All right, hi everybody. My name is Dr. Christina Denise, I'm a geriatric psychiatrist and chief of geriatric psychiatry at the University of Connecticut. Really glad to be here this morning and have you joining us in this geriatric series. My topic today is going to be depressive disorders in older adults. I don't have any conflicts of interest to disclose for this presentation. I do have one slide that discusses off-label use of medications, and I'll make note of this clearly when we're going through the talk. My objectives for you today are first to be able to describe the epidemiology of depressive symptoms in older adults. I hope that you'll be able to distinguish major depressive disorder from other depressive presentations in older adults. I want you to understand the relationship between depression and cognitive disorders in older adults, which is a big theme in geriatric psychiatry. And I also want you to be able to identify treatments for depressive disorders in older adults. When thinking about the epidemiology of late-life depression, or what I will abbreviate as LLD, it's really hard to describe because late-life depression is a heterogeneous condition. Factors that might impact the particular epidemiology or prevalence within a particular group could include what the type of depression is, what the symptom presentation is like, whether the adult is community dwelling or in a nursing facility or in some other living environment, what the individual's comorbid medical illnesses are, what's their level of frailty and their functional ability, what are their sociodemographics, and also within the older adult population, what is their age because the cohort of 65 to 75 in many ways is different than the cohorts between 85 and 95. Major depressive disorder comes to mind first when we talk about depression. We'll elaborate on it more, but I think many of you are familiar with MDD. Estimates for older adults range from about 1% to 5% among community-dwelling older adults. As I said, the setting in which the rates are determined can impact that percentage. Among older patients who are hospitalized in medical units, the rate of major depressive disorder is up to 21%. We'll talk about in coming slides how somebody's medical illnesses might impact their risk of developing depression and how depression might impact their medical illnesses. If you look at patients living in skilled nursing facilities, over 25% meet criteria for major depressive disorder. Maybe that number is surprising to you because it's so high, or for some of you, maybe that number seems a bit low, but remember, to have a diagnosis of major depressive disorder, you have to meet very specific criteria, which we'll go over today. Among people in skilled nursing facilities meeting that criteria, we see that in over a quarter of them. Depressive symptoms are much more common than major depressive disorder. If you look at community-dwelling older adults, about 27% are going to have some degree of depressive symptoms that impact their daily routine and their functioning and their quality of life. If you look among hospitalized older patients, this is that same cohort on medical units, over 40% of those patients have some degree of depressive symptoms. It's important not to ignore depressive symptoms just because they don't meet criteria for major depressive disorder, because the impact can still be significant. There are many different risk factors that can contribute to somebody's risk of late-life depression as well. Among biological risk factors, some things that we'll consider are genetics and neurotransmitter dysfunction. This may be related, for example, to the serotonin transporter gene and serotonergic transmission. Male gender, women are much more likely to experience late-life depression. Endocrine changes, for example, if somebody has a long-standing elevated cortisol, that puts them at higher risk. Vascular changes are very important to consider, and I'll devote a slide to talking about vascular depression as a construct. Medical illness, we'll elaborate on different types of medical illness and risk of developing late-life depression. I'll elaborate also on neurodegenerative illness and cognitive disorders and their complicated relationship. That's one of the objectives I'm hoping you are able to take away from this lecture today. Inflammation can contribute to late-life depression, and comorbid psychiatric disorders such as anxiety also put people at higher risk. Among psychological and social risk factors, personality attributes can contribute to late-life depression risk, so people who tend towards hopelessness or ambivalence are at higher risk. A major personality construct that's been studied in relationship with late-life depression is neuroticism. Folks who have high levels of neuroticism on personality scales are found to have a higher risk of late-life depression and difficulty responding to depression treatment. I'll elaborate on that in a little bit as well. Psychologically people who tend toward cognitive distortions such as feelings of abandonment or feeling like the glass is half empty are at higher risk of developing depression. Social origins are very important to consider somebody's ethnicity, culture, family background. Stressful life events can trigger late-life depression, for example, the death of a close friend. A change of residence often may happen in later life. Early life