Posts Tagged pharmacological

[WEB SITE] Can Ritalin Help Mitigate Brain Injury Symptoms?


My 54-year-old husband sustained a TBI when he fell asleep at the wheel while driving and hit a tree. The doctors say that he damaged all four parts of his brain. It’s been more than one and a half years and he’s still totally dependent on me to take care of him. Do you think Ritalin would help stimulate his brain?


Methylphenidate (Ritalin) is one of the commonly used brain stimulants in people who have suffered traumatic brain injury. It increases chemicals in the brain that have a stimulating effect (norepinephrine and dopamine).

After traumatic brain injury, doctors commonly prescribe Ritalin for low arousal or initiation, poor attention and concentration, depression, and slow processing speed. There is research that shows that Ritalin may speed recovery early after moderate to severe TBI. There is also research showing that Ritalin increases mental processing speed after TBI, which can improve memory function in some people.

All medications have side effects and the risks need to be weighed against possible benefits. One of the good things about the standard formulation of Ritalin is that it is short acting so if side effects occur they wear off in a few hours. Some potential side effects include keeping you up at night (if taken too close to bedtime), decreased appetite, headache, irritability, and paranoia.

In your husband’s case, his doctor needs to look at why he is so dependent. If arousalattention, and/or initiation are playing a significant role, a stimulant can be considered. Careful monitoring for effects and/or side effects is needed when starting this medication and it should only be done by a doctor who has experience in caring for people with traumatic brain injury. Ritalin and most stimulants are controlled substances and will require frequent visits to the doctor for prescriptions.

Source: Can Ritalin Help Mitigate Brain Injury Symptoms?

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[ARTICLE] Pharmacological interventions for traumatic brain injury – Full Text 

Psychostimulants, antidepressants, and other agents may speed the recovery of patients suffering from the functional deficits that follow an insult to the brain.

Traumatic brain injury is common in North America and has dramatic and wide-ranging effects on survivors’ quality of life. Those who survive traumatic brain injury may experience anxiety, agitation, memory impairments, and behavioral changes. When managing the immediate and long-term consequences of such injuries, clinicians have many pharmacological options, including psychostimulants, antidepressants, antiparkinsonian agents, and anticonvulsants. These and other agents can play a role in managing the neuropsychiatric, neurocognitive, and neurobehavioral sequelae of injury to the brain.

Traumatic brain injury (TBI) is commonly defined as an insult to the brain from an external force that causes temporary or permanent impairment in functional, psychosocial, or physical abilities.1 It is a significant cause of morbidity and mortality, and the leading cause of death and disability among young adults.

Common causes of TBI include motor vehicle accidents, falls, sports injuries, and violence,[1] and it is recog­nized increasingly in war zone injury.[2] In the US, approximately 2 million people will sustain a TBI each year, one-quarter of whom will require hospitalization, leading to a conservative estimate of direct and indirect costs of $50 billion to $100 billion annually.[3]

With advances in the management of head trauma, an increasing number of patients are surviving with residual neurological impairments. A National Institute of Health panel estimates that 2.5 to 6.5 million Americans currently live with TBI-related disabilities.[4]

The effective treatment of TBI requires input from multiple disciplines and professions starting at the time of injury and continuing through the rehabilitation phase.

Despite the prevalence and cost of TBI-related disabilities there is a paucity of literature reviewing modern approaches to pharmacotherapy. There is, however, growing evidence that medications may speed recovery by enhancing some neurological functions without impact­ing others.

Pharmacotherapy is in­creasingly being used in both the subacute (less than 1 month post-TBI) and chronic (more than 1 month post-TBI) phases.

Disabilities arising from TBI that have a direct impact on functioning and rehabilitative potential can be broadly classified into four main categories: decreased level of consciousness (LOC), and neuropsychiatric, neurocognitive, and neurobehavioral sequelae.5-8 Decreased level of consciousness refers to a diverse range of clinical states including coma, vegetative states, akinetic mutism, and locked-in states.

