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.
ANTIDEPRESSANTS: MANY CHOICES, LITTLE EVIDENCE
Depression is hard to assess in a patient with dementia, particularly since apathy is a common symptom in both dementia and depression and may confuse the presentation. Additionally, screening tests for depression have not been validated in the demented elderly.
Depression in dementia is associated with poorer quality of life, greater disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement, a higher death rate, and a higher frequency of depression and burden in caregivers.19 Quality of life may improve with antidepressant treatment even if the patient does not meet all the criteria for a major depressive disorder. Provisional recommendations for diagnosing depression in dementia suggest using three (instead of five) or more criteria, and include irritability or social isolation as additional criteria.20
Choosing an antidepressant
Only a few randomized controlled trials of antidepressants for depression with dementia have been completed, each with a small number of patients.
Mirtazapine (Remeron) is what we recommend to improve sleep and appetite and restore lost weight.21 It can be used in patients with Parkinson disease or parkinsonian symptoms who experience increased tremors or bradykinesia with selective serotonin reuptake inhibitors (SSRIs). On the other hand, it may not be the best option for those with diabetes mellitus, metabolic syndrome, hyperlipidemia, or obesity. It may rarely also cause a reversible agranulocytosis.
Venlafaxine (Effexor) and duloxetine (Cymbalta) are serotonin-norepinephrine reuptake inhibitors (SNRIs) and may help in concomitant pain syndromes.22 Either drug can cause anorexia at any dose and can elevate blood pressure at higher doses. Venlafaxine may also cause insomnia in some patients.
Bupropion (Wellbutrin) can be difficult to titrate to an effective dose in an older person with unsuspected renal insufficiency, and it may interact at the P450 complex.23 The risk of seizures is greater at higher bupropion serum levels. There is also a high incidence of weight loss. Frail elderly patients, those with hypertension, and those vulnerable to hallucinations will likely do better with another drug.
Nefazodone is a third- or fourth-line antidepressive choice because of the risk of hepatic failure. However, it can help reduce disabling anxiety associated with depression. The FDA requires periodic liver function testing if this drug is used.
Trazodone in low doses (≤ 100 mg) each evening may help with sleep, but it cannot be titrated to antidepressive doses in older adults because of orthostatic effects.
Nortriptyline is recommended by some geriatricians for depression or pathologic crying in patients with mixed vascular dementia. However, it often causes cardiac conduction delays with reflex sympathetic tachycardia and anticholinergic side effects.
Monoamine oxidase inhibitors interact with many foods and drugs, limiting their use in older adults.
Methylphenidate (Ritalin) at low doses is used off-label for depression in palliative care, with noted rapid improvements in mood and appetite.24 Monitoring for increases in blood pressure, heart rate, and respiratory rate is essential if this stimulant is chosen. Patients who respond may make a transition to other traditional drugs after 2 to 4 weeks.
Caveats with SSRIs
- Despite the safety profile of SSRIs in older adults, care must be taken when prescribing them to frail elderly patients, given recent data associating SSRIs with falls and fragility fractures25,26 and urinary incontinence.27
- SSRIs may decrease appetite during initial treatment.
- Sertraline (Zoloft) may have to be started at a very low dose to decrease possible adverse gastrointestinal symptoms, such as diarrhea.
- Paroxetine (Paxil) has multiple interactions at the cytochrome P450 complex and has the most anticholinergic properties of the SSRIs, rendering it more likely to cause adverse drug reactions, constipation, and delirium.
- Daily fluoxetine (Prozac) may not be appropriate in older adults because of its long half-life and the risk of insomnia and agitation.28
- Tremors can emerge with all the SSRIs; akathisia, dystonia, and parkinsonism are also possible.29
- Hyponatremia, bruising, and increased bleeding time can occur with any SSRI.
- Abrupt cessation of any SSRI except fluoxetine (due to its long half-life) or of SNRIs may cause a very unpleasant flu-like withdrawal syndrome.
- Apathy can be a reversible, dose-dependent adverse effect of SSRIs in young persons30; there are no data on the dose at which this adverse effect might emerge in demented elderly patients.
In a systematic review, Sink et al31 found citalopram (Celexa) to help reduce nondepressive agitation.
How long should depression be treated?
Antidepressant treatment is typically for 6 to 12 months. However, the optimal duration in an older adult with dementia is not known and is not addressed in either the American Psychiatric Association practice guideline on dementia32 or the position statement of the American Association for Geriatric Psychiatry.33
Patients with executive dysfunction, particularly those with perseveration and diminished inhibition, may be less likely to respond to antidepressants, and the symptoms are more likely to recur if they do respond.34 It may be appropriate to treat them for a year and then withdraw the drug and monitor for recurrence. Some patients may need indefinite treatment.
