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Review ArticleClinical Review

Guidelines for the Management of Cognitive and Behavioral Problems in Dementia

Carl H. Sadowsky and James E. Galvin
The Journal of the American Board of Family Medicine May 2012, 25 (3) 350-366; DOI: https://doi.org/10.3122/jabfm.2012.03.100183
Carl H. Sadowsky
MD
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James E. Galvin
MD, MPH
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    Figure 1.

    Treatment and management of Alzheimer disease. *Memory complaint may be raised by family or caregiver. All patients aged ≥75 years should be screened regardless of clinical presentation. †Cholinesterase inhibitors (ChEIs) are included for mild to moderate Alzheimer disease, excluding donepezil, which is indicated for mild, moderate, and severe Alzheimer disease. ‡Possible causes include medical comorbidities, the effects of other drugs, behavioral disturbances, or delirium. §Memantine is indicated for the treatment of moderate to severe Alzheimer disease. (This treatment algorithm is derived from recommendations published in Ref. 56. Reproduced with permission from RG Stefanacci. Reinforcing the value of combination therapy to treat moderate to severe alzheimer's disease. Phys Week 2009;26(9). © 2009 Physician's Weekly, LLC.)

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    Table 1. Cholinesterase Inhibitors and Memantine for the Treatment of Cognitive Deficits in Patients with Alzheimer Disease (AD)6,59
    DrugApproved IndicationSuggested DosageSide EffectsAdditional Notes/Caution
    Cholinesterase inhibitors
        Donepezil (Aricept)Mild to moderate ADOnce daily, beginning with 5 mg/day, which can be increased to 10 mg/day (maximum dosage) after 4 weeksAEs are mild and include nausea, vomiting, and diarrheaGastrointestinal-related AEs can be reduced if medication taken with food
    Some patients exhibit an initial increase in agitation, which subsides after first few weeks of therapy
    Severe AD
        Rivastigmine (Exelon)Mild to moderate ADOral: Twice daily, beginning with 1.5 mg
    Transdermal patch: Once daily, 4.6 or 9.5 mg
    The target dose is 9.5 mg/24 hr per patch (a 10 cm2 patch) and requires a simple one-step dose titration to the therapeutic dose
    There is a higher-dose patch (20 cm2) available, delivering 17.4 mg/24 hr; however, it is currently an unapproved treatment in the United States. Lack of approval was based on it having similar efficacy to the 10 cm2 patch, but with a tolerability profile comparable to that of the capsule formulation
    AEs include nausea, vomiting, diarrhea, weight loss, headaches, abdominal pain, fatigue, anxiety, and agitation
    Gastrointestinal-related AEs are less prominent with the patch: the 9.5 mg/24 hr patch provides efficacy similar to that of the highest dose of capsules, with 3 times fewer reports of nausea and vomiting
    Higher dosages are more efficacious than lower dosages
    No laboratory monitoring is required
        Galantamine (Razadyne)Mild to moderate ADTwice daily, beginning with 4 mg
    After 4 weeks, dosage is increased to 8 mg twice daily
    An increase to 12 mg twice daily can be considered on an individual basis after assessment of clinical benefit and tolerability
    Also available in an extended-release formulation that can be taken once daily
    Most common side effects are nausea, vomiting, and diarrheaGastrointestinal-related AEs can be minimized by titrating the dosage gradually and taking the medication with meals
    NMDA antagonist
        Memantine (Namenda)Moderate to severe ADTwice daily, beginning with 5 mg, increasing the dose to 10 mg twice daily over 3 weeksAEs include fatigue, pain, hypertension, headache, constipation, vomiting, back pain, somnolence, dizzinessModerate to severe AD may respond better with memantine/donepezil combination versus donepezil alone
    • AE, adverse event; NMDA, N-methyl D-aspartate.

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    Table 2. Nonpharmacologic Interventions for Reducing Behavioral Disturbances in Alzheimer Disease (AD)6,95
    SymptomResponse
    Indecisiveness
    • Reduce choices

    Disorientation
    • Provide the patient with a predictable routine (eg, exercise, meals, and bedtime should be routine and punctual)

    • Avoid relocation; if necessary bring familiar items

    • Allow the patient to dress in his or her own clothing and keep possessions

    • Use calendars, clocks, labels, and newspapers for orientation to time

    • Use color-coded or graphic labels (eg, on closets, table service, drawers) as cues for orientation in the home environment

    Hallucinations
    • Do not be overly concerned if they are not distressing to the patient

    • Consider antipsychotic agents where necessary, but fully inform family and caregivers of the risks/benefits of these medications