Neuropsychiatric symp­toms may present as mood disorders, posttraumatic stress disorder, and personality changes characterized by disinhibition and egocentricity. Neurocognitive injuries vary, but most frequently involve impaired attention, memory, and executive functioning.

Neurobehavioral deficits distinct from neuropsychiatric sequelae may take the form of irritability, hyperexcitability, nervousness, disinhibition, poor impulse control, restlessness, and aggression, with aggression and agitation seen in as many as 30% of brain-injured patients.[5-8]

Depending on the location of in­jury, damage can occur to a variety of neurotransmitter networks critical to cognitive processes. Investigation has focused on the loss of dopaminergic neurons that regulate executive functioning, as well as deficits in norepinephrine and acetylcholine, which limit attention—a critical function for effective rehabilitation.[9]

Fortunately, a number of pharmacological interventions show promise in helping patients cope with these losses and deficits.

Although insufficient evidence exists to establish guidelines for optimal pharmocotherapy, medications may be used to support recovery. Examples are shown in the accompanying Table, which summarizes the pharmacological approaches discussed in more detail below.

When problematic TBI symptoms are identified, clinicians can use this information to determine pharmacological options and integrate them with nonpharmacological options such as physical therapy, occupational therapy, physiatry, and the patient’s support network.

Planning a pharmacological intervention strategy
The decision to use pharmacological intervention should be the result of multidisciplinary collaboration and made with the patient or his or her substitute decision maker. Goals of therapy should be clarified, and outcomes and adverse events should be reliably tracked, particularly so medications that are ineffective or cause adverse events can be discontinued and unnecessary polypharmacy can be avoided.

Selecting the most appropriate agent requires careful analysis of the neurological disabilities present, the nature of the underlying lesion, and the time elapsed since the injury.

Psychostimulants such as methylpheni­date are most commonly used to treat attention deficit hyperactivity disorder (ADHD), a condition that involves problems with executive functioning and can be characterized as similar to brain injury both in terms of symptoms and neurotransmitter aberrations.[10]

Although the complete mechanism of action of methylphenidate remains unknown, this agent is thought to bind dopamine transporters, thereby blocking reuptake and increasing extracellular dopamine levels, particularly in the frontal cortex.[11] It is also thought to increase norepinephrine and serotonin levels.

In the majority of studies, methylphenidate has been administered  twice daily, either at a fixed dose of 10 to 15 mg or at a dose of 0.3 mg/kg.[12-15]

In the acute phase after a TBI, methylphenidate-treated patients dem­onstrated better attention, concentration, and performance on motor memory tasks at 1 month, but these benefits did not persist at 3 months. Thus, it has been suggested that while methyl­phenidate may shorten recovery time, it does not change morbidity.[12]

In the chronic phase after a TBI, patients have reported improvements in mood, work performance, and alertness, with more limited evidence suggesting an improvement of fluency and selective attention.

The impact of methylphenidate on chronic attention is more ambiguous: one study suggests improvement in long-term processing speed and attention to tasks but not increased sustained attention or decreased susceptibility to distraction.[12]

Two separate studies have suggested methylphenidate is effective in the treatment of agitation and sei­zures,[16,17] while another demonstrated no neurobehavioral benefit.[18]

Despite the accumulation of controlled clinical trials, there is no consensus on the use of stimulants in treating TBI-induced impairments in arousal and motor activity.

It should be noted that one recent review concluded “at present there is insufficient evidence to support routine use of methylphenidate or other amphetamines to promote recovery from TBI,”[19] while another review noted that at least 10 clinical trials have demonstrated a role for methylpheni­date in both adult and pediatric brain injury patients suffering from neurocognitive deficits, particularly in attention, memory, cognitive processing, and speech.[20]

Methylphenidate has a quick onset of action and relatively benign side effect profile, and we believe it to be useful in both the acute and chronic phase of TBI.

Despite potentially severe consequenc­es, post-TBI psychiatric sequelae are underdiagnosed and undertreated. Fortunately, current evidence suggests that antidepressants can be used to manage both neuropsychiatric and additional neurological deficits persisting from brain injury.

