A Shift in the Paradigm of Treatment

This column will be a regular feature of Psychiatry 2006 reviewing current psychosocial and psychotropic advances in the treatment of Alzheimer's disease.

The paradigm for treating patients with Alzheimer's disease (AD) has totally changed over recent years.¹ The goal used to be to merely sustain survival and provide palliative care to the patient. Now the goal is to provide maximal benefits at all stages of this disease, or at least until the patient's burdens greatly outweigh treatment benefits.² For example, some argue that life-sustaining measures, such as artificial feeding, should be stopped if and when the burden of living becomes too great for the patient.³

There are several reasons for this change. Chief among these reasons are the following: 1) Medications now have much to offer—they still cannot cure this disease, but they often can significantly slow down its progression. Most importantly, this advance enables patients with AD to stay at home longer as opposed to requiring care at a nursing home.⁴ This difference may mean everything to these patients and their families.

Recent data suggest that patients who experience early difficulty with their memories but do not have AD may be at greater risk of developing this disease later.⁵ New technical developments, such as in neuroimaging, may allow clinicians to make this diagnosis before these patients experience any cognitive decline.⁶ This may enable patients to benefit from the available medications even earlier. Some data suggest that a majority of persons would want this early testing and treatment.⁷ If these same patients also have depression, treatment for their depression may also benefit their AD later.^8,9 Consequently, the threshold and criteria for giving antidepressants may, for patients at higher risk, at some time warrant being reduced.

It is now better recognized that despite a patient's cognitive impairments, he or she may continue to be appropriately emotionally responsive to others. Accordingly, clinicians should provide a patient with AD with psychosocial therapy. More importantly, perhaps, clinicians should provide psychosocial therapy to the family member(s) who cares for the patient with AD—this helps the family member gain optimal caregiving skills since he or she spends so much time with the patient.^10,11

It is often critical for patients with AD to receive help for agitation and aggression because these are the behaviorial disturbances that most often cause these patients to be placed in nursing homes.¹² Initially, clinicians should rule out other causes of these symptoms, such as pain, bladder distention, or fecal impaction.^13–16 The three predominant approaches for treating patients with AD are providing psychotherapy to the patients, educating and providing psychotherapy to the family members caring for the patients, and the use of medications. All three approaches include promising new developments and are reviewed here.

Psychotherapy for the Patient

Clinicians can use modifications of cognitive behavioral therapy during the earliest stages of AD to try to help these patients not only overcome depression, but gain better interpersonal skills.¹⁷ Cognitive approaches are most effective in the earliest stages of AD, but they may be effective only for a limited amount of time.¹⁸ As a patient's dementia becomes more advanced, clinicians can use more behaviorally oriented approaches.^18,19These approaches may improve the patient's behavior even after his or her dementia has become severe.¹⁸ As this change in treatment illustrates, psychological approaches can be tailored specifically according to each patient's capacity to learn as he or she continues to experience increasing deficits.^20–22 Patients with AD also may benefit significantly from participating in other noncognitive activities, such as music, art therapy, and therapies involving touch, dancing, and interaction with pets.^23,24 This may be, in part, because these patients are less impaired in these areas. Also, patients with AD have reported that when they participate in these types of activities with other patients with AD, they no longer feel as self-conscious about their cognitive deficits. Rather, they feel again more “like themselves.”²⁴ They may also benefit, in part, from physical exercise.²⁵

The purported benefits from many of these interventions are primarily anecdotal and have not been empirically proven by studies meeting scientific levels of proof.¹⁹ The absence of this evidence may, however, be less critical clinically than usual for several reasons. For example, these studies may be more difficult to conduct in a “blind” manner; it may be necessary to individualize these treatments according to each patient's needs for them to be effective; and many of the patients studied have comorbid conditions that have not been excluded and can affect the results.²³

Psychotherapy for the Family Members

Clinicians may help patients with AD indirectly by addressing the needs of their primary caregivers, who are often family members.^26,27 As mentioned previously, family members may benefit these patients more if they can acquire optimal skills for responding to patient needs, such as knowing how to best respond to certain emotions displayed by these patients (e.g., anger).^28–30 Family members can better care for patients with AD if they are educated about the different stages of the disease and how to adjust their care accordingly. For example, at earlier stages, family members can prepare a life-story book to share with the patient frequently; this can help remind the patient of important times in his or her life. In the last phase of a patient's illness, family members can learn to talk to the patient soothingly as they feed, bathe, dress, and move him or her.³⁰ Special programs have now been designed to help family members acquire these skills.³¹

Since family members may benefit patients with AD significantly by acquiring these skills, clinicians should take the initiative to educate family members regarding these potential benefits. Clinicians can also help to motivate family members to pursue this learning by informing them that these skills are not those they would necessarily acquire in their everyday lives and that some skills are counterintuitive, such as being caring even when a patient becomes angry and aggressive.