stressors and chronic stressors can also put them at higher risk, and low socioeconomic status has been associated with late-life depression as well. Let's take a minute to elaborate on those vascular risk factors. Late-life depression has been associated with hypertension and stroke in our patients. It's also associated with white matter changes and other changes on MRI. White matter hyperintensities, cerebral small vessel disease, microbleeds have been associated with late-life depression, leukoencephalopathy, lacunar infarcts. The thought, for example, with the white matter hyperintensities is that the mechanism is such that the white matter hyperintensities are disrupting neural circuits and networks. This is important prognostically because the more we see increasing white matter hyperintensities, the more we see an association with poor long-term depression outcomes and worse response to treatment. Vascular depression as a concept may be a distinct diagnostic entity. It's not yet recognized by the DSM as its own form of depression, but it's very important because it can be more difficult to treat vascular depression than other types of major depression without the vascular involvement. I think this is especially important because vascular depression could be a link between cognitive decline and depression, because vascular changes in the brain can certainly contribute to both. Let me elaborate a little bit on the relationship with medical illnesses. Associated with increased frequency of late-life depression are myocardial infarction, diabetes, hip fracture, stroke, arthritis, urinary and bowel incontinence, chronic pain, and Parkinson's disease. The list is not exhaustive, but those are some very common medical conditions that we see associated with increased risk of late-life depression. Among older adult patients, we often see a combination of multiple medical illnesses that you may see in this category. I think this is important also because you can see these are not all strictly brain diseases. Cardiovascular disease, medical illnesses that are impacting somebody's functional ability, that contribute to pain, that contribute to their inability to care for themselves. All of that is really important, and you can imagine that with a combination of medical illnesses, we're going to see spikes in the rate of late-life depression. What's important about understanding the relationship between medical illness and late-life depression is that that relationship can really be bidirectional. Medical illness, any of these may physiologically predispose to development of depression. Developing the medical illness may cause an adjustment reaction with depressed symptoms. We have medical illness first leading to depression, but we also know that depressive symptoms may worsen medical outcomes. People who have depression tend to do worse prognostically when they have these comorbid medical symptoms. In talking about psychiatric comorbidity, I will note that comorbidity for older adult depression is less frequent than in earlier life. Younger adults tend to have more psychiatric comorbidity than older adults with depression. However, there are associations that are very strong, including associations between depression and anxiety, depression and insomnia, depression and alcohol use, and depression and cannabis use. I want to underscore that for our older adult population, it is really important to be scanning for illicit substance use, especially cannabis. The baby boomer generation grew up, many of them in the 1960s, and this was part of their early adolescence. For many, they are continuing to use cannabis these days. Don't forget to screen for that. Here is an important concept that I really want to underscore in today's talk. That is the relationship between neurodegenerative illness, dementia, and depression. This is a very complicated relationship and could be a whole talk unto itself. For purposes today, I will touch on some key points, and then if you want to elaborate during the Q&A, we certainly can do that. What we know is that depression is likely both a risk factor and a prodrome for dementia and Alzheimer's disease. What is the difference between a risk factor and a prodrome? A risk factor would be that the patient has had episodes of depression in the past. A prodrome for dementia would be that the depressive episode is immediately preceding the onset of cognitive symptoms. This is especially true for Alzheimer's disease. It is also associated with all-cause dementia. Among patients with Alzheimer's, we see depressive symptoms preceding the onset in 10% to 15% of cases. We know that the risk for Alzheimer's increases with the number of historical depressive episodes. It's like depression is toxic to the brain. There may be a relationship also pathophysiologically. Some possible pathophysiological mechanisms could include that amyloid deposition also predisposes to depression. We know that amyloid gets deposited well before the onset of cognitive symptoms, and that depression preceding the Alzheimer's could be a manifestation of that pathophysiological change. We know that there's abnormalities in nerve growth factors that can contribute to depression. We know that glucocorticoid system abnormalities could also contribute. I mentioned inflammation before. There's also pro-inflammatory processes that are happening in the early stages and throughout the course of Alzheimer's