Selective serotonin reuptake inhi­bitors (SSRIs) have been found useful in treating behavioral syndromes in TBI patients, particularly in the subacute stages of recovery[21] but also in chronic settings.

The majority of studies suggest that SSRIs improve neurobehavioral, neurocognitive, and neuropsychiatric deficits, specifically agitation, depression, psychomotor retardation, and recent memory loss; however, most data originates from nonrandomized trials.

Sertraline administered at an average dose of 100 mg daily for 8 weeks has been found to be beneficial for agitation, depressed mood, and deficits in psychomotor speed and recent memory; shorter treatment durations have demonstrated no benefit.[21]

Similarly, 60 mg daily of fluoxetine for 3 months was shown to be effective in the treatment of obsessive-compulsive disorder caused by brain injury.[22] Finally, paroxetine or citalopram, at a dose of 10 to 40 mg daily, was shown by another study to be equally effective in the treatment of pathological crying.[23] None of the re­viewed studies addressed neurocognitive deficits.

The highest concentration of serotonergic and adrenergic fibres is located near the frontal lobes, the most common site of traumatic contusion.[24]

Consequently, these fibres are commonly injured in TBI, suggesting that newer antidepressants with effects on both norepinephrine and serotonin, such as mirtazapine and venlafaxine, may also be effective in the treatment of TBI sequelae; however, clinical data with these agents in TBI is lacking.

Similarly, bupropion increases both dopamine and norepinephrine levels and is a weak inhibitor of serotonin reuptake. At 150 mg daily, this agent has been useful in treating restlessness.[25]

Antiparkinsonian drugs
The antiparkinsonian drugs amantadine, bromocriptine, and levodopa combined with carbidopa (e.g., Sine­met) have varied mechanisms of action, but all ultimately serve to increase dopamine levels in the brain.

Amantadine acts presynaptically to enhance dopamine release or inhibit its reuptake, and can act postsynaptically to increase the number, or alter the configuration of, dopamine re­ceptors.[26] It is also a noncompetitive NMDA receptor antagonist and may provide protection against possible glutamate-mediated excitotoxicity in the context of TBI.[27]

Bromocriptine is a dopamine receptor agonist affecting primarily D2 receptors and to a lesser extent D1 receptors.[28] The use of levodopa and carbidopa in combination directly increases dopamine levels: levodopa becomes dopamine once de­carboxylated, while carbidopa inhibits L-amino decarboxylase, allowing levodopa to reach the central nervous system.[28]

Multiple studies of amantadine at a dose of 100 to 300 mg daily have suggested its effectiveness in both the acute and chronic care phases after TBI, particularly in diffuse, frontal, or right-sided brain injury.

Currently, the evidence suggests neurocognitive or neurobehavioral deficits, particularly cognition difficulties and agitation, are primary indications for amantadine use.[26,29,30]

Amantadine-treated patients demonstrated improvements in motivation; decreased level of apathy; increased attention, concentration, and alertness; improved executive functioning; decreased processing time; reduced agitation, distractibility, fatigue, aggression, and anxiety.

In addition, patients treated with amantadine demonstrated changes in outcome LOC, specifically improved arousal and LOC as measured by the Glasgow Coma Scale. Interestingly, one study also suggested decreased mortality.[31] To date, no study has shown an improvement in memory.

Three case reports using 5 to 45 mg of bromocriptine daily,[32] and one study using a combination of 100 mg of bromocriptine with 100 mg of ephedrine,[33] showed improvement in akinetic mutism, while another study using 5 mg of bromocriptine combined with sensory stimulation led to improvements in patients with vegetative or minimal consciousness.[34]

The evidence is similarly limited for levidopa and carbidopa medications where nonrandomized studies suggest that they might be useful in the chronic phase of TBI with diffuse injury and persistent vegetative state.[35]

Combining agents has also been tried in one study that found improvements in neuropsychiatric deficits with the daily administration of 25 mg/200 mg of levodopa/carbidopa three times daily, 250 mg of amantadine, and 5 mg of bromocriptine twice daily.[36]

Anticonvulsants have been used with varying results for treating symptoms of TBI. Valproic acid, for example, enhances inhibitory control mediated by the neurotransmitter GABA, thereby promoting general central nervous system stabilization, but findings thus far have been mixed.

