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Does Amantadine Help Elderly Residents with Symptomless Dysphagia?
Dysphagia is prevalent in elderly patients who have experienced a stroke or those with certain neurological conditions, such as Parkinson’s disease. It can also occur as a consequence of physiologic changes associated with advancing age. In some individuals, dysphagia is symptomless. It can progress to silent aspiration and, ultimately, aspiration pneumonia (AP) in these patients, which is sometimes fatal. Silent aspiration is typically confirmed with a swallow study, and treatment generally involves imposing severe dietary restrictions that many patients associate with poorer quality of life. Studies have found that patients with dysphagia often have lower levels of dopamine and substance P, a neurotransmitter involved in swallowing and the cough reflex. The authors treated 12 nursing home patients with amantadine, a dopamine antagonist, in an effort to improve swallowing ability and decrease the incidence of aspiration and AP. This article reviews the etiology of dysphagia and silent aspiration and presents two cases from this small series. (Annals of Long-Term Care: Clinical Care and Aging. 2011;19[5]:37-40.)
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Physiological changes associated with aging or disease can impede a patient’s ability to swallow solids or liquids, a complication known as dysphagia. Dysphagia can occur at any of the three stages of deglutition: oral, pharyngeal, or esophageal. Patients with dysphagia are at risk of inadequate nutritional intake and predisposed to silent aspiration, in which food or liquids are inhaled into the lungs. This can lead to clinically significant aspiration pneumonia (AP), a common occurrence in older adults who have had a stroke or who have Parkinson’s disease or dementia, many of these patients reside in long-term care facilities.1
Stroke and Parkinson’s disease are associated with decreased dopamine metabolism and correspondingly decreased levels of the neurotransmitter substance P in the glossopharyngeal and sensory vagal nerves, which are active in swallowing and the cough reflex.2 This suggests that dopamine impairment is involved in the pathophysiology of dysphagia for some patients, a finding that prompted us to investigate whether amantadine, a dopamine agonist, could improve deglutition.
We used amantadine in 12 long-term care patients and discuss these results. We also review the cases of two patients with symptomless dysphagia treated with amantadine, including one with a history of stroke and the other with no evidence of prior stroke or Parkinson’s disease.
Case Report 1
An 83-year old black woman with a medical history of multinodular goiter, hypertension, and rheumatoid arthritis was admitted to the hospital for failure to thrive over the past year. Upon admission, her weight was 190 lb, which was 10 lb less than her baseline weight. She reported difficulty swallowing solids and liquids and described the onset of dysphagia as sudden.
The patient’s hypertension and rheumatoid arthritis were well controlled. A work up for stroke was negative, and thyroid function test results fell within normal limits. Ultrasonography of the thyroid showed a multinodular goiter with no evidence of esophageal compression. Magnetic resonance imaging (MRI) of the cervical spine revealed osteophytes that were possibly impinging on the esophagus. Results from aflexible nasolaryngoscopy and upper gastrointestinal endoscopy were normal. An acute abdominal radiograph series showed no evidence of intestinal obstruction or ileus. Dysphagia was confirmed with a modified barium swallow study (MBSS), which demonstrated slow initiation, throat clearing, and a weak cough response, as well as aspiration of pureed and thick liquids.
A percutaneous endoscopic gastrostomy (PEG) tube was placed at the hospital and tube feeds were initiated. The goal was for the patient to receive continuous enteral feeding at the rate of 70 mL per hour, which was achieved.
The patient was discharged to a skilled nursing facility, where she was found to have depression on admission. She began oral antidepressants, receiving citalopram 20 mg in the morning and mirtazapine 15 mg at night. To address the patient’s dysphagia, she was started on a rehabilitation regimen consisting of an oropharyngeal exercise program and neuromuscular electric stimulation. Two weeks after admission, she still had difficulty swallowing.
The patient and her family expressed frustration with her lack of improvement and our inability to determine the exact cause of the dysphagia. They accepted our offer to start the patient on a trial of amantadine.
The initial dose was 50 mg daily delivered via a PEG tube, which was increased to 100 mg daily after 1 week of treatment, during which time she started to be weaned off the tube feeds. After taking amantadine for 2 weeks, the patient asked to take food by mouth. We decided to conduct a bedside trial of pureed food, which the speech therapist also attended. During the test, no signs or symptoms of aspiration were observed and the tube feeds were stopped. After 6 weeks of amantadine treatment, the patient returned to her baseline weight of 200 lb, and amantadine was discontinued.
Twelve weeks after the patient was discharged from the nursing facility, her PEG tube was removed and she was followed in the outpatient clinic. Since then, her dysphagia has not returned and her weight remains stable.
