Agitation and Depression in Older Patients

TCPR: Why don’t we start with the issue of agitation? The question in many psychiatrists’ minds is how seriously we should take the FDA advisory about the dangers of atypical antipsychotics?

Dr. Ellison: Seriously but not definitively. The concern about antipsychotics in the elderly began several years ago with an Australian study of demented patients with psychotic symptoms (Brodaty H et al., J Clin Psychiatry 2003;64(2):134-43). In that study, risperidone was more effective than placebo for the treatment of agitation, but it was associated with an increased rate of cerebrovascular adverse events; Janssen disclosed this information to the FDA, resulting in a 2003 warning about cerebrovascular adverse event risk in psychotic demented patients. Then in 2005, further analysis of adverse event data led the FDA to assign a class warning to the atypicals regarding an “increased risk of death compared to placebo” in the treatment of “elderly patients with dementia-related psychosis.” In October 2006, the results of the CATIE-AD study didn’t reassure clinicians about the atypicals’ effectiveness in treating agitation in demented patients. The atypicals outperformed placebo but were associated with significant adverse effects for a relatively modest benefit (Schneider LS et al., N Engl J Med 2006;355:1525-1538). Many clinicians have since been looking for alternatives such as citalopram, anticonvulsants, anxiolytics, or typical antipsychotics, though it’s not clear that any alternative choice is associated with both better efficacy and greater safety.

TCPR: And what is your take on the risks of antipsychotics?

Dr. Ellison: We don’t have good alternatives yet – but these days I’ll consider using a cholinesterase inhibitor or memantine (Namenda), an SSRI such as citalopram, or an anticonvulsant if the agitation is mild. For psychosis, a typical neuroleptic is probably no less dangerous than an atypical. Any psychotropic (but especially the atypical antipsy-chotics) should be used at lowest effective dose for the shortest necessary time in thisfragile population.

TCPR: Is there any other new information about antipsychotics in the elderly thatwe should be aware of?

Dr. Ellison: An interesting point that we sometimes fail to consider is that cognitiveperformance can be negatively affected by the atypical antipsychotics. Schneider comments onthis in his outstanding review (Schneider LS et al., Am J Geriatr Psychiatry 2006;14:191-210). The mean decrease he notes in MMSE scores with atypicals is of a similar magnitude tothe gain we see with the cholinesterase inhibitors, so it is probably of clinical significance.

TCPR: What are the medications that have the best data to support this risk of a cognitive decline?

Dr. Ellison: Less data are available about ziprasidone (Geodon) and aripiprazole (Abilify) than about olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine (Seroquel).

TCPR: Let’s move on to the issue of late-life depression. Does depression present differently in older patients?

Dr. Ellison: It can. Instead of complaining about “depression” or “sadness,” you may hear depressed elders talk about “weariness” or “nerves.” In addition, you might notice more of a behavioral presentation: these patients might be withdrawn or irritable; they are no longer as interested in hobbies or social activities; they might talk about having “lived long enough” and feeling “ready for death.” There are often prominent somatic symptoms, and a number of patients are afraid that they are “losing their mind” and that they are developing dementia. We have to avoid taking that worry at face value, since depressed patients can be erroneously diagnosed as demented and then inappropriately institutionalized in a nursing home.

TCPR: What is “pseudo-dementia?”

Dr. Ellison: Pseudo-dementia is a very interesting term because it is not exactly dementia, and it is also not exactly “pseudo;” it was considered a reversible cognitive impairment attributable to depression but is often only partially reversible through treatment of depression. Typically, pseudo-demented patients are depressed and also complain of profound difficulties with memory and concentration. If you follow these patients, they have a greater risk of eventually converting to dementia. So that raises the question of whether depression is a prodrome of dementia. Or, and this is a possibility that would heighten the importance of treating depression aggressively, does depression in some way hasten the onset or increase the risk of dementia?

TCPR: Are there particular kinds of questions that we should be asking elderly patients to diagnose depression?

