Discuss the role and limitations of pharmacological intervention in the treatment of traumatic head injury
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Traumatic head injury or traumatic brain injury (TBI) nowadays is considered as a significant medical issue throughout the world and is the main reason behind the disability and death of young adults and as well as children also. Even survivors have to face challenges for the wide and the devastating effects of TBI. Those survivors most often are faced with agitation, weaken memory, anxiety as well as changes in behaviour that may reduce their quality of life. There are several pharmacological therapeutic agents are available such as anticonvulsants, psycho stimulants and antidepressants etc for the management of immediate as well as a long period outcome of neurocognitive, neurobehavioral and neuropsychiatric changes in case of TBI patients. (Bcmj.org, 2017)
Traumatic brain injury (TBI) can be designated as a complex form of head injury by the external force and may cause permanent or temporary impairment of functional, cognitive, physical and psychosocial in association with changed or declined state of awareness. In the US, near about 1.5-2 million people are affected by TBI in every year, among them, one-fourth people have an urgent need for hospitalization because severe TBI may cause the death of approximately 35%–40% patients. The direct and indirect evaluation cost of TBI estimates approximately 50-100 billion dollars annually in the US. Posttraumatic brain injury actually represents a combined effect of primary and secondary brain injury. (Beauchamp and Mutlak, 2017) The external mechanical force usually impacts promptly on skull and brain and leading to cause of primary brain injury, over the time secondary brain insult arises due to the occurrence of various biochemical and molecular path physiological events and that further may cause complexity like brain edema, neuroinflammation, and retardation in the normal neuronal death process.
Regulation related to Pharmacological interventions:
In present days, the survival rate of head-trauma patients with neurological impairments and TBI affected disabilities increase with the better understanding of altered complex cascades of molecular and cellular events that developed after TBI and with modern as well as most advanced therapeutic management. There are several potential medications have been introduced that may prevent the occurrence or decline the effects of secondary brain insult, also helps in rapid recovery by increasing functions of neurological events without affecting others. Recently, the TBI-related revised medical treatment guidelines or regulatory alert or The U.S. Food and Drug Administration (FDA) warning are published by National Guideline Clearinghouse (NGC), which are as follows-
Plan for the use of Pharmacological Intervention in the treatment of TBI:
The use of pharmacological interventions should be taken with great care and after discussing the pros and cons of the therapeutic medications like its adverse effects, ineffectiveness, overdose and several other details with the respective patient’s family members to avoid the further hazard in the treatment process.
Selection of target-based therapeutic agent is the most difficult decision that must be made after very precise and attentive analysis of the present disabilities and other associated factors like lesion nature and how much time passed after brain injury. (Bcmj.org, 2017)
The role of Psychostimulant drugs:
Attention deficit hyperactivity disorder (ADHD) is a condition that has almost similar symptoms and characterization to brain injury and also associated with aberrations of neurotransmitter can be treated with Psychostimulant drugs like methylphenidate. (Evans and Gualtieri, 1987)
This drug usually thought to bind with dopamine receptor, thus prevent the reuptake and then enhancing the extracellular level of dopamine, specifically in frontal cortex area (Challman and Lipsky, 2000). It may also enhance the level of serotonin and norepinephrine. Several studies have revealed that the administered dose should be 10-15 mg or 0.3 mg/kg, twice in a day. ((Kaelin, Cifu and Matthies, 1996, Speech et al., 1993, Plenger et al., 1996, Mooney and Haas, 1993)
According to study, methylphenidate is more beneficial for the treatment of chronic stage after TBI than the acute phase of TBI; as the patients with chronic phase shows improvements in alertness, workability whereas evidence in acute phase patients after the TBI shows the improvements in concentration, task performance on motor memory within the first month of administration, but improvements did not last for long term basis. (Whyte et al., 1997) some studies revealed that methylphenidate is more effective for the treatment management of seizures and agitation (Wroblewski et al., 1992, Evans, Gualtieri and Patterson, 1987), whereas other studies suggest no such benefit involves for neurobehavioral performance. (Forsyth and Jayamoni, 2003)
But, recent studies concluded that presently there is not enough evidence is present that can support the beneficial role of methylphenidate or other amphetamines which thought to facilitate recovery from traumatic head injury. (Siddall, 2003) But other studies also demonstrated the clinical trials of methylphenidate on patients surviving with TBI (acute and chronic) with specifically facing trouble for attention, cognitive processing, neurocognitive deficits, and speech.(Meythaler et al., 2001) Methylphenidate is consensus free stimulants for the treatment of motor activity and rapid in action with minor side effects and benefits for the treatment of chronic as well as the acute phase of traumatic head injury.
The role of Antidepressant drugs:
Post-TBI psychiatric events and other neurological deficits can be treated with antidepressants. The behavioural disorders in case of TBI patients in chronic and subacute phase can be managed with Selective serotonin reuptake inhibitors (SSRIs). Most studies revealed the fact that SSRIs are used for the improvements of neurocognitive, neurobehavioral and neuropsychiatric deficits, particularly depression, loss of memory, agitation etc.
