Treatment of Psychiatric Symptoms in Alzheimer's Disease
The principal treatable neuropsychiatric disturbances in Alzheimer's Disease (AD) are:
Patients with AD may respond at least somewhat to antipsychotics, antidepressants, certain anticonvulsants, and other psychopharmacological (medicines for the treatment of psychiatric disturbances) agents, although there are no medicines specifically approved by the FDA for treating psychiatric symptoms in AD. The core medication treatments for AD -- pro-cholinergic drugs such as Aricept (donepezil), Exelon (rivastigmine), or Razadyne (galantamine), and anti-glutamate drugs such as Namenda -- are sometimes helpful in managing associated psychiatric symptoms in AD. Target symptoms should be clearly specified and documented and the treatment response should be evaluated regularly.
Agitation occurs in as many as 70% of patient with AD and is more common as the disease progresses. Classes of agents used to treat agitation include antipsychotics, mood-stabilizing anticonvulsants, trazodone, anxiolytics, the selective serotonin reuptake inhibitor (SSRI) citalopram, and beta-blockers. Available evidence suggests that antipsychotics, trazodone, or anticonvulsants have the greatest effectiveness in reducing agitation, but their impact is usually only modest. Atypical antipsychotic agents such as clozapine, risperidone, olanzapine, quetiapine, and ziprasidone appear to have advantages over the older antipsychotic agents based on their side effect profiles and the patients' ability to tolerate them. However, it is important to be aware that no antipsychotic drug is FDA-approved for treatment of dementia-related psychosis, and all carry an increased risk for death in this population.
Psychosis is common in AD, with a frequency of about 50% over the lifetime of an AD patient. Atypical antipsychotics have not been conclusively proven to help psychotic symptoms in this population and must be balanced against their risks, While some experts discourage the use of antipsychotics in patients with AD, others recommend their gentle use at low doses with careful monitoring of cardiac and other safety concerns. Sedation (dullness, calmness) is the most common side effect noted in patients receiving antipsychotics.
Depressive symptoms are frequent in AD and occur in as many as 50% of patients. Major depression is more unusual. The treatment of depressive symptoms commonly consists of SSRIs such as sertraline, citalopram, or fluoxetine. Full doses of the SSRIs are generally tolerated in the elderly, which is unlike most other psychotropic agents wherein lower doses are typically used. Alternatively, tricyclic antidepressants with few anticholinergic (dry mouth, constipation, memory problems) side effects, such as nortriptyline, or combined noaradrenergic and serotonergic reuptake inhibitors, such as venlafaxine, have been used.
Anxiety is a common symptom in AD, affecting 40% to 50% of patients at some point in the course of the illness. Most patients do not require medicines for the treatment of their anxiety. For those requiring medicines, benzodiazepines are best avoided because of their potential adverse effects on the thinking process. Nonbenzodiazepine anxiolytics, such as buspirone, trazodone, or SSRIs, are preferred. Behavioral strategies (for example, reassurance, reorienting, relaxation techniques) are also often favored over pharmacologic approaches.
Difficulty sleeping (insomnia) occurs in many patients with AD at some point in the course of their disease. Agents that are useful in treating insomnia in AD patients include nonbenzodiazepine sedative hypnotics, such as zolpidem or zaleplon, or sedating antidepressants, such as trazodone or mirtazapine. Other ways of improving sleep include exposure to sunlight, taking daytime walks, avoiding daytime naps, adequate treatment of pain, and limiting nighttime beverages.