Investigations utilizing 600 to 2250 mg of valproic acid daily (resulting in serum levels of 40 to 100 µg/mL), have demonstrated positive neurocognitive effects, in­cluding improved recent memory and problem-solving, as well as ameliorating neuropsychiatric and neuro­behavioral symptoms such as depression, mania, destructive and aggressive behavior, restlessness, disinhibition, impulsivity, lability, and alertness.[37-41]

Conversely, one control­led trial found valproic acid negatively impacted decision-making speed, and another suggested an increased mortality rate with valproic acid use.[37-41]

Other agents
Modafinil is a vigilance-promoting drug commonly used to treat narcolepsy and idiopathic hypersomnia, illnesses that can present with symptoms similar to those seen in TBI: excessive daytime sleepiness, inattention, and decreased ability to perform social activities.

The precise mechanism of action remains unknown, although it is believed that modafinil can inhibit GABA or increase glutamate levels in the nondopaminergic anterior hypothalamus, hippocampus, and amygdale.[42,43]

Two studies that investigated the role of modafinil in chronic TBI showed an improvement in neurocognitive deficits, specifically memory and attention, as well as improving daytime somnolence at doses between 100 and 400 mg.[44,45]

Four randomized control trials examining the use of beta-blockers, specifically propranolol and pindolol, have demonstrated beneficial effects on neurobehavioral symptoms of ag­gression and agitation in both the chronic and subacute phase. This class of drugs deserves further attention for the management of both neuropsychiatric and neurobehavioral sequelae of TBI.[46]

Neuroleptics are being used in­creasingly in the setting of delirium, and one might consider using them in an attempt to allow the brain to recalibrate neurotransmitter levels. However, it should be noted that there is some evidence that dopamine blockade may negatively affect recovery.[47,48]

There are also a number of animal studies examining drugs that have the potential to adversely affect brain recovery following TBI. These studies typically use a stroke model, so generalizing to TBI may not be possible.

Nevertheless, the evidence currently does not support the use of neuro­leptics, benzodiazepines, phen­y­toin, prazosin, trazodone, and similar agents because of their potential adverse effect on recovery, presumably through the impacts they have on neurotransmitters such as dopamine, norepinephrine, or GABA.[49-51]

Preliminary evidence suggests cho­linesterase inhibitors such as don­epezil may improve long-term cognitive outcomes, particularly in domains such as memory and attention when administered early, and further in­vestigation with these agents is also warranted.[52,53]

Finally, antiandrogenic medications, such as estrogen and medroxyprogesterone, may have a role to play in reducing inappropriate sexual be­havior in patients with TBI. In a case study and one small trial, these drugs demonstrated effectiveness.[54]

The nature of TBI sequelae, whether psychiatric, cognitive, or behavioral, is poorly understood. Likewise, the use of pharmacological interventions to improve symptoms, function, and outcome is still under development.

There are, however, a number of agents that inspire optimism. When treating neurological deficits medically, there is evidence to support the tailored use of these agents for particular TBI clinical scenarios. The timing and nature of symptoms, along with wheth­er agents are administered in the acute or chronic phase after TBI, are all relevant factors for determining proper use.

With insufficient evidence to establish guidelines for optimal treatment, care must be taken when choosing pharmacological interventions for TBI.

If the decision is made to use medications to promote TBI recovery or treat its attendant disabilities, clinicians should thoroughly document the goals of pharmacotherapy and closely monitor for side effects. Future studies will undoubtedly add to the clinician’s armamentarium for the care of TBI patients.

Competing interests
None declared.