    Delusions
    • Redirect and distract the patient

    • Consider using antipsychotic medications

    Repetitiveness
    • Answer decisively, then distract

    Lack of motivation
    • Ensure tasks are simple so that the patient can complete them; break up complex tasks into smaller steps

    • Before performing all procedures and activities, explain them to the patient in simple language

    Wandering (usually occurs later in the disease, ie, moderate to severe AD)
    • Register the patient in the Alzheimer's Association Safe Return Program

    • Secure the environment with complex handles

    • Equip doors and gates with safety locks

    • Inform neighbors

    Agitation
    • Use distraction and redirection of activities to divert the patient from problematic situations

    • Reduce excess stimulation and outings to crowded places (overexposure to environmental stimuli can lead to agitation and disorientation)

    • Use lighting to reduce confusion and restlessness at night

    • Avoid glare from windows and mirrors, noise from a television, and household clutter

    Accident-prone
    • Provide a safe environment (eg, no sharp-edged furniture, no slippery floors or throw rugs, no obtrusive electrical cords)

    • Install grab bars by the toilet and in the shower

    Ensure that comorbid conditions are optimally treated
    Consider using a day care program for patients with AD
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    Table 3. Pharmacologic Treatment of Behavior and Mood Disorders
    Antipsychotic drugs
        Atypical antipsychotic agents
            Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness
            General cautions: diminished risk of developing extrapyramidal symptoms and tardive dyskinesia compared with typical antipsychotic agents
            Warning: atypical antipsychotic agents can cause an increased risk of cerebrovascular events (including stroke) in elderly patients with dementia-related psychosis
            Risperidone (Risperdal)Initial dosage: 0.25 mg/day at bedtime; maximum dosage: 2–3 mg/day, usually twice daily in divided dosesComments: current research supports use of low dosages; extrapyramidal symptoms may occur at 2 mg/day
            Olanzapine (Zyprexa)Initial dosage: 2.5 mg/day at bedtime; maximum dosage: 10 mg/day, usually twice daily in divided dosesComments: generally well tolerated
            Quetiapine (Seroquel)Initial dosage: 12.5 mg twice daily; maximum dosage: 200 mg twice dailyComments: more sedating; beware of transient orthostasis
        Typical antipsychotic agents
            Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness; second-line therapy for patients who cannot tolerate or who do not respond to atypical antipsychotic agents
            General cautions: current research suggests that these drugs be avoided if possible because they are associated with significant, often severe side effects involving the cholinergic, cardiovascular, and extrapyramidal systems; there is also an inherent risk of irreversible tardive dyskinesia, which can develop in 50% of elderly patients after continuous use of typical antipsychotic agents for 2 years
            Warning: typical antipsychotic agents can cause an increased risk of cerebrovascular events (including stroke) in elderly patients with dementia-related psychosis
            Haloperidol (Haldol), fluphenazine (Prolixin), thiothixene (Navane)Dosage: varies by agentComments: anticipated extrapyramidal symptoms; if these symptoms occur, decrease dosage or switch to another agent; avoid use of benztropine (Cogentin) or trihexyphenidyl (Artane)
            Trifluoperazine (Stelazine), molindone (Moban), perfenazine (Trilafon), loxapine (Loxitane)Dosage: varies by agentComments: agents with “in-between” side-effect profile
    Mood-stabilizing (anti-agitation) drugs
        Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness; useful alternatives to antipsychotic agents for control of severe agitated, repetitive, and combative behaviors
        General cautions: see comments about specific agents
        Trazodone (Desyrel)Initial dosage: 25 mg/day; maximum dosage: 200 to 400 mg/day in divided dosesComments: use with caution in patients with premature ventricular contractions
        Carbamazepine (Tegretol)Initial dosage: 100 mg twice daily; titrate to therapeutic blood level (4–8 μg/mL)Comments: monitor complete blood cell count and liver enzyme levels regularly; carbamazepine has problematic side effects
        Divalproex sodium (Depakote)Initial dosage: 125 mg twice daily; titrate to therapeutic blood level (40–90 μg/mL)Comments: generally better tolerated than other mood stabilizers; monitor liver enzyme levels; monitor platelets, prothrombin time, and partial thromboplastin time as indicated
    Anxiolytic drugs
        Benzodiazepines
            Recommended uses: management of insomnia, anxiety and agitation
            General cautions: regular use can lead to tolerance, addiction, depression and cognitive impairment; paradoxic agitations occurs in about 10% of patients treated with benzodiazepines; infrequent, low doses of agents with a short half-life are least problematic
