Alzheimer's disease medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: , Sargun Singh Walia M.B.B.S.[2]

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Overview

There is no known cure for Alzheimer's disease (AD). Available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmacological, psychosocial, and caregiving. Acetylcholine esterase inhibitors increase the amount of acetylcholine in the brain and are a major part of pharmacotherapy for Alzheimer's disease. Major drugs include, donepezil, rivastigmine and galantamine, these drugs help with the cognitive symptoms of the disease. Associated psychosis and depression may be managed with antipsychotics and selective serotonin reuptake inhibitors (SSRIs). Caregiving plays a pivotal role in the management of patients suffering from Alzheimer's disease.

Medical Therapy

General considerations and medications

Alzheimer's disease (AD) has a high rate of progression and management is a combination of social support, behavioral modifications and pharmacotherapy. The following general considerations should be kept in mind when prescribing medications and coming up with a management plan for a patient suffering from Alzheimer's disease:

Management of psychological issues

Alzheimer's dementia is a chronic condition and is associated with significant distress not only for the patient but also for the caregivers. Optimum management should address the following issues when treating a patient with Alzheimer's dementia:

• Assessments of the following should be done:
  • Suicidal ideation
  • Potential of harm to self and others
  • Potential for aggression
  • Evaluation of living conditions, safety of the environment
  • Adequate supervision
  • Potential for neglect or abuse
• Important points in management of psychological issues involve the following:
  • Education of the patient and the caregivers
  • Patients and caregivers should be given the options of support groups, respite care, nursing homes, and other long-term-care facilities
  • Patients and their family should be made aware of potential incapacitation of the patient in the future, and should be advised to handle the financial and legal issues proactively

Management of cognitive symptoms

Acetylcholine-esterase inhibitors are used for the management of cognitive symptoms of Alzheimer's disease. The following drugs are used:

• Donepezil
• Rivastigmine
• Galantamine

NMDA receptor antagonist memantine is also used for managing cognitive symptoms

Management of psychosis and agitation

Psychosis and agitation sometimes accompany Alzheimer's disease and the following measures may be taken for successful management:

• Reassurance and redirection
• Antipsychotic pharmacotherapy (The choice of antipsychotic is individualized according to the patient and side-effect profile). The following antipsychotics may be used in combination with acetylcholinesterase inhibitors:
  • Risperidone
  • Haloperidol
  • Aripiprazole
  • Ziprasidone
• Benzodiazepines may also be used for management agitation in patients suffering from Alzheimer's disease:
  • Lorazepam
  • Oxazepam
  • Zolpidem

Management of depression

Depression is common in patients with dementia. The following medications may be used for the management of depression associated with Alzheimer's dementia:

• Selective serotonin reuptake inhibitors (SSRIs):
  • Citalopram
  • Bupropion
  • Venlafaxine
  • Mirtazapine
  • Unilateral electroconvulsive therapy (ECT)

Management of sleep disturbances

Pharmacological therapy may be used for concomitant sleep disturbances if other approaches fail. The following medications may be used as an adjunct:

• Trazodone
• Zolpidem
• Zaleplon

Fall prevention (especially in elderly)

A variety of interventions to prevent falls in elderly people have been proved to be effective:

• Withdrawal of medications associated with falls (especially those causing sedation, orthostatic hypotension)
• Use of canes, walkers and other support systems
• Environmental modifications including:
  • Removal of loose rugs, low tables, and other obstacles
  • Use of lower beds, night-lights, bedside commodes

Management of Alzheimer's disease according to severity

The American Psychiatric Association (APA) has published the following guidelines for the management of Alzheimer's disease, based on severity:

