About half of individuals affected by Alzheimer’s disease (AD) will experience clinically significant depressive symptoms at some point. Depression can occur during early, middle, or later phases of the illness. The timing of depression during AD influences its characteristics and also help to determine the treatment approach that will be most likely to help.
How Alzheimer's Can Affect Mood
Alzheimer’s disease is now being diagnosed earlier and earlier, thanks to our growing use of biomarkers. Tests such as the amyloid PET scan can identify with a high degree of probability the presence of the AD process even when cognitive impairment is minimal or absent. AD interferes with the neurotransmitters that affect mood, even at an early stage of its development, so some researchers have suggested that depression early in AD is related to the disease’s primary brain-altering effects.
In addition, though, an early diagnosis can trigger a “reactive depression,” a depressive response to the serious news of disease and the specter of a severe future cognitive decline. As with other neurological disorders such as Huntington’s disease or stroke, depression in AD probably represents a debilitating mixture of reactive and primary influences.
Depression Can Cause a Dementia-Like Syndrome
Furthermore, there is also a famous “look-alike”: the so-called “dementia syndrome of depression” in which a person affected primarily by a depressive disorder experiences mental slowing and forgetfulness that suggests AD. In some of these people, depression later turns out to have been an early sign of oncoming dementia (now more correctly termed “Major Neurocognitive Disorder”), but many others experience significant cognitive improvement once the depression is treated.
Depression in the Middle and Late Stages of Alzheimer’s
As the damaging effects of AD intensify, depression can take on a different quality. Apathy is often prominent when depression emerges during AD’s middle stage, though classic depressive symptoms such as agitation, crying, the inability to experience pleasure (anhedonia), loss of appetite, suicidal ideation, and psychotic delusions may also occur. As neurocognitive impairment becomes even more severe, an affected person may be unable to remember symptoms of depression or to understand and articulate their meaning. Instead, in the late stages of the disease, disruptive behaviors such as resisting care, expressing delusions, or displaying increased agitation and even self-destructive behavior may provide clues of depression that insightful self-report no longer can reveal.
Treatment of depression in a person with AD differs in important ways from the treatment provided to individuals with depression who do not have dementia. Insight-oriented or behavioral psychotherapy, which are so helpful to depressed older adults with intact cognition or mild cognitive decline, can be useful during the earlier stages of AD, but these approaches are not considered likely to be helpful once the person with AD can no longer comprehend and retain information from session to session. Early on, the therapist’s role may include tasks somewhat unique to treating people with neurodegenerative disorders. The therapist may encourage the patient to consider long-range plans including estate planning and advance directives that will later guide others who take over financial management, residential decisions, treatment decisions, and implementation of end of life care wishes. Later in the course of AD, psychotherapy with a severely impaired person typically involves relieving symptoms and are oriented towards activities. The planning of pleasant events and the use of distraction and redirection are psychotherapeutic maneuvers suitable for use during AD’s later stages. Fun and engaging group activities that involve exercise or outings may be more soothing in late AD than therapy with the goal of increasing insight and understanding.
Medications: Understanding the Controversy
Cognitive enhancers, with their modest benefits for memory and activities of daily living, have not proven particularly beneficial in treating depression. Furthermore, the use of medications designed for the treatment of depression in people with AD and depression has been controversial. Despite several well-designed studies that showed antidepressant benefits among subjects with AD and depression, a similar number of other credible studies fail to differentiate the effects of antidepressants from those of placebo. A large, recent double-blind randomized controlled trial using sertraline in AD patients with depression failed to find significant benefits, though some of the study’s data suggest that antidepressant treatment may be of value in individuals with a severe and classic major depressive syndrome. In practice, many clinicians will prescribe an antidepressant, monitor its effects, but discontinue the medication if it is ineffective or if it causes significant adverse effects.
Potential Complications and Side Effects
The prescribing of medication for someone with AD and depression is often complicated by side effects or by the possibility of adverse interactions with one or more other medications prescribed for AD or co-existing medical conditions. Anticholinergic medications such as the tricyclic antidepressants are best avoided, given AD patients’ known deficiency of the neurotransmitter acetylcholine. When serotonergic antidepressants such as sertraline or citalopram, for example, are prescribed along with cholinesterase inhibitors, there may be a synergistic increase in gastrointestinal symptoms that either of these drug classes can produce. Doses of the antidepressant should be managed cautiously if patients show increased sensitivity to effects and side effects. If the medication is effective and the patient’s symptoms clear, discontinuation of the antidepressant may be appropriate after a period of months. Periodic re-evaluation of the need for an antidepressant in such patients plays the important role of limiting unnecessary medication therapy.
Discontinuing an antidepressant in some cases ushers in a depressive recurrence, so the pros and cons for such a discontinuation are weighed on a case by case basis.
For some, the antidepressant is a useful tool for short-term symptom relief, while others may benefit for a longer time period. Recent research, in fact, has suggested that some non-cognitive behavioral symptoms of Major Neurocognitive Disorder such as agitation can respond to treatment with a serotonergic antidepressant. Citalopram is the most thoroughly investigated medication in this regard, but some clinicians will try other medications in order to reduce the small but significant risk for an adverse effect on electrical conduction within the heart. Citalopram is recommended for use in older adults only at the dose of 20 mg/d (milligrams per day) or less.
Don’t Forget the Caregiver
In discussing the use of antidepressants in AD, mention must be made of caregivers, whose burden places them at increased risk for depressive disorders. Clinicians should remember to ask caregivers about their own physical and mental health, which are stressed by the demands of caregiving, and to refer when appropriate for support groups, psychotherapy, and medication therapy.
- Alzheimer’s Disease Toolkit (Helpful Information to Understand and Manage Alzheimer's Disease)
- Expert Information on Alzheimer's Disease (Articles)
- Dementia and Depression (Article)
This content was last updated on: November 9, 2020
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