can provide a solution to some of these issues. In a naturalistic setting, prescriptions of common drugs come hand-in-hand with the co-morbidities they are aiming to treat, such as depression, epilepsy or spasticity. These issues may themselves impact on recovery, or interact with effects of the drug, making it difficult to draw conclusions about specific drug effects. However, using drug prescriptions to identify patients who systematically respond better or worse to a given intervention is the first step to singling out the causes of these disparities, and eventually leveraging these findings to improve interventions for all.
Another potential issue surrounding retrospective analysis of existing datasets is that, without pre-registration, researchers can be biased to make arbitrary analysis decisions motivated by results, rather than theory. A novel method, known as specification curve analysis (SCA), has been developed to tackle this problem (18). Using SCA, all reasonable variations of a possible analytical test assessing each hypothesis are run. Rather than examining the results of individual tests, the results across all tests are interpreted together to make a decision about whether to reject the null hypothesis (18).
[ARTICLE] Pharmacological management of long-term aggression secondary to traumatic brain injuries – Full Text
Posted by Kostas Pantremenos in Pharmacological on September 11, 2019
Abstract
Aggression is common after traumatic brain injuries (TBI) in acute and chronic settings. However, there is limited guidance regarding its assessment and effective management. Whilst a number of pharmacological options are available for long term treatment, the evidence base is not of an adequate strength to support a unified practice. This article will explore the currently available guidelines and recommendations for treating chronic aggression after TBIs and evaluate the evidence for its pharmacological management.
Introduction
Aggression is a long term neurobehavioural sequelae of TBIs with incidences quoted from 11.5-33.7%.1 In TBI patients, aggressive behaviour tends to be impulsive rather than premeditated and can manifest as episodic dyscontrol syndrome, disinhibition or exacerbated premorbid antisocial traits.2 The underlying mechanisms of aggression are complex allowing numerous and diverse interventions targeting various pathways.
In acute settings, Lombard and Zafonte (2005) describe non-pharmacological measures to manage aggression including environmental alterations and ensuring minimal or non-contact restraints. Screening for systemic causes, optimising pain control and patients’ sleep-wake cycle are also advocated. In the event of failed non-pharmacological treatment, Lombard and Zafonte (2005) recommend that medication choice should be tailored to individuals; with side effect profiles taken into consideration.3
For chronic aggression, psychological therapies are used as a first line with pharmacological interventions trialled in later stages.4 Psychological therapy options include cognitive behavioural therapy (CBT), behavioural management utilising operant learning theory and contingency management. However, a review by Alderman (2013) concluded that further evidence using scientific methods is needed to analyse these approaches.5 Comparatively, there is a diverse body of literature addressing long term pharmacological treatment although quality among studies are varied. This article will focus on the aetiology for chronic post TBI aggression, current management guidelines and the evidence for long term pharmacological interventions.[…]
TBI Rehabilitation 