Pharmacological Treatment of the Behavioral and Psychological Symptoms of Dementia

General Principles of Pharmacotherapy for the Behavioral and Psychological Symptoms of Dementia

• Accurately diagnose the underlying dementia. Treatment of behavioral and psychological symptoms of dementia will vary depending upon the underlying dementing disorder. For example, as we saw in Chapter 8 , although patients with dementia with Lewy bodies experience visual hallucinations, one must be very cautious in treating them because many antipsychotic drugs exacerbate their parkinsonian symptoms. Knowing that the patient has dementia with Lewy bodies will lead to the use of donepezil (Aricept) (or another cholinesterase inhibitor) as first-line therapy, a selective serotonin reuptake inhibitors (SSRI) such as sertraline (Zoloft) as second-line therapy, quetiapine (Seroquel) as third-line therapy, and risperidone (Risperdal) as fourth-line therapy, because donepezil and sertraline should not exacerbate parkinsonism at all, and quetiapine is less likely to exacerbate parkinsonism than risperidone.

• Identify and measure specific target symptoms. The clinician and caregiver should identify specific symptoms and behaviors that they wish to reduce, such as depression, wandering, or aggression. Each symptom should be measured at baseline such that, when a treatment is prescribed, the treatment effect on that symptom can be quantified. One common way to measure these symptoms and behaviors is to count how many times specific events occur in a period of time. (For example, the patient attempted to wander out of the house six times over a two-week period, or ask the caregiver if this is happening multiple times a day, once a day, several times a week, once a week, or once a month.)

• Start low, go slow—but go. Older adults are often more sensitive to medications. As such, doses in older individuals should start at one-third to one-half the standard adult dose. Titrations should be slower than in younger adults. Importantly, however, the drugs should be titrated until the desired response is achieved or until intolerable side effects emerge. We have too often seen patients treated for long periods on sub-therapeutic doses of drugs that are not having the desired effect. In many cases, when the doses were increased to therapeutic levels, the patients did better.

• Instruct the caregiver and patient both verbally and in writing. We have been surprised how often we will have a conversation with a patient and caregiver regarding medications only to realize they misunderstood what we said when we revisit the topic later. Because of the frequency of misunderstanding, we now provide information regarding medications both verbally and in clear, written directions. These instructions include how and when to take the medication, what side effects may occur and how to manage them, and what to do if they run out of medication. (See Box 19.4 for example.)

• Remove unneeded medications. It is both essential and difficult to obtain an accurate list of medications in our patients with dementia. In an informal survey that we completed several years ago, we found that our average patient reported taking eight medications—and some more than 20! In many cases neither the patients nor their caregivers knew who prescribed a number of their medications or what they were for. The typical scenario was that multiple providers added medications, but medications were rarely removed. A number of the commonly prescribed medications have potential cognitive side effects or drug interactions, including anticholinergic medications, antihistamines, and others. (See Box 17.1 , Box 17.2 .) We often begin by working with the patient’s primary care provider to try to simplify their medication regime.

• Change only one medication at a time. This very obvious point is often overlooked and it cannot be overstated. If more than one medication is changed at once it is generally impossible to determine the cause of either beneficial or detrimental cognitive effects. We therefore recommend changing only one medication at a time.

Pharmacotherapy for Depression

There are few things in our society today that are as depressing and anxiety provoking as realizing that one has Alzheimer’s disease and is going to literally “lose one’s mind.” Although it rarely meets the diagnostic criteria for major depression, a significant degree of depression often occurs in patients before, during, and throughout the course of Alzheimer’s disease, occurring in about half of patients ( ). Although treatment of depression in the demented patient will not resolve the cognitive deficits, successful treatment will help the mood of the patient and in doing so will improve the patient’s cognition, daily function, and overall well-being ( ).

Some general guidelines for managing depression pharmacologically:

• SSRIs are generally first-line therapy. (See Box 27.1 .)

  Box 27.1

  Use of Selective Serotonin Reuptake Inhibitors in Dementia

  • Selective serotonin reuptake inhibitors (SSRIs) are generally well tolerated in patients with cognitive impairment and dementia.

  • SSRIs are only minimally anticholinergic, are relatively non-sedating, and are therefore unlikely to worsen cognition.

  • Several SSRIs (including sertraline [Zoloft] and escitalopram [Lexapro]) are anxiolytics as well as antidepressants.

  • We generally use a low dose of:

    • Sertraline (Zoloft) target 75–150 mg QD; general range for dementia 50–200 mg

    • Escitalopram (Lexapro) target 10 mg QD; general range for dementia 5–10 mg.

    • Because of its cardiac effects on the QTc interval, citalopram (Celexa) is a second line drug to be used if sertraline and escitalopram are unsuccessful. Target 20 mg QD; general range for dementia 10–20 mg.

  • If one SSRI is not effective, others may be.

  • Main side effects: gastrointestinal upset and sexual dysfunction.

  • Note that paroxetine (Paxil) may be problematic in the elderly owing to the common side effect of hyponatremia, the rapid onset of withdrawal symptoms if a dose is forgotten, and its high anticholinergic burden compared with other SSRIs.

• Other antidepressant classes that may be beneficial for depression:

  • Bupropion (Wellbutrin) has activating properties and can also be helpful when apathy is present; may lower the seizure threshold, particularly in doses above 300 mg per day.

  • Serotonin–norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor), are efficacious in some patients.

• Antidepressants to avoid include:

  • Tricyclic antidepressants because of anticholinergic effects

  • Mirtazapine (Remeron) because of anticholinergic effects

  • Monoamine oxidase inhibitors (MAOs) because of the likelihood of dietary indiscretions in the cognitively impaired patient.