(a) Mild disease

• Patients may benefit from guidance for how to cope with minor disabilities
• The following suggestions may help the patient with dealing with daily life situations:
  • Making lists
  • Calendar use to maintain time orientation
  • Avoiding overwhelming situations such as certain childcare responsibilities
  • Health promotion activities
  • Joining recreation clubs
  • Assessment of co-morbid conditions such as major depression
• 1 Mild to moderate Alzheimer's disease
  • 1.1 Adult
    • Preferred regimen (1): Donepezil 5 mg PO once daily; may increase to 10 mg once daily after 4 to 6 weeks
    • Preferred regimen (2): Rivastigmine 1.5 mg PO twice daily; may increase by 3 mg daily (1.5 mg/dose) every 2 weeks based on tolerability (maximum recommended dose: 6 mg twice daily
    • Preferred regimen (3): Galantamine immediate-release tablet or solution: Initial: 4 mg twice daily for 4 weeks; if tolerated, increase to 8 mg twice daily for ≥4 weeks; if tolerated, increase to 12 mg twice daily (Range: 16 to 24 mg daily in 2 divided doses)
    • Alternative regimen (1): Rivastigmine transdermal patch: Apply 4.6 mg/24 hours patch once daily; if well tolerated, may titrate (no sooner than every 4 weeks) to 9.5 mg/24 hours (continue as long as therapeutically beneficial), and then to 13.3 mg/24 hours (maximum dose); doses >13.3 mg/24 hours have not been shown to be more effective and are associated with significant increases in adverse events (Recommended effective dose: Apply 9.5 mg/24 hours or 13.3 mg/24 hours patch once daily; remove old patch and replace with a new patch every 24 hours)
    • Alternative regimen (2): Galantamine extended release capsule 8 mg once daily for 4 weeks; if tolerated, increase to 16 mg once daily for ≥4 weeks; if tolerated, increase to 24 mg once daily. Range: 16 to 24 mg once daily
  • 1.2 Renal impairment
    • Preferred regimen (1): Donepezil:
      • No adjustment required
    • Preferred regimen (2): Rivastigmine:
      • No adjustment required
    • Preferred regimen (3): Galantamine:
      • Mild impairment: No dosage adjustment required
      • Moderate impairment (Creatinine clearance [CrCl] 9 to 59 mL/minute): Maximum dose: 16 mg/day.
      • Severe impairment (CrCl <9 mL/minute): Use is not recommended
  • 1.3 Hepatic impairment
    • Preferred regimen (1): Donepezil:
      • No adjustment required
  • Preferred regimen (2): Rivastigmine:
    • No adjustment required
  • Preferred regimen (3): Galantamine:
    • Mild impairment (Child-Pugh class A): No dosage adjustment required
    • Moderate impairment (Child-Pugh class B): Maximum dose: 16 mg/day
    • Severe impairment (Child-Pugh class C): Use is not recommended