            Lorazepam (Ativan), oxazepam (Serax), temazepam (Restoril), zolpidem (Ambien), triazolam (Halcion)Dosage: varies by agentSee general cautions
        Nonbenzodiazepines
            Buspirone (BuSpar)Initial dosage: 5 mg twice daily; maximum dosage: 20 mg 3 times dailyComments: useful only in patients with mild to moderate agitation; may take 2 to 4 weeks to become effective
    Antidepressant drugs
        Recommended uses: see comments on specific agents
        General cautions: selection of an antidepressant is usually based on previous treatment response, tolerance and the advantage of potential side effects (eg, sedation vs activation); a full therapeutic trial requires 4–8 weeks; as a rule, dosage is increased using increments of initial dose every 5–7 days until therapeutic benefits or significant side effects become apparent; after 9 months, dosage reduction is used to reassess the need to medicate; discontinuing an antidepressant over 10–14 days limits withdrawal symptoms.
        Note: patients with depression and psychosis require concomitant antipsychotic medications.
    Tricyclic antidepressant agents
        Desipramine (Norpramin)Initial dosage: 10–25 mg in the morning; maximum dosage: 150 mg in the morningComments: tends to be activating (eg, reduces apathy); lower risk for cardiotoxic, hypotensive and anticholinergic effects; may cause tachycardia; blood levels may be helpful
        Nortriptyline (Pamelor)Initial dosage: 10 mg at bedtime; anticipated dosage range: 10–40 mg/day (given twice daily)Comments: tolerance profile is similar to that of desipramine, but nortriptyline tends to be more sedating; may be useful in patients with agitated depression and insomnia; therapeutic blood level “window” of 50–150 ng/mL (190–570 nmol/L)
        Heterocyclic and noncyclic antidepressant agents
        Nefazodone (Serzone)Initial dosage: 50 mg twice daily; maximum dosage: 150–300 mg twice dailyComments: effective, especially in patients with associated anxiety; reduced dose of coadministered alprazolam (Xanax) or triazolam by 50%; monitor for hepatotoxicity
        Buproprion (Wellbutrin)Initial dosage: 37.5 mg every morning, then increase by 37.5 mg every 3 days; maximum dosage: 150 mg twice dailyComments: activating; possible rapid improvement of energy level; should not be used in agitated patients and those with seizure disorders; to minimize risk of insomnia, give second dose before 3pm
        Mirtazapine (Remeron)Initial dosage: 7.5 mg at bedtime; maximum dosage: 30 mg at bedtimeComments: potent and well tolerated; promotes sleep, appetite, and weight gain
    SSRIs
        Recommended uses: may prolong half-life of other drugs by inhibiting various cytochrome P450 isoenzymes
        General cautions: typical side effects include sweating, tremors, nervousness, insomnia or somnolence, dizziness, and various gastrointestinal and sexual disturbances
        Fluoxetine (Prozac)Initial dosage: 10 mg every other morning; maximum dosage: 20 mg every morningComments: activating, very long half-life; side effects may not manifest for a few weeks
        Paroxetine (Paxil)Initial dosage: 10 mg/day; maximum dosage: 40 mg/day (morning or evening)Comments: less activating but more anticholinergic than other SSRIs
        Sertraline (Zoloft)Initial dosage: 25–50 mg/day; maximum dosage: 200 mg/day (morning or evening)Comments: well tolerated; compared with other SSRIs, sertraline has less effect on metabolism of other medications
        Citalopram (Celexa)Initial dosage: 10 mg/day; maximum dosage: 40 mg/dayComments: well tolerated; some patients experience nausea and sleep disturbances
        Fluvoxamine (Luvox)Initial dosage: 50 mg twice daily; maximum dosage: 150 mg twice dailyComments: exercise caution when using fluvoxamine with alprazolam or triazolam
    • Reproduced with permission from Cummings JL, et al. Am Fam Physician 2002; 65:2525 to 2534. © 2002 American Academy of Family Physicians.6

    • SSRI, selective serotonin reuptake inhibitor.

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The Journal of the American Board of Family     Medicine: 25 (3)
The Journal of the American Board of Family Medicine
Vol. 25, Issue 3
May-June 2012
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Guidelines for the Management of Cognitive and Behavioral Problems in Dementia
Carl H. Sadowsky, James E. Galvin
The Journal of the American Board of Family Medicine May 2012, 25 (3) 350-366; DOI: 10.3122/jabfm.2012.03.100183

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Guidelines for the Management of Cognitive and Behavioral Problems in Dementia
Carl H. Sadowsky, James E. Galvin
The Journal of the American Board of Family Medicine May 2012, 25 (3) 350-366; DOI: 10.3122/jabfm.2012.03.100183
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    • The Role of the Family Physician in Treating Dementia
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