Case Report 2
An 86-year-old white man had 6 hospital admissions in 6 months for failure to thrive and recurrent AP. He had experienced a stroke approximately 1 year earlier, and an MRI of his brain at the hospital showed subacute ischemia within the right hemisphere and the posterior frontal lobe, along with significant loss of cerebral volume due to multiple aneurysms and infarctions.
An MBSS was conducted with the assistance of a speech therapist, which revealed oropharyngeal dysphagia for solids and liquids. The patient’s cough response was delayed with liquids and immediate with solids, and swallowing was limited. He demonstrated a delay in swallow initiation, and during a trial of thin liquids, he aspirated twice. The speech therapist recommended a diet of thickened nectar. Despite diet modification and speech therapy, the patient continued to experience recurrent AP and was discharged to the nursing home for palliative care.
The patient’s medical history included hypertension, hyperthyroidism, and benign prostatic hypertrophy. Thirty years ago, he experienced a cerebrovascular accident secondary to aneurysmal rupture, which caused intracranial bleeding. He was left with residual right-sided hemiplegia, complicated by dysphagia and expressive aphasia.
During a physical examination conducted prior to admission to the nursing facility, the patient was noted to be severely debilitated with contractures involving the upper and lower extremities on his right side. In an interview, conducted as part of the initial history and physical, the patient stated, “Please change my diet or let me go.”
We provided a detailed explanation of the risks associated with resuming a normal diet to the patient and his family. The patient’s durable power of attorney decided to sign a diet waiver. The patient was subsequently started on oral amantadine at a dose of 50 mg daily for 1 week, after which the dose was increased to 100 mg daily. After 2 weeks of treatment with amantadine, his deglutition improved and we observed fewer secretions and decreased drooling of saliva. The patient did not exhibit any treatment-related adverse effects. After 6 weeks of amantadine, his weight increased by 6 lb. He continued to demonstrate improvement, and he even starting to use his computer. The patient was eventually discharged from hospice care and died 1 year later secondary to comorbid conditions.
Discussion
Brin and Younger reported that approximately 25% of hospitalized patients have difficulty swallowing,3 whereas Layne and associates determined that dysphagia is evident in 30% to 40% of nursing home patients.4 While dysphagia occurs in people of all ages, it is more common among elderly adults.
Advancing age produces physiologic changes associated with poorer deglutition. Two-thirds of older adults experience diminished masticatory muscle strength and changes in the tongue’s connective tissue that negatively affect swallowing in the oral phase. Other age-related changes associated with dysphagia include deterioration of the laryngo-upper esophageal sphincter contractile reflex and salivary gland function.5-8
Certain medical conditions, such as neurological disorders and stroke, contribute to an increased risk of dysphagia.9 Stroke can impair swallowing and coughing reflexes, and studies indicate that between 40% and 70% of elderly patients experience dysphagia after a stroke.1
Many stroke patients develop what is described as symptomless dysphagia, a complication that can lead to serious illness and mortality.10-12 The literature varies on the overall prevalence of symptomless dysphagia, but retrospective studies place its incidence at 25% to 30%.13,14 Patients with symptomatic and asymptomatic dysphagia have a higher rate of AP, which is a leading cause of mortality in patients who have suffered an ischemic stroke.12,15-17
Silent Aspiration
One complication of dysphagia is aspiration, defined as food, liquid, or gastric contents entering the trachea or lungs. If aspiration occurs without any readily observable indication, such as coughing or throat clearing, it is referred to as silent aspiration.1 Silent aspiration associated with symptomless dysphagia is a significant risk factor for AP.
Patients whose swallowing difficulties arise from weakness or incoordination of the pharyngeal muscles, or who have reduced laryngopharyngeal sensation, a defective cough reflex, or diminished local sensitivity, are predisposed to silent aspiration.18 Poor oral hygiene and comorbid conditions such as stroke, Parkinson’s disease, and dementia are associated with an increased risk of silent aspiration, but it has also been observed in patients who have no comorbidities.
Aspiration can occur during any of the three phases of deglutition. When food bolus is handled poorly during the oral phase, aspiration might take place before the pharyngeal phase of swallowing. Contributing factors include an increased sensory threshold for initiating deglutition, impaired pharyngeal peristalsis, and senescent changes to the upper esophageal sphincter opening.5-8
An indirect method for detecting silent aspiration is to use a pulse oximeter to record oxygen desaturation during swallowing.19 A greater than 2% drop in oxygen saturation while swallowing is suggestive of silent aspiration. It is important to note, however, that all pulse oximeters are labeled as accurate to within plus or minus 2% saturation. A videofluoroscopic study of the patient swallowing is considered the most effective means of assessing silent aspiration and its causes.20
Substance P
The neurotransmitter known as substance P is expressed in peripheral nerves, including the glossopharyngeal and sensory vagal nerves involved in swallowing and the cough reflex. It is also found centrally and peripherally in the oropharynx, along with receptors for dopamine, a neurotransmitter that interacts with substance P.21,22 Reduced levels of substance P and dopamine have been observed in patients with dysphagia secondary to stroke and in Parkinson’s disease. Parkinson’s disease causes dysfunction of the basal ganglia, a crucial region of the brain that works with the amygdala and insular cortex to control swallowing.2,10,21-24 Stroke can affect any of these cerebral areas.