and other types of dementia, which may be associated with the mood change as well. To elaborate a little bit on neuroticism. For those of you who might be less familiar with the construct of neuroticism, it's not an official personality disorder, but it's a personality construct in which patients have high levels of negative affect in response to minor stressors. They tend to react disproportionately to challenges they face in their life. They are focusing on the adversity that is facing them rather on their self-efficacy and resilience. As a consequence, they tend to also have poor coping skills. They lean towards maladaptive cognitive distortions. This would be very much a glass is half empty outlook. We know that neuroticism is associated with the development of late-life depression symptoms, a poor response to antidepressant treatment, and also poor cognitive outcomes among depressed older adults. Here at the University of Connecticut, we do a lot of work on neuroticism in late life. I'd be happy to elaborate on that during the Q&A at the end as well. Let's talk about some social stressors that we commonly see among our older adults in later life. These could be acute or they could be chronic. Acute social stressors could include bereavement, for example, the loss of a close contact. It could be related to housing or a change in residence. I work at assisted living facilities. A lot of the people I see there are adjusting to being in an apartment in a community setting of being part of sharing dining room time with other people and sharing activities and transportation with other people when previously maybe they were living in the same house for 40, 50, even 60 years in some cases. Social stressors can include new severe illness, and that could be in the individual themselves or it could be in somebody they care about very much, and that can cause a late life depressive episode. A change in their role, for example, somebody who has been working their whole life and is facing retirement, we often see that as an acute trigger for the development of late life depression. Chronic social stressors contributing to late life depression could include lower socioeconomic status, a lack of social support, and caregiver burnout as well. Caregiver burnout is another topic that could be its whole hour-long talk, but recognizing that the older adults who are caring for our patients themselves could be experiencing depression in the context of that stressor. Now the risk of depression is going to increase with the severity and number of stressful events, so there could be a combination of caregiver burnout and dealing with the care recipient's severe illness, for example, or bereavement. Let's switch gears a little bit and talk about the differential diagnosis of late life depression. So as I mentioned, late life depression is very heterogeneous. It can fall into one of many categories. I'm going to talk about each one of these today. Major depressive disorder being the one I think we're most familiar with, but we're also going to talk about major depressive disorder with psychotic features or something called psychotic depression. We'll talk about bipolar disorders a little bit. I know it's covered elsewhere in this series. Dysthymia, subsyndromal depression, which is similar to dysthymia but slightly distinctive, so we'll underscore that distinction. Depressive disorder due to another medical condition, substance or medication-induced depressive disorders. We'll talk about adjustment disorder with depressed mood and then bereavement as well. So major depressive disorder, MDD, you're probably familiar with the DSM criteria, but as a quick review, there are two or more weeks of symptoms. One has to be one of two core symptoms, so that could be depressed mood or loss of interest or synedonia, and then associated with that, we have four or more of a change in appetite or weight loss, sleep disturbance, a loss of energy, fatigue, feelings of worthlessness or guilt, poor concentration is common in this population, as well as suicidal ideation. And there's many modifiers for major depressive disorder. Anxious distress is one of them. We can also see patients who have melancholic features. They could have mixed features among these different categories or atypical features. We could see a seasonal pattern as we're going into fall, for example. We're seeing an uptick with the light changing and the weather getting colder. Catatonia and psychotic features obviously being the most severe forms. So when we talk about psychotic depression or major depressive disorder with psychotic features, I want to emphasize that there's a very high prevalence over the age of 60. To have a diagnosis of psychotic depression, delusions or hallucinations must be present. And the psychosis could either be mood congruent or it could be mood incongruent. So somebody who has a psychotic depression with mood congruent features, those psychotic symptoms are going to have depressive content. So that could be feelings of guilt that are highly disproportionate to the actual, what they perceive as a misdeed. So for example, maybe somebody had dinner with someone 30 years ago, and they have blown it up to feeling guilty as though they had cheated on their spouse and had an affair or deserved punishment. I must have done something terrible to deserve to feel this way. Or symptoms of disease. We'll elaborate a little bit