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25. Teng C, Bhalerao S, Lee A, et al. The use of buproprion in the treatment of restlessness after a traumatic brain injury. Brain Inj 2001;15:463-467.
26. Schneider W, Drew-Cates J, Wong T, et al. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: An initial double-blind placebo-controlled study. Brain Injury 1999;13:863-872.
27. Kraus M, Maki P. The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic brain injury. Brain Inj 1997;11:455-460.
28. Zafonte R, Lexell J, Cullen N. Possible applications for dopaminergic agents following traumatic brain injury: Part 1. J Head Trauma Rehabil 2000;15:1179-1182.
29. Meythaler J, Brunner R, Johnson A, et al. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: A pilot double-blind randomized trial. J Head Trauma Rehabil 2002;31:300-313.
30. Zafonte R, Watanabe T, Mann N. Amantadine: A potential treatment for the minimally conscious state. Brain Inj 1998;12:617-621.
31. Saniova B, Drobny M, Kneslova L, et al. The outcome of patients with severe head injuries treated with amantadine sulphate. J Neur Transm 2004;111:511-514.
32. Crismon M, Childs A, Wilcox R, et al. The effect of bromocriptine on speech dysfunction in patients with diffuse brain injury (akinetic mutism). Clin Neuropharmacol 1988;11:462-466.
33. Anderson B. Relief of akinetic mutism from obstructive hydrocephalus using bromocriptine and ephedrine. J Neurosurg 1992;76:152-155.
34. Passler M, Riggs R. Positive outcomes in traumatic brain injury-vegetative state: Patients treated with bromocriptine. Arch Phys Med Rehabil 2001;82:311-315.
35. Haig A, Ruess J. Recovery from vegetative state of six months’ duration associated with Sinemet (levodopa/carbidopa). Arch Phys Med Rehabil 1990;71:1081-1082.
36. Karli D, Burke D, Kim H, et al. Effects of dopaminergic combination therapy for frontal lobe dysfunction in traumatic brain injury rehabilitation. Brain Inj 1999;13:63-68.
37. Wroblewski B, Joseph A, Kupfer J, et al. Effectiveness of valproic acid on destructive and aggressive behaviours in pa­tients with acquired brain injury. Brain Inj 1997;11:37-47.
38. Massagli T. Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: Implications for use in traumatic brain injury. Arch Phys Med and Rehabil 1991;72:219-225.
39. Dikmen S, Machamer J, Winn H, et al. Neuropsychological effects of valproate in traumatic brain injury. Neurology 2000;54:895-902.
40. Chatham-Showalter P, Kimmel DN. Agitated symptom response to divalproex following acute brain injury. J Neuropsychiatry Clin Neurosci 2000;12:395-397.
41. Kim E, Humaran T. Divalproex in the management of neuropsychiatric complications of remote acquired brain injury. J Neuropsychiatry Clin Neurosci 2002;14:202-205.
42. Lin J, Hou Y, Jouvet M. Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos im­muno­cytochemistry in the cat. Proc Natl Acad Sci U S A 1996;93:14128-14133.
43. Ferraro L, Antonelli T, Tanganelli S. The vigilance promoting drug modafinil in­creases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: Prevention by local GABAA receptor blockade. Neuropsychopharmacology 1999;20:346-356.
44. Saletu B, Saletu M, Grunberger J, et al. Treatment of the alcoholic organic brain syndrome: Double-blind, placebo-controlled clinical, psychometric and electroencephalographic mapping studies with modafinil. Neuropsychobiology 1993;27:26-39.
45. Teitelman E. Off-label uses of modafinil. Am J Psychiatry 2001;158:1341.
46. Fleminger S, Greenwood RJ, Oliver DL. Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database Syst Rev 2003;(1):CD003299.
47. Feeney DM, Gonzalez A, Law WA. Amphetamine, haloperidol and experience interact to affect the rate of recovery after motor cortex injury. Science 1982;217:855-857.
48. Goldstein LB. Common drugs may influence motor recovery after stroke. Neurology 1995;45:865-872.
49. Schallert T, Hernandez T, Barth T. Recovery of function after brain damage: Severe and chronic disruption by diaze­pam. Brain Res 1986;379:104-111.
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Source: Pharmacological interventions for traumatic brain injury | BC Medical Journal

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[Poster] Effectiveness of Phenytoin and Levetiracetam for Seizure Prophylaxis Among a Traumatic Brain Injury Population: A Systematic Review

To examine the effectiveness of levetiracetam and phenytoin for seizure prophylaxis following brain injury.

