Real World Health Care recently sat down with Anton Porsteinsson, MD, Department of Psychiatry, University of Rochester School of Medicine. Dr. Porsteinsson is the Director of the University of Rochester Alzheimer’s Disease Care, Research and Education Program and has devoted his career to the care and study of individuals with memory disorders. Following up on his recent randomized clinical trial of citalopram, we discussed why it’s important to focus on treatments for AD-related agitation — both for AD patients and their caregivers.
Real World Health Care: Why is it important to study agitation in patients with Alzheimer’s disease?
Anton Porsteinsson: Agitation is quite common in people with AD. It has a huge impact on their quality of life, as well as their family members’ and caregivers’ quality of life.
RWHC: Prior to your CitAD Randomized Clinical Trial, why had previous pharmacological treatment options been deemed unsatisfactory?
AP: A number of medications have been studied over time for this condition, including atypical and conventional anti-psychotics and mood stabilizers. But the efficacy they showed, if any, was modest at best. At the same time, these medications have serious potential complications such as increases in cerebrovascular events, sedation, falls, Parkinsonism and even increased mortality.
RWHC: Your trial focused on patients receiving psychosocial intervention. Why is psychosocial intervention important for AD patients?
AP: Medications should rarely be the first line of treatment for AD patients. Not everyone needs to be treated with medications. That’s why it’s important to evaluate the root cause of the agitation problem. Is the patient agitated because of something going on in his or her environment? I remember a situation from a few years ago when I was seeing a summertime spike in agitation-related consultations from patients in a particular nursing home. It turns out the nursing home didn’t have air conditioning. So it’s not surprising patients were bothered and agitated. In AD cases, agitation may have as much to do with your roommate as your receptors.
Psychosocial intervention helps to channel nervous energy and restlessness by involving patients in something purposeful, or even giving them some sort of outlet, like an area to pace around where they are safe and not in anyone’s way.
RWHC: The trial also focused on the effects of citalopram on caregiver distress. Why is this an important area of study?
AP: Caregivers, who are often family members with little or no medical training, may not understand what is going on with their loved one. They may take the patient’s behavior personally, which can cause a great deal of stress. Even if you’re a saint, it can build up and take a lot out of you.
Providing care for someone with AD is very hard under the best of circumstances. It’s even more difficult when the patient is verbally or physically aggressive, uncooperative, or agitated. Caregivers need advice, support and tools to help them handle the situation. They need to learn to give themselves breaks, that it’s OK not to be perfect, and that help is available for them. I find that a lot of caregiver stress is alleviated when, as health care providers, we listen to them and take their concerns seriously.
Caregivers need to know that agitation in AD patients is common and that there are ways to deal with it. Providers must connect them with resources like the Alzheimer’s Association and community agencies. We need to help alleviate their concerns about finances. And we need to help them set up a working plan on how to deal with their situation — to bring order to the chaos.
RWHC: How will the results of the CitAD Randomized Clinical Trial inform your future AD research?
AP: This trial was extremely educational for the research community. It was one of the first studies to show that a medication was effective in multiple ways — both on a clinical scale in reducing agitation among patients and in reducing caregiver distress. We also found efficacy for other AD patient behaviors like anxiety, irritability and delusions or hallucinations.
On the flip side, we discovered some complications. Citalopram has been used widely for decades with vulnerable populations. But in the last five or six years, it’s been found to not be as safe as once thought. It has the traditional SSRI side-effects of mild gastrointestinal distress and mild sleep pattern disturbances. But it also has been found to have an impact on cardiac conduction, especially in higher doses. In fact, when we were about three-quarters of the way through the study, the FDA suggested that, for people older than 60, there should be a dose limit of 20mg per day.
We confirmed this finding in our study. We also saw a drug placebo difference on a cognitive measure, the MMSE (Mini Mental State Examination). It isn’t clear if this was due to baseline differences between the two groups and drift toward the mean, as the placebo group improved on the MMSE and the drug group saw a modest decline, or if it was a true modest cognitive toxicity. Until proven otherwise, we have opted to assume this is a potential side effect and we warn against it.
For our next study, we considered testing a lower dose of citalopram (20mg daily), but then we found that the active isomer of citalopram (S-citalopram) seemed to be better correlated to benefits seen in the study, while the inactive isomer (R-citalopram) more correlated with the adverse effects. S-citalopram is available as a generic drug, approved for depression and anxiety. We intend to study that drug further.
RWHC: What are some other areas of AD research you’re currently involved in within the URMC Memory Care Program? What do you see as your most promising area of research?
AP: We have a broad portfolio of research programs at URMC. We’re one of the more active academic-based clinical research programs in the country. Currently, we’re conducting two behavior-focused studies. One is ongoing and is based on positive findings on dextromethorphan hydrobromide and quinidine sulfate, with a new formulation that uses less quinidine. We’re also looking at methylphenidate for treatment of apathy in patients with AD.
We’re also investigating new imaging techniques and various biomarkers to improve our ability to identify those at risk. And, we’re working to find better ways of monitoring the progression of the disease and response to treatment through the ADNI study, which just received a fourth wave of funding.
Other areas we’re investigating include prevention studies with people who are cognitively normal, but who have elevated beta-amyloid or genetic biosignatures that indicate future pre-disposition. We’re looking at a passive and active vaccine against amyloid production. And we have a number of different studies on the prodromal stage of AD, working with beta secretase inhibitors that block the production of beta-amyloid.
It’s actually a very exciting time in Alzheimer’s disease research. We’re seeing improved funding from federal sources and a rejuvenation of interest from the pharmaceutical industry. I’m quite optimistic that in the next five to ten years, we will make substantive progress in terms of our ability to limit AD. I think it’s overly optimistic to expect a cure in that timeframe, but we can certainly make a dent, particularly from an early intervention standpoint. Treating this disease early is the critical factor.