A minimum of an 8-week duration of 100 mg average dose of Sertraline dose is required for the treatment of depression, agitation, psychomotor speed deficit; recent memory loss etc. (STENGLER-WENZKE and MÜLLER, 2002) In a similar way administration of fluoxetine 60 mg on a regular basis for about 3 months is useful for the treatment of TBI-related obsessive-compulsive disorder. (Muller et al., 1999) And also paroxetine or citalopram daily dose of 10-40 mg found to be beneficial to manage the pathological crying symptoms. (Teng et al., 2001) Other newly invented antidepressants like mirtazapine and venlafaxine can be effective on both norepinephrine and serotonin and are useful in the treatment of TBI. Bupropion enhances levels of dopamine and norepinephrine and 150 mg daily intake found to be useful for the treatment of restlessness. (Schneider, Jessie Drew-Cates, Tony, 1999)
The role of Antiparkinsonian drugs:
Bromocriptine, amantadine, levodopa in a combination with carbidopa all are known as antiparkinsonian drugs and possess a various target driven mechanism of action, also enhance the level of dopamine in the brain.
Usually, amantadine presynaptically acts for increasing the dopamine level or prevents its reuptake and also postsynaptically enhances the number or change the configuration of the dopamine receptor. (Kraus and Maki, 1997) It can serve as a NMDA receptor (non-competitive) and protect the excitotoxicity from the glutamate-mediated pathway in case of TBI. (Zafonte, Lexell, and Cullen, 2000) Bromocriptine is known as a dopamine receptor that affects D1 and D2 receptors.(22) The Levodopa and carbidopa both in a combination enhance the level of dopamine after decarboxylation and carbidopa also inhibit L-amino decarboxylase synthesis and by this way, levodopa makes its path towards the central nervous system. (Passler and Riggs, 2001)
Daily intake of amantadine about 100-300 mg found to be effective both in acute and chronic phases after traumatic head injury. Clinical demonstration study revealed that use of amantadine shows improvement in the case of motivation, attention, concentration, alertness and also effective to reduced processing time, agitation, fatigue, anxiety, and aggression issues.
Some cases with the use of bromocriptine (5-45 mg) daily and a combination of both bromocriptine (100mg) and ephedrine (100mg) also showed remarkable benefit in case of akinetic mutism. Bromocriptine in a combination with sensory stimulant also showed improvements in consciousness. (Karli et al., 1999)According to clinical study combined drug therapy like levodopa/carbidopa (25 mg/200 mg) thrice daily, amantadine/ bromocriptine (250/5mg) twice daily found to be effective for the improvement of neuropsychiatric deficits. (Wroblewski et al., 1997)
The role of Anticonvulsant drugs:
According to investigation use of Valproic acid (600-2250 mg) on daily basis showed positive result in neurocognitive actions also improve memory related troubles, reduces the neuropsychiatric and neurobehavioral related symptoms like aggressive or destructive behaviour, mania, depression, impulsiveness, restlessness etc (25-29) by increasing the control mechanism for GABA neurotransmitter, also facilitating stabilization of central nervous system.
The role of Other Drugs:
Modafinil is known for the treatment of post-TBI related symptoms like inattention, reduced urge for social activity, sleepiness etc. The mechanism of action involves the inhibition of GABA or enhancement of glutamate levels in the hypothalamus. (Ferraro, Antonelli and Tanganelli, 1999, Saletu et al., 1993). According to study intake of modafinil daily, at 100-400 mg plays an important role in the improvement of attention and memory related issues along with daytime sleepiness. (Teitelman, 1993, Fleminger, Greenwood and Oliver, 2003)
Beta blockers like propranolol and pindolol are found to be useful for the treatment of chronic and subacute phase of post-TBI neurobehavioral and neuropsychiatric symptoms such as agitation, aggression. (Feeney, Gonzalez and Law, 1982) Neuroleptics are also used to change the level of neurotransmitter in brain tissues.(Goldstein.1995, Schallert, Hernandez and Barth,1986). But some evidence does not suggest the use of agents like benzodiazepines, trazodone, neuroleptics, prazosin etc. as they may cause adverse reaction even after recovery due to their effect on neurotransmitters like GABA, dopamine etc.(37-39) Donepezil known as cholinesterase inhibitor which may effective for improvement of attention and memory at early phase but further use is strongly prohibited. (Walker et al., 2004, Levy et al., 2005)
Lastly, estrogens and progesterone or medroxyprogesterone known as antiandrogenic drugs are useful for the treatment of improper sexual behaviour in case of Traumatic head injury patients. (42)
Pharmacological interventions regarding the improvement of certain behavioural, cognitive and psychiatric symptoms associated with traumatic head injury patients are still under investigation.
The proper administration of therapeutic agents after determining neurological deficits, associated symptoms, timing and interaction nature with other agents either in the acute or chronic stage after traumatic head injury is considered as an important factor. For the establishment of guideline regarding treatment process of traumatic head injury patient’s careful documentation regarding medications and their side effects along with effectiveness to overcome disabilities and recovery are necessary for future study.
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