In patients with bilateral basal ganglia infarcts, several studies have found reduced dopamine metabolism and subsequently lower levels of substance P in the peripheral fibers of the glossopharyngeal nerve and the superior laryngeal nerve (a branch of the vagus nerve), whereas others have found a higher rate of aspiration in patients with basal ganglia infarcts and correspondingly low expression of substance P.2,10,21-24 Although medications are available that increase dopamine or substance P levels, limited evidence supports this as the best approach to managing dysphagia.
Angiotensin-converting enzyme (ACE) inhibitors increase substance P levels and prevent degradation of substance P. They are considered more effective than angiotensin receptor blockers at boosting levels of substance P. Dopaminergic agents increase dopamine levels or increase substance P, which in turn improves the swallowing reflex. Studies have shown the dopaminergic drug levodopa to improve the swallowing reflex,24 and the antiparkinsonian agonists cabergoline and amantadine to reduce silent aspiration as efficiently as ACE inhibitors in elderly patients who have had a stroke.16
Amantadine potentiates dopamine neurons in substantia nigra to produce substance P, and it contributes to increased levels of substance P centrally and peripherally in the oropharynx.26-28 It may also increase the density of postsynaptic dopamine receptors.29 The release of dopamine further elevates the concentration of substance P, thereby activating the protective swallowing reflex.29 Other means by which amantadine might decrease aspiration is through improving alertness in patients who have had a brain injury, improving tone of the lower esophageal sphincter, and preventing influenza.
In a study by Nakagawa and associates26 to see whether amantadine could lower the risk of aspiration among elderly stroke patients, individuals treated with amantadine saw a 20% reduction in the risk of pneumonia. A randomized, controlled, clinical trial by Arai and colleagues16 also found a significant reduction in the risk of pneumonia among elderly patients given amantadine.
When using amantadine in elderly patients, it is important to consider the drug’s gastrointestinal and neurological adverse effects and its anticholinergic properties. Amantadine also has drug-to-drug interaction with some psychotropic medications. The drug is largely excreted by the kidneys; thus, clinicians should consider administering renal function tests prior to starting patients on amantadine.
Results of a Small Case Series
Based on data from the studies previously discussed, we decided to investigate the use of amantadine in a case series of 12 patients (age, 65-88 years) admitted to our long-term care facility. All patients had symptomless dysphagia and experienced silent aspiration or AP. In addition, 5 patients had a prior stroke, 4 had Parkinson’s disease, and 3 had swallowing problems related to aging.
Patients received a 50- to 100-mg daily dose of amantadine. After 2 to 4 weeks of use, 11 patients demonstrated a significant clinical improvement, including better swallowing ability, with decreased cough while eating and less drooling of saliva, and a gain in weight. During weeks 4 to 6 on amantadine, these patients were gradually able to tolerate food better without experiencing aspiration. Their improved ability to swallow contributed to substantial clinical benefit, including weight gain, fewer episodes of AP, and better quality of life as a result of removing dietary restrictions.
Only 1 patient failed to respond, showing no evidence of improvement in dysphagia symptoms. This patient had Parkinson’s disease and, despite amantadine treatment, gained no weight, continued to develop AP, and saw no improvement in quality of life.
Conclusion
Based on our small case series, it is possible that some elderly patients with symptomless dysphagia secondary to stroke, Parkinson’s disease, and age-related changes might benefit from treatment with amantadine. It is possible that ACE inhibitors might also improve some patient’s ability to swallow. In the absence of large, high-quality clinical trials with ACE inhibitors and amantadine in this patient population, we recommend initiating a 2-week therapeutic trial for select patients and carefully weighing the risks and benefits during this time. After 2 weeks of treatment, amantadine can be continued for patients who experience benefit and discontinued for those who are not helped.
Further studies are warranted to provide additional information on the effecacy and adverse effects of amantadine in elderly patients with symptomless dysphagia. Larger studies should seek to clarify the role of dopamine agonists such as amantadine and ACE inhibitors in elderly patients at risk for symptomless dysphagia.
The authors report no relevant financial relationships.
Dr. Gokula is assistant professor/program director, Department of Family Medicine, St Luke’s Hospital, University of Toledo Geriatrics Fellowship Program, Maumee, OH; Dr. Rubeen is research associate, Department of Family Medicine, University of Toledo, Toledo, OH; and Dr. Thotakura is research associate, Department of Family Medicine, University of Toledo, Toledo, OH.
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