on this too, but oftentimes themes ranging from having an incurable illness or having, there's oftentimes a terrible problem that nobody is diagnosing. They're missing some horrible gastrointestinal illness or they're missing a problem with my heart, something like that. Mood incongruent would be psychotic features that don't include those depressive themes. So again, to elaborate, typical presentation in older adults, incurable illness, somatic symptoms with a focus on the abdomen, gills about past indiscretions. We see less frequent hallucinations, more frequent delusions in older adults with psychotic depression. It's often accompanied by psychomotor retardation, and we do see a higher risk of suicidal ideation in this category as well. Bipolar and related disorders are covered elsewhere in this series, so I'm not going to elaborate on them very much, but just some key points. If you have an older adult who's presenting with depressive symptoms, look for a previously undiagnosed bipolar history before you treat them. Diagnosis of bipolar disorder was much less common several decades back and oftentimes was dismissed as somebody who's just kind of high-flying at times. We would see people who are highly productive in their work environment who could work for days without sleeping. That was regarded not as a psychiatric illness but as an asset. So it's really important to dig a little bit deeper and look for symptoms that could have been consistent with mania in the past. And another key point, older adults who have bipolar disorder often present more with depressive symptoms rather than a manic presentation or a mixed presentation. So it's important to have your ears open and to be looking for clues regarding a possible bipolar diagnosis. In terms of dysthymia, this is also called persistent depressive disorder. These are persistent and significant symptoms that are often associated with chronic psychosocial stressors. Diagnostic criteria for dysthymia may include or do include symptoms for over two years, more days than not. And the symptoms can't be absent for more than a two-month stretch. So very persistent. And they're characterized also by a depressed mood for most of the day plus two additional symptoms. You might consider this a lower grade than a major depressive disorder but certainly more persistent. The symptoms are similar to major depressive disorder, could include appetite change, sleep change, low energy, low self-esteem, poor concentration, feelings of hopelessness. So this can be really unrelenting. And because it's so unrelenting, it can be very impactful on our older adults functioning. The presentation of dysthymia in older adults in some ways may be different than we see in younger adults. Among older adults, we see lower rates of a psychiatric family history and lower rates of comorbid personality disorders, things that we would be looking for more in the younger cohort. Often, the dysthymia is triggered by social stressors. We do see the relationship with cerebrovascular disease and neurodegenerative pathology ringing true for dysthymia as well. So it's important to consider those aspects. Antidepressant medications may help but don't always have as high efficacy for older adults with dysthymia relative to treating someone with, for example, a major depressive disorder. I think subsyndromal depression sometimes gets blurred with dysthymia. So it's similar to both dysthymia and major depressive disorder. So they don't meet full DSM-5 criteria for major depressive disorder, but it's a two-week duration, not a two-year duration, in which they have a depressed affect and one other major depressive symptom for at least two weeks. The impact can still be severe for patients at the subsyndromal level. It impairs their physical functioning. They have greater rates of disability. They have poorer self-rated health, meaning when they look at their medical conditions relative to somebody who doesn't have subsyndromal depression, they're going to be rating it lower. They also perceive that they lack social support, whether or not that's actually the reality. Let's talk about adjustment disorder with depressed mood. Our older adults are facing a lot of changes in their lives. They're facing a lot of stressors. An adjustment disorder with depressed mood is related to an identifiable stressor for which the depressive symptoms occur within three months. So there's going to be a clear association of the onset of symptoms with the stressful event. Those events could include family or social stress, a loss of their social role. Maybe their kids are grown up and they feel like they're more a spectator now than an active parent. Maybe they are going through retirement and their whole structure of their life is changing. They have a change of residence, as I mentioned before. You can have some overlap of adjustment disorder with depression due to a medical illness. The one thing I will note, we're going to talk about bereavement in a minute. Bereavement is an exclusion for adjustment disorder with depressed mood. So for bereavement, we also refer to this as a grief reaction. Typically, this is associated with the death of a significant close contact. So that might be a spouse, a sibling, an adult child. In some cases, it might also be a parent for our older adults who also have older parents. It's not just related to the actual death. There can be a pre-death grieving