By Mark D. Coggins, PharmD, CGP, FASCP
Vol. 5 No. 1 P. 32
Dementia describes a group of symptoms resulting in a gradual and progressive decline in memory, thinking, and reasoning abilities. While most dementias are progressive with no cure, approximately 20% are reversible. Healthcare professionals should closely evaluate patients with cognitive decline for possible underlying treatable conditions.
Medication-induced dementia is the most common cause of reversible dementia. Elders are especially vulnerable due to concomitant illnesses, reduced renal and liver function, and the simultaneous use of multiple medications.1
Other common reversible causes include depression, infection, high fever, vitamin deficiencies, poor nutrition, hypercalcemia, brain tumors, thyroid disorders, and hypoxia due to lung and heart diseases.
Alzheimer’s disease (AD) is the most common type of irreversible dementia. Other irreversible types include vascular or multi-infarct dementia, dementia with Lewy bodies (DLB), frontotemporal dementias (Pick’s disease), and Parkinson’s dementia (PD). Autopsy studies have shown that most dementia patients had brain abnormalities consistent with more than one dementia type.
In addition to progressive cognitive loss, almost all AD patients develop personality and significant behavioral changes. Mood disorders such as depression; nonpsychotic behaviors such as restlessness, wandering, and aggression; or psychotic symptoms, including hallucinations and delusions, often occur with severe disruptive behaviors, leading to 50% of nursing home admissions, according to the American Academy of Family Physicians.
Healthcare professionals should consider behaviors as a means of patient communication as AD patients lose their ability to adequately make their needs known. Agitation may be a result of underlying precipitating causes such as hunger, thirst, pain, or infection. Be aware that medication changes or poor hearing can increase confusion. Vision issues can contribute to visual hallucinations or increase a patient’s feeling of vulnerability or fear.
The failure to identify causes of these behaviors may leave a patient in distress and often results in the unnecessary use of behavior management medications. These may do little more than cause sedation and can lead to further cognitive decline, reduced patient activity, worsening incontinence, and falls, and make it more difficult for caregivers to provide assistance.
In cases where the behavior or psychiatric symptoms are severe, distressing, or may lead to harm, it may be necessary to prescribe medications.
Antipsychotic Use and Associated Risks
Antipsychotic use in dementia patients continues to be widespread despite clear and substantial risks to patient health.
All antipsychotic medications include FDA black box warnings due to the increased risk of death when used in dementia-related psychosis. Additional concerns include negative metabolic effects, weight gain, type 2 diabetes, dyslipidemia, and increased risk of stroke. Antipsychotics are also linked to a worsening decline in cognition consistent with one year’s deterioration compared with placebo.
Antipsychotics in AD patients should be reserved for behaviors that are harmful or when distressing psychotic features exist. They should be given short-term and at the lowest possible dose with frequent evaluation for discontinuation, according to the 2001 report “Psychotropic Drug Use in Nursing Homes” by the Office of Inspector General.
The widespread use of atypical antipsychotics despite the risks highlights the need for alternative behavior management medications and strategies.
Medication management in dementia patients can be complex. Unfortunately, no silver bullet exists for prescribers to call on to address dementia-related behaviors. Successful behavior management most often involves a combination of nonpharmacological approaches tailored to meet a patient’s needs in addition to one or more of the currently available medications, which often have limited supporting evidence in their effectiveness on behaviors.
Pain Treatment Can Influence Behaviors
Pain can diminish cognitive function, reduce patients’ ability to perform activities of daily living, adversely affect mood, and reduce quality of life.
In a 2010 study conducted at a Golden LivingCenter in Hendersonville, North Carolina,2 researchers found that increased pain management focus in nursing home patients with dementia helped reduce episodic behaviors. A certified geriatric pharmacist (CGP) provided education on pain assessment and treatment options to all nursing home staff and direct care assistants.
The CGP evaluated medical records of patients with such behaviors to determine whether common conditions known to cause pain, such as osteoarthritis, wounds, and neuropathy, were being treated. Recommendations based on the American Medical Directors Association pain management guidelines, including acetaminophen and other medications, were discussed with each patient’s physician, and appropriate medication changes were implemented. Following the treatment modification, the patients’ behaviors were tracked and were noted as significantly reduced, and nurses and nursing assistants noted that patients had become less resistant to care.