Use of Medication

Medication may be critical in maximizing the quality of life for patients with AD, but may cause many difficult clinical decisions for the clinician, as discussed in the following paragraphs.

The core treatments for maintaining and enhancing the cognitive capacities of patients with AD are cholinesterase inhibitors, such as donepezil, and the NMDA-antagonist memantine. These two classes of medication have been most strongly indicated during the mild and moderate (donepezil) and severe (memantine) stages of AD, but a question clinicians may be confronted with is: When should these drugs be used in ways that are offlabel? Should these drugs be used, for example, during other stages of the disease in which their efficacy is less established? When, if ever, should these drugs be combined?^32–35

A second category of medications that may cause more difficult questions for the clinicians are those that can potentially reduce patient agitation and psychotic symptoms. The key question here is: When should antipsychotic drugs, particularly the atypicals, be used in patients with AD? This question is difficult because these medications may cause these patients greater morbidity and death.³⁶ The use of atypical antipsychotics “sparingly” in this patient population is now the offlabel treatment of choice, especially since the benefits of alternative treatments, such as the anticonvulsants, remain less clear.^37–41

When patients with AD have concomitant depression, selective serotonin reuptake inhibitors (SSRIs) may be helpful.^42–45 Exceptional precautions are those that clinicians would expect with non-geriatric patients. Chief among these precautions are the emergence of suicidality and associated behaviors, such as agitation, irritibility, and impulsivity; SIADH (syndrome of inappropriate secretion of antidiuretic hormone) with hyponatremia, which increases with age (often presenting with urinary incontinence, hypotension, nausea, vomiting, headache, fatigue, and confusion); and serotonin syndrome, especially when SSRIs are combined with other drugs (often presenting with hyperthermia, nausea, diarrhea, chills, dizziness, palpitations, muscular rigidity, and agitation). Clinicians should start with low dosages, titrate slowly, and be alert to cognitive effects that these drugs and their combinations with other medications might create.⁴⁶

Clinicians should also consider what to do when patients periodically become extremely agitated in their homes. As discussed earlier, agitation and aggression in patients with AD make it increasingly difficult for family members to take care of them in their homes. Yet these patients may remain willing to take small doses of antipsychotic medication administered by their family members at times to help calm them down. Under these circumstances, clinicians can provide the family members with small amounts of additional antipsychotic medication in the event a patient becomes extremely agitated. This not only may help a patient immediately, but it may enable him or her to live at home longer with his or her family. Should psychiatrists accept and implement this?

As medications prove beneficial, means must be found to help pay for them.^23,47 A paradigmatic example is vagal nerve stimulation (VNS). This relatively expensive mode of treatment has been found to be help some patients with AD and depression when other first-line treatments for depression have failed.⁴⁸ Yet, some argue that clinicians should not administer costly treatments such as this on account of a patient's advanced age.⁴⁹ The ethical bases of allocating funds to be able to give patients with AD effective but costly treatments, such as VNS, may need to be newly debated.

Conclusion

Perhaps the best approach to treating patients who may later have AD, however, will be to intervene prior to symptom occurrence.⁵⁰ This means identifying persons at high risk when they still have normal cognition and initiating treatment then.⁵¹ One expert states, for example, based on current research, “Plaques and tangles that have captivated our visual attention for a century may not be the key targets for effective therapies after all.”⁵²

This early recognition is already possible, for instance, when patients have the APOE gene and exceptional findings in their cerebral spinal fluid.⁵¹ Interventions before symptoms occur might be cheaper and more effective. Moreover, they might reduce the deterioration these patients experience to such an extent that this may enable many more patients to be able to remain at home.