Neurostimulants Traumatic Brain Injury (TBI)

Severe Traumatic Brain Injury

Neurostimulants are used to treat TBI. They help to modulate the brain injury neurochemical changes associated with traumatic brain injury -or severe TBI. The goal is to help get the patient out of the intensive care unit and to regain neurologic functional recovery for the person with a traumatic brain injury (TBI). The off-label use of neurostimulants is very common and brain injury patients have a systematic review if they are using a neuro stimulant for their severe TBI.

Physical Medicine Long term disability

Neurostimulator vs Neurostimulant

The meaning NEUROSTIMULATOR is a device that provides electrical stimulation to nerves according to Merriam Webster’s dictionary. The idea is to interrupt the nerve signals for pain, but a neuro stimulant for brain injury or a severe traumatic brain injury does not have the same goal of interrupting nerve signals. The Neuro stimulant for traumatic brain injury patients, including intensive care unit patients, were not created specifically for traumatic brain injury patients.

Many companies will have a systematic review of each type of brain injury when they make an investment in neurostimulation. This can be anything from stroke, brain cancer, traumatic brain injury, etc… Such injuries are often severe and require long-term treatment and severe brain injury rehabilitation to help with the emotional regulation and the list of challenges on the road to functional recovery.

traumatic brain injury

But the neurostimulants that have been helpful for traumatic brain injury survivors have multiple neurostimulants uses. Often, they are developed for healthcare professionals to use to help patients with emotional regulation. They have been tested on patients in a persistent vegetative state, but the results require future studies.

Emotional regulation after a traumatic brain injury, or really any brain injury is often the placebo-controlled trial goal using physical medicine. Traumatic brain injury patients often are challenged when it comes to erratic emotions. It is not uncommon to try multiple neurostimulants because without trying multiple neurostimulants you won’t know which other neurostimulants may get the best functional outcome.

Various therapies are a helpful part of head trauma rehabilitation and prescribing multiple neurostimulants may be used in conjunction with traumatic brain injury rehabilitation protocols.

Acute Traumatic Brain Injury

Neurostimulants can be used to treat traumatic brain injuries, as well as a wide range of conditions, including acute brain injuries. They are used on an off-label basis, and there is no clear evidence that they work as advertised, but in the medical practice it is a smart move to wisely use drugs to discover if they may be effective for more than what they were created for.

Often, they are tested in a placebo controlled trial. The goal is to get functional outcomes and the tests are done in a systematic review process. One possible testing outcome is to use the Glasgow coma scale when appropriate.

In the following section, we will discuss some of the risks associated with neurostimulants use and discuss potential benefits.

Open access article distributed online provides feedback of how neuro stimulants may help TBI patients

If you are considering neurostimulants for post-traumatic brain injury (TBI) surgery, it is important that you discuss this with your surgeon. The risk of serious complications from a properly prescribed neuro stimulant is low compared to other medications used in the same way.

However, it is possible to have adverse effects from even small doses of neurostimulants such as levodopa or amphetamine. It may be difficult to make informed decisions about whether or not to use these medications if you do not discuss them with your surgeon before surgery.

Neurostimulants TBI Research and Clinical Studies

The endocannabinoid system (ECS) is involved in a variety of neurodegenerative disorders. The ECS has also been implicated in some therapeutic applications for the treatment of conditions such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis

traumatic brain injuries

The ECS has also been reported to play an important role in the prevention and treatment of traumatic brain injury.

In 2011, the first study sample/case reports properly cited was conducted on acute TBI using a novel non-steroidal anti-inflammatory agent (NSAID) called amantadine in mice. The results showed that amantadine produced significant improvements in motor function, memory function, and motor coordination [2]. Since then, several other studies have been conducted on animals with traumatic brain injury.

The long term effects of amantadine on the brain are unknown but there are reports that it can help restore cognitive abilities, improve motor functions and reduce depression in patients with TBI.

Neurostimulants TBI Safety and Adverse Effects

Neurostimulants are used off-label to treat traumatic brain injury (TBI). Although some of these drugs are not approved by the FDA for this use, they have been widely used in clinical practice. Though the therapeutic benefits of neurostimulants for TBI are promising, there is a significant risk of neuropsychiatric side effects with such use.


Research has shown that neurostimulants can increase a patient’s level of arousal and induce hyperarousal and hypervigilance.

The most common side effects include anxiety and psychosis, which can lead to serious problems when patients ingest potentially dangerous amounts of the drugs.

The FDA has issued a formal advisory on the safety and effectiveness of these drugs, which is currently available at

Neurostimulants TBI Mechanisms of Action

Neurostimulants are non-selective neuromodulators. They work by increasing the number of excitatory neurotransmitters (neurotransmitters that cause an increase in synaptic activity) and inhibitory neurotransmitters (neurotransmitters that decrease synaptic activity).

The various types of neurostimulants are:

• Dopamine agonists such as ropinirole (Requip), gabapentin (Neurontin) or pregabalin (Lyrica). These drugs normally act at GABAergic synapses.

• Norepinephrine agonists such as methylphenidate, butalbital and bupropion. These drugs normally act at dopaminergic synapses.

• Serotonin agonists such as sertraline and clomipramine. These drugs normally act at 5-HT2A/2C receptors.

Neurostimulants fall into two broad groups:  

The ‘core’ group, includes dopamine agonists, serotonin agonists and norepinephrine agonists, and the ‘synthetic’ group, which includes amphetamines/methamphetamines, cocaine/crack and MDMA/Ecstasy.

The following is a list of common neurostimulant used for TBI rehabilitation:  

• Ropinirole: a dopamine receptor antagonist with little activity in the mesolimbic dopamine pathway; may be more effective than placebo in maintaining function in patients with TBI
• GABAPENTIN: a GABA receptor antagonist that may be more effective than placebo in maintaining function in patients with TBI
• Pregabalin: an alpha 1-adrenergic receptor agonist that may be more effective than placebo in maintaining function in patients with TBI
• Methylphenidate: a noradrenergic receptor antagonist that may be more effective than placebo in maintaining function in patients with TBI

Special neurostimulants

In addition to these medications there are also special neurostimulants designed for specific indications:  Treatment of impulsivity: Abilify; Treatment of anxiety disorders: Abilify, Seroquel; Treatment of chronic pain: Botox®. These medications include medications used to treat Attention Deficit Hyperactivity Disorder (ADHD): Risperidone®. Other FDA approved medications include antidepressants like Zoloft®, Norco® , Celexa®, Paxil®, Prozac®, Lexap

Severe Brain Injury

Amantadine is an anticholinergic (antihistamine) used for behavioral disturbances in animals. It is a selective acetylcholine receptor antagonist with no known central nervous system (CNS) side effects.

It has been used in animal models of traumatic brain injury and can be used as a therapeutic agent in humans. Anecdotal clinical use of amantadine has demonstrated promising results and looks promising to the clinical setting.

About The Author

Tiffany Dyar

Tiffany Dyar is the former Executive Director for The Center for Health Innovation & Implementation Science, and the former Program Manager at Regenstrief Institute.Tiffany has co-authored several medical publications including The American Journal of Critical Care  Journal of General Internal Medicine Trials Journal  Best Practices in Mental Health  & The New England Journal of Medicine

Scroll to Top