Source: Effectiveness of Phenytoin and Levetiracetam for Seizure Prophylaxis Among a Traumatic Brain Injury Population: A Systematic Review – Archives of Physical Medicine and Rehabilitation

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[Abstract] Cannabis and other illicit drug use in epilepsy patients – Hamerle – 2013 – European Journal of Neurology.


Background and purpose

This study aimed to assess the prevalence of illicit drug use among epilepsy patients and its effects on the disease.


We systematically interviewed epilepsy outpatients at a tertiary epilepsy clinic. Predictors for active cannabis use were analysed with a logistic regression model.


Overall, 310 subjects were enrolled; 63 (20.3%) reported consuming cannabis after epilepsy was diagnosed, and 16 (5.2%) used other illicit drugs. Active cannabis use was predicted by sex (male) [odds ratio (OR) 5.342, 95% confidence interval (95% CI) 1.416–20.153] and age (OR 0.956, 95% CI 0.919–0.994). Cannabis consumption mostly did not affect epilepsy (84.1%). Seizure worsening was observed with frequent illicit (non-cannabis) drug use in 80% of cases.


Cannabis use does not seem to affect epilepsy; however, frequent use of other drugs increases seizure risk.

Source: Cannabis and other illicit drug use in epilepsy patients – Hamerle – 2013 – European Journal of Neurology – Wiley Online Library

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[ARTICLE] Fewer specialists support using medical marijuana and CBD in treating epilepsy patients compared with other medical professionals and patients: Result of Epilepsia’s survey – Full Text



From May 20 to September 1 2014, Epilepsia conducted an online survey seeking opinions about the use of medical marijuana and cannabidiol (CBD) for people with epilepsy. This study reports the findings of that poll.


The survey consisted of eight questions. Four questions asked if there were sufficient safety and efficacy data, whether responders would advise trying medical marijuana in cases of severe refractory epilepsy, and if pharmacologic grade compounds containing CBD should be available. Four questions addressed occupation, geographic region of residence, if responders had read the paper, and if they were International League Against Epilepsy/International Bureau for Epilepsy (ILAE/IBE) members.


Of 776 who started or completed the survey, 58% were patients from North America, and 22% were epileptologists and general neurologists from Europe and North America. A minority of epileptologists and general neurologists said that there were sufficient safety (34%) and efficacy (28%) data, and 48% would advise using medical marijuana in severe cases of epilepsy. By comparison, nearly all patients and the public said there were sufficient safety (96%) and efficacy (95%) data, and 98% would recommend medical marijuana in cases of severe epilepsy. General physicians, basic researchers, nurses, and allied health professions sided more with patients, saying that there were sufficient safety (70%) and efficacy (71%) data, and 83% would advise using marijuana in severe cases. A majority (78%) said there should be pharmacologic grade compounds containing CBD, and there were no differences between specialists, general medical personal, and patients and the public.


This survey indicates that there is a wide disparity in opinion on the use of medical marijuana and CBD in the treatment of people with epilepsy, which varied substantially, with fewer medical specialists supporting its use compared with general medical personal, and patients and the public.

Continue —> Fewer specialists support using medical marijuana and CBD in treating epilepsy patients compared with other medical professionals and patients: Result of Epilepsia’s survey – Mathern – 2014 – Epilepsia – Wiley Online Library

