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Article Excerpt
Abstract: Methylphenidate (Ritalin) is a commonly used central nervous stimulant. It has been used in various neurological conditions, including attention deficit disorder, depression, and narcolepsy. Methylphenidate has been advocated in patients with traumatic brain injury and stroke for a variety of cognitive, attention, and behavioral problems. It also has been shown to speed recovery from post-stroke depression so that patients can participate more fully in rehabilitation programs. Research suggests that it also may have a role in augmenting activity of injured neuronal tissue in the comatose patient, thus facilitating a return to consciousness. The neuroscience nurse plays an important role in monitoring response to Ritalin, including identifying its side effects. A review of the limited studies on the use of Ritalin, its mechanisms of action, dosing, and weaning provide a current understanding of this adjunctive agent's role in treatment for the neurological population.
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Psychostimulants such as amphetamine, dextroamphetamine (DEA), nortriptyline, and methylphenidate have been used to enhance cognition and memory, modulate behavior, and arouse the neurological population for many years. These drugs exercise a positive effect on memory and attention and control behavioral disturbances such as hyperactivity, impulsivity, and emotional lability (Challman & Lipsky, 2000). Animal research has indicated that psychostimulants can influence recovery when given at early or later time points after brain injury (Walker-Batson, Smith, Curtis, Unwin, & Greenlee, 1995). A single dose of DEA was reported to produce an enduring acceleration of motor recovery after experimental lesions in the rat (Feeney, Gonzales, & Law, 1982). Intermittent dosing (every fourth day) also helped recovery in the cat (Hovda & Feeney, 1984). A recent study showed that water maze performance was enhanced after brain-injured rats received methylphenidate (Kline, Yan, Bao, Marion, & Dixon, 2000). Findings suggest that these drugs, which enhance catecholamine neurotransmission, might be a useful adjunct in some neurobehavioral sequelae following head injury in humans (Kline et al.).
Although researchers have suggested the use of various drugs in behavioral recovery for humans, evidence for its clinical application is limited (Walker-Batson et al., 1995). Methylphenidate (Ritalin) is commonly prescribed, specifically for stroke and brain injury patients, in the neuroscience setting. However, its mode of action in humans is not completely understood; it presumably modulates the neurotransmitters dopamine, serotonin, and norepinephrine (Kimko, Cross, & Abernathy, 1999). This article discusses the clinical usefulness of Ritalin in the neurologic patient population and reviews pharmacokinetics and clinical studies from 1984 to 2000.
Pharmacokinetics and Side Effects of Ritalin
Ritalin is a mild central nervous system stimulant whose mode of action is not completely understood (Kimko et al., 1999). It causes a dose-dependent change in behavior very similar to that of amphetamine. Amphetamine is thought to increase extracellular serotonin and dopamine in the caudate putamen and norepinephrine in the hippocampus, which in turn stimulates other circuits in the brainstem and cortex. Ritalin, in comparison, is thought to cause a smaller increase in norepinephrine, has no effect on serotonin, and exerts many of its effects through dopamine uptake blockade instead of a release of dopamine (Kuczenski & Segal, 1997). One recent study suggested that Ritalin enhanced working memory by modulating the frontal and posterior parietal regions in the human brain (Mehta et al., 2000).
Ritalin is a short-acting stimulant with a 1-4 hour duration of action and a half-life of 2-3 hours. However, sustained-release formulations are now available. Because of individual variability in the dose-response relationship, dosage must be divided and titrated up for optimal effect and to avoid toxicity (Stein et al., 1996; Volkow et al., 1998). Ritalin is absorbed well from the gastrointestinal tract and easily passes to the brain. It has mild side effects as compared to amphetamine, with an onset of action of 24-48 hours as compared to 1-2 weeks for antidepressants such as nortriptyline (Kimko et al., 1999).
Adverse effects of Ritalin are related to sympathetic nervous system stimulation, especially with long-term use. These effects include nervousness, insomnia, decreased appetite, nausea and vomiting, dizziness, drowsiness, blurred vision, increased blood pressure and pulse, and rash, pruritis, and fever. Symptoms of overdose include increased agitation, tremors, muscle twitching, confusion, hallucinations, sweating, hypertension, and cardiac arrhythmias (Long, 1999).
Potential adverse effects of Ritalin are of specific concern in patients with neurological injury. An incident of stroke due to cerebral arteritis caused by Ritalin use in an 8-year-old boy (Schteinschnaider et al., 2000) was recently reported. Wang et al. (1994) demonstrated that Ritalin decreased cerebral blood flow 5-10 minutes after its administration, warning that Ritalin should be used with caution when chronically prescribing the drug for patients with cerebrovascular compromise. Clinical evidence has shown that Ritalin may lower the seizure threshold. Hence, clinicians are reluctant to use Ritalin in the brain-injured patient with seizures. However, Wroblewski, Leary, Phelan, Whyte, and Manning (1992) concluded that Ritalin could be used safely in 26 brain-injured patients with active seizure disorders and actually was associated with a trend toward a reduction rather than an increase in seizure frequency. Finally, there is a potential for abuse with any psychostimulant. Deaths have been reported from both parenteral and intranasal abuse of Ritalin (Masello & Carpenter, 1999).
Clinical Uses
Attention-Deficit/Hyperactivity Disorder and Narcolepsy
Methylphenidate is a commonly used medication in the United States. The Food and Drug Administration (FDA) has approved its use for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. It is used with other remedial measures (e.g., psychological, educational, social) for a stabilizing effect in children with distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. In narcolepsy, it improves the signs and symptoms of hypersomnia and hypoarousal (Kimko et al., 1999).
Depression
Depression in the hospitalized patient who is elderly has an effect on several outcome measures, including prolonged recovery from medical illness, decreased motivation toward recovery, and noncompliance and decreased participation with medical therapy. Even though Ritalin is not FDA approved for treating depression, two early studies found the drug to be a safe and effective treatment of depression in the medically ill elderly (Koenig, Shelp, Goli, Cohen, & Blazer, 1989; Morris, Robinson, Andrzejewski, Samuels, & Price, 1993). Ritalin has an advantage over antidepressants such as nortriptyline because of its quick observable response and fewer side effects. Based on clinical data, the use of Ritalin in severe depression is cautioned, however, because it may exacerbate behavior disturbance and thought disorder symptoms. Also, the use of Ritalin with tricyclic antidepressants (TCAs) may increase side effects of these drugs (Emptage & Semla, 1996).
Use in the Neurological Patient Population
Ritalin has been used for patients with traumatic brain injury, post-stroke depression and recovery, the neurobehavioral deficits caused by brain tumors, and coma (Challman & Lipsky, 2000). These are all non-FDA-approved uses. There are limited studies involving the use of psychostimulants in the neurological patient. The current literature, which primarily consists of uncontrolled studies, dates back to 1984 and suggests a role for the use of Ritalin (Kraus, 1995).
Brain Injury
The cognitive and behavioral disturbances seen after head injury in both children and adults have been well documented in the clinical literature (Levin, Benton, & Grossman, 1982). Cognitive functions particularly vulnerable to head injury are memory and attentional and intellectual skills. It is common for patients with moderate to severe head injury to display behavioral disturbances, such as impulsivity and hyperactivity, after injury, and then to be treated with psychiatric medications such as antiepileptic drugs, neuroleptics, TCAs, and lithium to control neurobehavioral sequalae. However, these drugs can have an adverse effect on cognition, memory, and attention by blocking re-uptake of norepinephrine and serotonin (Evans et al., 1987).
Thus, attention has...
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