Dr. Ellison: Yes, and many of these questions are on the Geriatric Depression Scale, which is an excellent 15 item scale that is in the public domain [Ed. Note: This scale is easily accessed by doing a Google search; one site allowing you to score it online is http://www.stanford.edu/~yesavage/Testing.htm]. It asks questions like: “Have you dropped many of your activities and interests? Do you feel like your life is empty? Do you feel worthless? Do you feel that most people are better off than you are?” So you can see that the approach is somewhat different than the DSM-IV where you are asking about such neurovegetative symptoms as sleep and appetite, both of which are frequently disturbed in the elderly for reasons other than depression.

TCPR: What is there to say about specific treatment for late-life depression?

Dr. Ellison: The first thing to clarify is that antidepressants do, indeed, work in the elderly. There are over 70 randomized controlled trials of the pharmacotherapy of geriatric depression, and the average response rate to medication is 50-65% compared to a 25-30% placebo response. Remission rates are 30-40% for drug vs. 15% for placebo. So, in terms of a number-needed-to-treat, that would be 4-7.

TCPR: So medications do work. Which ones should we choose?

Dr. Ellison: I’ll tell you my opinion about this. Let’s go through the potential differences between antidepressants and how these apply to treating elders. All the antidepressants have been shown to be efficacious, so if we try to decide on the basis of efficacy we wouldn’t be able to make a choice. Likewise, if we go on the basis of FDA indication, this doesn’t help us because the only drug that is FDA-approved for late-life depression is Prozac (fluoxetine), which hasn’t been convincingly shown superior to other antidepressants in this role. The next factor to consider is cost, because even though there is prescription coverage under Medicare Part D, nonetheless as costs go up the patient is pushed into the expensive so-called “donut hole.”

TCPR: Can you explain what the Part D donut hole is, exactly?

Dr. Ellison: With Medicare Part D there is an upfront deductible after which most of the cost of the medication is covered by Medicare up to a limit. Beyond that limit, the patient becomes fully responsible for the cost, until the cost reaches a certain point, and then catastrophic coverage kicks in. The more costly medications push the patient up more quickly to that donut hole where they become fully financially responsible. The point is, we should always go with less expensive generic medications initially, and there are excellent generics available. The only ones that are not generic would be Lexapro, Paxil CR, Effexor XR, Cymbalta, and Emsam, and there are generics for everything else.

TCPR: What other factors should we consider?

Dr. Ellison: Then the next factor is side effects. And a meta-analysis comparing the tricyclics to the newer antidepressants came up with the conclusion – no big surprise – that the newer drugs are a little bit more tolerable, but actually not as much more tolerable as you might have thought. To some extent, there is a different domain of side effects. With the tricyclics you experience cardiac complications, dry mouth, constipation, drowsiness, dizziness, lethargy, but with the new drugs there is sexual dysfunction, gastrointestinal symptoms and sleep disturbance. And the elderly can have sleep disturbances anyway, so sometimes that is an issue.

TCPR: What about issues of pharmacokinetics?

Dr. Ellison: That’s crucial, especially drug-drug interactions. The average patient at age 65 is on five prescribed medications and the average patient at age 75 is on eight prescribed medications.

TCPR: So what’s the bottom line?

Dr. Ellison: The bottom line is that if you look at all of the available antidepressants you could say that sertraline (Zoloft) and citalopram (Celexa) are available generically, have an appropriate amount of evidence of tolerability and efficacy in the elderly; their half-life is right for once-a-day dosing; they are not likely to produce discontinuation symptoms; their drug-drug interactions are minimal; and they don’t produce anticholinergic effects or postural hypotension.

TCPR: So your favorites are sertraline and citalopram. Are there any others that you consider in this population?

Dr. Ellison: There are four others that I often use. I use nortriptyline because with monitoring of the blood level it can be dosed in such a way that it is very tolerable and effective. Venlafaxine (Effexor) is an alternative that has dual neurotransmitter effects. Bupropion (Wellbutrin), a more stimulating drug, may be helpful with some patients who present with apathy. Finally, mirtazapine (Remeron) may be useful in patients with significant anxiety, insomnia and anorexia.

General Psychiatry