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[Research Reports] Pharmacotherapy for chronic cognitive impairment in traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of chronic disability. Worldwide, it is the leading cause of disability in the under 40s, resulting in severe disability in some 150 to 200 million people per annum. In addition to mood and behavioural problems, cognition-particularly memory, attention and executive function-are commonly impaired by TBI. Cognitive problems following TBI are one of the most important factors in determining people’s subjective well-being and their quality of life. Drugs are widely used in an attempt to improve cognitive functions. Whilst cholinergic agents in TBI have been reviewed, there has not yet been a systematic review or meta-analysis of the effect on chronic cognitive problems of all centrally acting pharmacological agents.
OBJECTIVES: To assess the effects of centrally acting pharmacological agents for treatment of chronic cognitive impairment subsequent to traumatic brain injury in adults.
SEARCH METHODS: We searched ALOIS-the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register-on 16 November 2013, 23 February 2013, 20 January 2014, and 30 December 2014 using the terms: traumatic OR TBI OR “brain injury” OR “brain injuries” OR TBIs OR “axonal injury” OR “axonal injuries”. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. Supplementary searches were also performed in MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CINAHL, LILACs,, the World Health Organization (WHO) Portal (ICTRP) and Web of Science with conference proceedings.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the effectiveness of any one centrally acting pharmacological agent that affects one or more of the main neurotransmitter systems in people with chronic traumatic brain injury; and there had to be a minimum of 12 months between the injury and entry into the trial.
DATA COLLECTION AND ANALYSIS: Two review authors examined titles and abstracts of citations obtained from the search. Relevant articles were retrieved for further assessment. A bibliographic search of relevant papers was conducted. We extracted data using a standardised tool, which included data on the incidence of adverse effects. Where necessary we requested additional unpublished data from study
authors. Risk of bias was assessed by a single author.
MAIN RESULTS: Only four studies met the criteria for inclusion, with a total of 274 participants. Four pharmacological agents were investigated: modafinil (51 participants); (-)-OSU6162, a monoamine stabiliser (12 participants of which six had a TBI); atomoxetine (60 participants); and rivastigmine (157 participants). A meta-analysis could not be performed due to the small number and heterogeneity of the studies.All studies examined cognitive performance, with the majority of the psychometric sub-tests showing no difference between treatment and placebo (n =
274, very low quality evidence). For (-)-OSU6162 modest superiority over placebo was demonstrated on three measures, but markedly inferior performance on another. Rivastigmine was better than placebo on one primary measure, and a single cognitive outcome in a secondary analysis of a subgroup with more severe memory impairment at baseline. The study of modafinil assessed clinical global improvement (n = 51, low quality evidence), and did not find any difference between treatment and placebo. Safety, as measured by adverse events, was reported by all studies (n = 274, very low quality evidence), with significantly
more nausea reported by participants who received rivastigmine compared to placebo. There were no other differences in safety between treatment and placebo. No studies reported any deaths.
AUTHORS’ CONCLUSIONS: There is insufficient evidence to determine whether pharmacological treatment is effective in chronic cognitive impairment in TBI. Whilst there is a positive finding for rivastigmine on one primary measure, all other primary measures were not better than placebo. The positive findings for (-)-OSU6162 are interpreted cautiously as the study was small (n = 6). For modafinil and atomoxetine no positive effects were found. All four drugs appear to be relatively well tolerated, although evidence is sparse.

Source: Traumatic Brain Injury Resource Guide – Research Reports – Pharmacotherapy for chronic cognitive impairment in traumatic brain injury

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[ARTICLE] Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence – Full Text HTML


Background: Several clinical studies have indicated that selective serotonin reuptake inhibitors (SSRIs) administered in patients after acute ischemic stroke can improve clinical recovery independently of depression. Due to small sample sizes and heterogeneous study designs interpretability was limited in these studies. The mechanisms of action whereby SSRI might improve recovery from acute ischemic stroke are not fully elucidated.

Methods: We searched MEDLINE using the PubMed interface to identify evidence of SSRI mediated improvement of recovery from acute ischemic stroke and reviewed the literature on the potential underlying mechanisms of action.

Results: Among identified clinical studies, a well-designed randomized, double-blind, and placebo-controlled study (FLAME – fluoxetine for motor recovery after acute ischemic stroke) demonstrated improved recovery of motor function in stroke patients receiving fluoxetine. The positive effects of SSRIs on stroke recovery were further supported by a meta-analysis of 52 trials in a total of 4060 participants published by the Cochrane collaboration. Based on animal models, the mechanisms whereby SSRIs might ameliorate functional and structural ischemic-brain damage were suggested to include stimulation of neurogenesis with migration of newly generated cells toward ischemic-brain regions, anti-inflammatory neuroprotection, improved regulation of cerebral blood flow, and modulation of the adrenergic neurohormonal system. However, to date, it remains speculative if and to what degree these mechanisms convert into humans and randomized controlled trials in large populations of stroke patients comparing different SSRIs are still lacking.

