(AAN) updated treatment guidelines on the use of amantadine for patients with prolonged DoC, recommending the use of amantadine (100–200 mg bid) for adults with DoC 4–16 weeks post injury to support early functional recovery and reduce disability. Neuroplasticity and overall functional recovery in patients with brain injury In various studies, amantadine and memantine have been shown to accelerate the rate of recovery from a brain injury. The time-limited window following a brain injury is characterized by neuroplasticity, or the capacity of neurons in the brain to adapt and compensate after injury. Thus, physiatrists will often start patients on amantadine as soon as impairments are recognized. There are also case reports showing improved functional recovery with amantadine treatment occurring years after the initial brain injury. There is insufficient evidence to determine if the functional gains are a result of effects through the dopamine or norepinephrine pathways. Some patients may benefit from direct dopamine stimulation with amantadine, while others may benefit more from other stimulants that act more on the norepinephrine pathway, such as methylphenidate. It is unclear if treatment with amantadine improves long-term outcomes or simply accelerates recovery. Nonetheless, amantadine-induced acceleration of recovery reduces the burden of disability, lessens health care costs, and minimizes psychosocial stressors in patients. Attention deficit hyperactivity disorder A 2010 randomized clinical trial showed similar improvements in ADHD symptoms in children treated with amantadine as in those treated with methylphenidate, with less frequent side effects. A 2021 retrospective study showed that amantadine may serve as an effective adjunct to stimulants for ADHD–related symptoms and appears to be a safer alternative to second- or third-generation antipsychotics. Adverse effects Amantadine is generally well tolerated and has a mild side-effect profile. Neurological Side effects include drowsiness (especially while driving), lightheadedness, falls, and dizziness. Patients on amantadine should avoid combination with other central nervous system (CNS) depressing agents, such as alcohol. Excessive alcohol usage may increase the potential for CNS effects such as dizziness, confusion, and light headedness. Rare severe adverse effects include neuroleptic malignant syndrome, depression, convulsions, psychosis, and suicidal ideation. It has also been associated with disinhibited actions (gambling, sexual activity, spending, other addictions) and diminished control over compulsions. Cardiovascular Amantadine may cause orthostatic hypotension, syncope, and peripheral edema. Gastrointestinal Amantadine has also been associated with dry mouth and constipation. Skin Rare cases of skin rashes, such as Stevens–Johnson syndrome and livedo reticularis have also been reported in