(b) Moderate disease

• Caregivers are an important part of management of moderate severity Alzheimer's disease
• The following suggestions and advice should be given to the caregivers of the patients:
  • Caregivers should be advised about the possibility of accidents due to forgetfulness (e.g., fires while cooking), of difficulties coping with household emergencies, and of the possibility of wandering.
  • Caregivers should also be advised to asses if the patient is handling finances appropriately and to consider taking over the financial matters requiring memory function and cognition for example, paying bills and maintenance of bank accounts.
  • Patients should not be allowed to drive
  • Consider home health aid, day care, brief assisted living, or nursing home stay
• 1 Mild to moderate Alzheimer's disease
  • 1.1 Adult
    • Preferred regimen (1): Donepezil 5 mg PO once daily PLUS immediate release memantine PO 5 mg daily; increase dose by 5 mg daily to a target dose of 20 mg daily; wait ≥1 week between dosage changes. Doses >5 mg daily should be given in 2 divided doses
    • Preferred regimen (2): Donepezil 5 mg PO once daily PLUS extended release memantine PO 7 mg once daily, increase dose by 7 mg daily to a target maximum dose of 28 mg once daily; wait ≥1 week between dosage changes (if previous dose well tolerated)
    • Alternative regimen (1): Donepezil 5 mg PO once daily PLUS aripiprazole IM immediate release 9.75 mg as a single dose (range: 5.25 to 15 mg; a lower dose of 5.25 mg IM may be considered when clinical factors warrant); repeated doses may be given at ≥2-hour intervals to a maximum of 30 mg/day
    • Alternative regimen (2): Donepezil 5 mg PO once daily; may increase to 10 mg once daily after 4 to 6 weeks
    • Aternative regimen (3): Donepezil 5 mg PO once daily; may increase to 10 mg once daily after 4 to 6 weeks PLUS carbamazepine PO 100 mg once or twice daily for 6 to 8 weeks
    • Alternative regimen (4): Donepezil 5 mg PO once daily PLUS citalopram 10 mg PO once daily; increase the dose by 20 mg at an interval of ≥1 week to a maximum dose of 40 mg daily
    • Alternative regimen (5): Donepezil 5 mg PO once daily PLUS sertraline 12.5 mg PO; increased at 1–2-week intervals up to a maximum dosage of 150–200 mg/day
    • Alternative regimen (6): Donepezil 5 mg PO once daily PLUS extended release venlafaxine PO 37.5 mg/day; increased at approximately weekly intervals up to a maximum dosage of 375 mg/day in divided doses
    • Alternative regimen (7): Donepezil 5 mg PO once daily PLUS dextroamphetamine PO 2.5–5.0 mg/day
    • Alternative regimen (8): Donepezil 5 mg PO once daily PLUS methylphenidate PO 2.5-5.0 mg/day
    • Alternative regimen (9): Donepezil 5 mg PO once daily PLUS trazodone PO 25-100 mg/day
    • Alternative regimen (10): Donepezil 5 mg PO once daily PLUS zolpidem PO 5-10 mg/day

(c) Severe disease

• Patients with severe disease are grossly incapable of carrying out basic daily life activities such as, getting dressed, bathing and feeding
• Caregivers are again a major part of the management of severe disease
• Family meetings and rigorous counselling sessions are important to make families aware of the problem, and to avoid frustration
• Caregivers may be given the option of transferring the patient to a nursing home for close monitoring and better care
• 1 Severe Alzheimer's disease
  • 1.1 Adult
    • Preferred regimen (1): Donepezil 5 mg PO once daily PLUS immediate release memantine PO 5 mg daily; increase dose by 5 mg daily to a target dose of 20 mg daily; wait ≥1 week between dosage changes. Doses >5 mg daily should be given in 2 divided doses
    • Preferred regimen (2): Donepezil 5 mg PO once daily PLUS extended release memantine PO 7 mg once daily, increase dose by 7 mg daily to a target maximum dose of 28 mg once daily; wait ≥1 week between dosage changes (if previous dose well tolerated)
    • Alternative regimen (1): Donepezil 5 mg PO once daily PLUS aripiprazole IM immediate release 9.75 mg as a single dose (range: 5.25 to 15 mg; a lower dose of 5.25 mg IM may be considered when clinical factors warrant); repeated doses may be given at ≥2-hour intervals to a maximum of 30 mg/day
    • Alternative regimen (2): Donepezil 5 mg PO once daily PLUS citalopram 10 mg PO once daily; increase the dose by 20 mg at an interval of ≥1 week to a maximum dose of 40 mg daily
    • Alternative regimen (3): Donepezil 5 mg PO once daily PLUS sertraline 12.5 mg PO; increased at 1–2-week intervals up to a maximum dosage of 150–200 mg/day
    • Alternative regimen (4): Donepezil 5 mg PO once daily PLUS extended release venlafaxine PO 37.5 mg/day; increased at approximately weekly intervals up to a maximum dosage of 375 mg/day in divided doses

Caregiving

Further information: [[:Caregiving and dementia]]

Since there is no cure for Alzheimer's, caregiving is an essential aspect of the management of the disease. Due to the eventual inability of the sufferer to self-care, Alzheimer's disease (AD) has to be carefully care-managed. Home care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care. Many family members choose to look after their relatives with Alzheimer's disease, but two-thirds of nursing home residents have dementias.

Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes. Appropriate social and visual stimulation can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.

References

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