Conclusion: In addition to the need of comprehensive-clinical evidence, further elucidation of the beneficial mechanisms whereby SSRIs may improve structural and functional recovery from ischemic-brain damage is needed to form a basis for translation into clinical practice.

Continue —> Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence – Siepmann – 2015 – Brain and Behavior – Wiley Online Library


Possible mechanisms of action. The figure illustrates three possible mechanisms whereby SSRIs might improve structural-brain tissue recovery from ischemia: stimulation of neurogenesis in the subependymal zone and hippocampal dentate gyrus, inhibition of microglia- and neutrophile-induced inflammation mediated by cytotoxic inflammatory molecules, and improvement of cerebral vascular autoregulation (HO-1, heme oxygenase-1; VEGF, vascular endothelial growth factor).

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[ARTICLE] Pharmacological interventions other than for spasticity after stroke – Full Text HTML


This is the protocol for a review and there is no abstract. The objectives are as follows:


To determine if pharmacological interventions for spasticity are more effective than no intervention, normal practice or control at improving function following stroke.


To determine if pharmacological interventions for spasticity after stroke are more effective than no intervention, normal practice or control at:

  1. preventing secondary complications such as pain and contractures;
  2. decreasing spasticity at an impairment level.
  3. To determine if global antispasmodic interventions are more effective than local treatments at improving function after stroke.
  4. To determine if early administration of pharmacological interventions for spasticity (before six months) are more effective than late administration (after six months) of pharmacological intervention at improving function after stroke
  5. To determine the side effects of the use of pharmacological interventions against placebo
  6. To determine whether there is a difference between using pharmacological interventions for spasticity compared with no intervention, normal practice or control at improving function of the arm or leg following stroke.
    1. preventing secondary complications such as pain and contractures;
    2. decreasing spasticity at an impairment level.

Full Text HTML –>  Pharmacological interventions other than botulinum toxin for spasticity after stroke – Lindsay – 2013 – Cochrane Database of Systematic Reviews – Wiley Online Library.

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[ARTICLE] The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury – Full Text HTML


  • When administered acutely (within 12 hours after injury) low-dose methamphetamine significantly improves cognition and functional behavior.
  • The neuroprotective potential of methamphetamine is highly dose dependent.
  • Methamphetamine mediates dose dependent neuroprotection when administered within 12 h after severe TBI or stroke.


Methamphetamine is a psychostimulant that was initially synthesized in 1920. Since then it has been used to treat attention deficit hyperactive disorder (ADHD), obesity and narcolepsy. However, methamphetamine has also become a major drug of abuse worldwide. Under conditions of abuse, which involve the administration of high repetitive doses, methamphetamine can produce considerable neurotoxic effects. However, recent evidence from our laboratory indicates that low doses of methamphetamine can produce robust neuroprotection when administered within 12 h after severe traumatic brain injury (TBI) in rodents. Thus, it appears that methamphetamine under certain circumstances and correct dosing can produce a neuroprotective effect. This review addresses the neuroprotective potential of methamphetamine and focuses on the potential beneficial application for TBI.

Continue –>  The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury.

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[WEB SITE] Tranexamic Acid May Improve Traumatic Brain Injury Outcome

…Lead investigator in Houston, Dr. Bryan Cotton, is a professor at the Department of Surgery at the University of Texas Health Science Center (UTHealth) Medical School. He and his team will evaluate the potential benefits of administering TXA immediately in the event of a TBI, and whether it leads to improved mental recovery. Participating in this study are several Level 1 trauma care centers in the US, including Memorial Hermann-Texas Medical Center…

via Tranexamic Acid May Improve Traumatic Brain Injury Outcome.

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