Additional follow-up discussions occurred between the nursing home interdisciplinary team and the CGP. As patient behaviors improved, the interdisciplinary team worked with prescribers to significantly reduce the number of antipsychotic, anxiolytic medications (benzodiazepines) and sedative/hypnotics being taken by these patients.2
Nursing home patients in Norway and England with moderate to severe dementia experiencing agitated behaviors had acetaminophen added to their existing pain orders or, if acetaminophen was already ordered, low doses of morphine, or they were given antiepileptic medications for neuropathic pain. Patients receiving more aggressive pain management had a significant reduction in undesirable behaviors. Following eight weeks of therapy, pain treatment added to the intervention group was gradually reduced. Follow-up four weeks later showed the recurrence of the behavior symptoms and further demonstrated the effectiveness of pain management in reducing negative behaviors.3
Medications commonly given to slow the progression of cognitive loss in dementia have shown modest benefit in controlling behaviors.
In several studies, acetylcholinesterase inhibitors (AchEIs), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyme) demonstrated some success in reducing dementia behavioral symptoms, including apathy, anxiety, delusions, and hallucinations. These medications appear to be effective in treating psychotic symptoms in patients with DLBT and PD.
Memantine (Namenda), an NMDA receptor antagonist used alone and with AchEIs, has shown moderate improvements in behavioral symptoms, including agitation, aggression, irritability, lability, and delusions. Additional benefits have been seen when using memantine together with AchEIs.4
Researchers have reviewed the evidence for the effectiveness and safety of antidepressants for dementia-related agitation and psychosis. While larger well-controlled studies are needed, many existing studies have provided hope that antidepressants, especially those known as selective serotonin reuptake inhibitors (SSRIs), have safe and tolerable side effect profiles and can be effectively used to help dementia-related behaviors in some patients.
Most of the studies involved SSRIs such as citalopram (Celexa) or sertraline (Zoloft). Improvements in depression, emotionality, anxiety, agitation, and social interaction have been seen when comparing citalopram with placebo.
In a study at the University of Pittsburgh Medical Center conducted with patients hospitalized with psychiatric disturbances related to dementia, patients receiving citalopram experienced similar results, or a 32% reduction in relieving hallucinations, delusions, and suspicious thoughts while those in the atypical antipsychotic risperidone (Risperadal) group had a 35% reduction. However, the patients receiving citalopram experienced a 4% reduction in side effects compared with a 19% increase in side effects in patients receiving risperidone.5
Many antidepressants have been shown to have favorable effects on anxiety, sleep disturbance, and agitated behaviors. Practical suggestions on ways to implement the use of antidepressants for behaviors may include selecting an agent based on the known beneficial effects and the specific behavioral symptoms exhibited.
SSRIs such as escitalopram (Lexapro) and sertraline have indications to treat anxiety. Because anxiety and agitation are often closely related, a reasonable selection of one of these antidepressants may be made for those dementia patients exhibiting signs and symptoms of depression with anxious agitated behaviors.
Prescribers may choose to start antidepressant medications such as SSRIs while slowly reducing or eliminating the use of higher risk medications, such as antipsychotics and benzodiazepines that are often used for anxiety. This can have further benefits for the patient since these medications are known to increase confusion and fall risk.
Depression is known to affect sleep in many patients with and without dementia. Patients receive benzodiazepines or hypnotic medications such as zolpidem (Ambien) for sleep, which has been linked to early morning falls. Physicians may choose to utilize the antidepressant mirtazepine (Remeron) at a dose of 30 mg for which there are studies showing improved sleep continuity long term.
Patients with dementia and diabetic neuropathy who exhibit undesirable behaviors may be experiencing pain. Consideration for this type of patient may be given to duloxetine (Cymbalta), an antidepressant known to help neuropathic pain and depression.
Pharmacological choices with FDA-approved indications and clear evidence in targeting behaviors in dementia are limited. However, improved nonpharmacological interventions, in addition to focused patient individualized prescribing targeting common underlying causes of behaviors seen in dementia patients, may allow for improved behavior symptom control with less risk than is currently seen today utilizing atypical antipsychotic medications.
— Mark D. Coggins, PharmD, CGP, FASCP, is the national director of clinical pharmacy services for more than 300 skilled nursing homes operated by Golden Living. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.
1. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289(9);1107-1116.
2. Coggins M, Evans MP, Bruce C. Effect of an interdisciplinary team approach to psychotropic drug reduction and elimination on quality measures and other clinical outcomes in skilled nursing facilities (SNFs): the Medication Evaluation Trial (MET trial). JAMDA. 2010;11(3):B9.
3. Husebo BS, Ballard C, Sandvik R, Bjarte Nilsen O, Aarsland D. Efficacy in treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomized clinical trial. BMJ. 2011;343:d4065.
4. Gauthier S, Wirth Y, Möbius HJ. Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the neuropsychiatric inventory (NPI) data of two randomized, controlled studies. Int J Geriatr Psychiatry. 2005;20(5):459-464.
5. Pollock BG, Mulsant BH, Rosen J, et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry. 2007;15(11):942-952.