Psychiatric symptoms of dementia: Treatable, but no silver bullet
ABSTRACTBehavioral problems are common in dementia and may reduce the quality of life of the patient and disrupt the home life of family members. Families want a pill that can cure the myriad phenotypes of a decaying brain; unfortunately, there is no pharmaceutical silver bullet. This paper reviews the evidence for using different classes of drugs for the behavior symptoms commonly encountered in dementia, focusing on concerns that the primary care physician would have about using these drugs.
KEY POINTS
- No drug specifically addresses wandering, hoarding, or resistance to care, behaviors that are particularly frustrating to caregivers.
- Many drugs are sedating and increase the risk of falling and injury; antipsychotic use is off-label for dementia and carries significant and possibly lethal adverse effects.
- Managing the behavioral symptoms of dementia requires attention to the environmental and psychosocial context in which they occur, as well as to comorbidities and potential adverse drug effects.
- Evidence for the efficacy of antidepressants for depression in dementia is limited.
No data on treating apathy
Apathy in elderly patients with dementia is common. It is found in nearly half of elderly patients with mild dementia and in nearly all of those with severe dementia. If accompanied by depressive symptoms such as sadness, guilt, feelings of worthlessness, passive or active death wish, changes in sleep or appetite, or tearfulness, apathy and other depressive symptoms may respond to antidepressive treatment—both behavioral and pharmacologic. When present in dementia without depressive symptomatology, apathy is unlikely to respond to antidepressants. In particular, SSRIs may actually induce or worsen apathy through their effect on the angular gyrus. Apathy can be very frustrating to family members but not troublesome at all to the patient.
No medication carries an indication for apathy in dementia. Although stimulants such as methylphenidate and modafinil (Provigil) have been used, there is no evidence to date from any controlled study of efficacy and safety in this population.
Try nondrug measures concomitantly
Given the limited evidence of efficacy of antidepressive therapy in demented elderly patients, nonpharmacologic therapy should be offered concomitantly.
Evidence-based nonpharmacologic treatment for depression in dementia includes increasing enjoyable activities and socialization with people and pets, reducing the need to perform frustrating activities, redirecting perseverative behaviors and speech, and addressing caregiver needs.34 Exercise may improve physical functioning in depression with dementia.35 A comprehensive sleep program may improve associated sleep disorders.36
An intensive collaborative-care intervention37 resulted in more demented elderly patients in the intervention group receiving a cholinesterase inhibitor and an antidepressive than in the usual-care group. Outcomes included fewer behavioral symptoms, less caregiver distress, and less caregiver depression.
So far, no randomized trial has shown electroconvulsive therapy to be effective in elderly patients with depression and dementia.38
ANTICONVULSANT DRUGS MAY STABILIZE MOOD
On the basis of small studies with some contradictory outcomes,39 both older and newer anticonvulsants have been used in nonpsychotic agitation, aggression, and impulsivity in a variety of psychiatric disorders, brain injury, and dementia.40 Most of the data are on the older drugs such as valproic acid and carbamazepine (Tegretol).
Valproic acid is associated with an adverse metabolic profile (hyperglycemia, weight gain, and hyperlipidemia),41,42 dose-related orthostasis, sedation, and worsening cognitive performance. In addition, the possibility of thrombocytopenia and blood level fluctuations requires monitoring. Older adults may tolerate 250 to 500 mg/day with minimal adverse effects.
Carbamazepine reduced aggression in a blinded, placebo-controlled study in nursing home patients.43 Use of carbamazepine requires monitoring of hematologic and liver profiles, alters the metabolism of itself and other drugs, and is associated with dose-related sedation.
Lamotrigine (Lamictal) takes a long time to titrate but may help with nonpsychotic agitation and impulsivity; it is a relatively new drug, and there are limited data to support its use at this time in the elderly.
Gabapentin (Gabarone), in case reports at doses primarily from 600 to 1,200 mg/day, reduced behavioral and psychological problems of patients with dementia and with good renal clearance.44 Some patients may experience tremors or oversedation.
Phenytoin (Dilantin) is not a good choice for behavioral problems because of unwanted effects on teeth, bones, and balance.
Levetiracetam (Keppra) may cause behavioral disturbances to emerge or worsen.45
Emerging evidence suggests that all anticonvulsants may also be associated with an increased risk of depressive symptoms.
COGNITIVE ENHANCERS MAY IMPROVE BEHAVIOR
Acetylcholinesterase inhibitors may improve some behavioral symptoms of dementia. In an open-label retrospective trial, delusionality, irritability, anxiety, disinhibition, and agitation improved in some patients on these drugs.46 Patients most likely to respond were those with the most impairment from these behaviors and those with depressive or apathetic symptoms.46 A Cochrane review found a modest beneficial effect on behavior.47
Acetylcholinesterase inhibitors may reduce symptoms of apathy. Additionally, they actually improve depressive symptoms in mild to moderate dementia independent of any effect on cognition.48
Memantine (Namenda), approved for the treatment of moderate to severe dementia, may reduce the prevalence and incidence of agitation, particularly in more advanced dementia.49
The cognitive enhancers all require several weeks for titration and are not helpful for the acute management of behavioral or depressive symptoms.
OTHER DRUGS
Beta-blockers50 and estrogen51 have been studied as off-label, nonneuroleptic treatments for male aggression. Use of progesterone in men with inappropriate sexual behavior52 may have benefit; further interventions are reviewed by Srinivasan and Weinberg.53 These recommendations are based on small case series. In addition, the hormonal treatments may carry significant morbidity.
Sedative hypnotics were evaluated for sleep difficulties in demented patients in a meta-analysis by Glass et al,54 who found adverse cognitive events, psychomotor events, and daytime fatigue more common (5, 2.6, and 3.8 times, respectively) in the sedative group than in the placebo group.
For agitation in delirium, haloperidol (Haldol) is preferable to benzodiazepines, based on studies from the 1970s.55 Although benzodiazepines carry an indication for anxiety, newly prescribed benzodiazepines and those with a longer half-life are associated with hip fractures in older adults,56 possibly from sedation.