period. We see this a lot for people caring for loved ones who have dementia, for example, where they know their loved one doesn't seem to be the same person. The person they married isn't there anymore, but they're still caring for the individual and they're anticipating that the individual is going to die. So there's a whole grieving process associated with that. That ambiguous loss can be extremely challenging. It doesn't necessarily have to be bereavement related to someone else. An individual can have a grief reaction to decline in their own health. For some of our older adults who don't look like they did when they were 35 years old, there might be a change in what they perceive as their attractiveness or their capabilities, and that can be a grieving process. And I think in grief, it's important to recognize that there's two parallel processes. So on one hand, the individual who's grieving is adapting to the loss of the presence of their loved one. And this can be post-death or it can be pre-death with that ambiguous loss. So they're trying to get used to it. And simultaneously, they're trying to build a new life without the loved one. So there's like a deconstruction and a reconstruction that are happening at the same time. So this is a very challenging psychological process for somebody to be going through. And bereavement can occur with a depressive episode. I think this is important to recognize. Back when I was in training, bereavement was considered an exclusion for major depression. So they felt in those days that major depression, if somebody was grieving, then by definition, they couldn't be undergoing a depressive episode. But now we know that you can be going through both. You can be going through a grief reaction and meet criteria for major depression, and it should be treated as such. So let's compare grief with depression, because sometimes this can be a little bit unclear. For somebody who's grieving, typically, those feelings of low mood and sadness will come in waves. So they'll feel okay, and then they feel really down, and then they feel better, and then they feel really down. But in depression, it's a persistent low mood. So you're not going to have those moments of euthymia in between. There's capacity for joy and humor in people who are grieving. So if you've ever been to a funeral, perhaps you've noticed that during the eulogy, sometimes people will tell jokes or recount funny situations in which the person who's deceased was a participant, and people will laugh, and they will celebrate the life joyfully. Somebody who is depressed does not have the capacity to feel joyful or lighthearted in that same way. They are weighed down by the depression. People who are grieving recognize a feeling of emptiness. There's a loss. There is a hole left in them when the person passed away. The feeling of emptiness is not the same as feelings of guilt. So we do see people who are grieving express some feelings of guilt, like, oh, I wonder if I had brought them to the doctor when they first started losing weight. Maybe they would have picked up on the cancer diagnosis earlier. So there's questions like that surrounding the individual's diagnosis. But for people who are depressed, those feelings of guilt can often be quite severe and debilitating. And psychotic depression, as we mentioned, can even have a delusional quality to them. When people are grieving, depending on their belief system, sometimes they might express that they are looking forward to their own death because they feel they will be reunited with their loved one. It's something to look forward to. But looking forward to death does not mean that they are suicidal or planning to take their own life. In fact, in many belief systems, they worry that if they did take their own life, they would not be reunited with their loved one. So that type of reflection is much different than suicidal thoughts, thoughts that they would be better off dead, thoughts of self harm that we see in a depressive episode. Late-life depression has many consequences. So older depressive adults, older depressed adults have greater chronicity, longer time to remission, and greater depression severity. We see late-life depression associated with cognitive impairment, with more medical comorbidity, as I highlighted earlier, suicide we're going to elaborate on, and mortality. So mortality not related to suicide, but in terms of life expectancy related to medical conditions among people who have late-life depression. Suicide is a major concern in caring for older adults who have depressive symptoms. So adults over the age of 70 have the highest risk of suicide. And this actually breaks down very clearly by gender. So among older males, among all males, the highest rate of suicide is for those men over the age of 75. This is a pretty high rate, almost 40 per a hundred thousand. Among women, the highest risk of suicide is actually in the 45 to 64 year old cohort. And the risk does decline after 75 to the point that that older women group is the lowest risk among women, except for teenage girls. There's some evidence among people who have been diagnosed with dementia, that there is a higher rate of suicide. Among older adults who have depression, passive suicidal ideation is expressed in anywhere from 25 to 60%, depending on other factors. Suicidal behavior in older adults is more likely to result in death than suicidal behavior among younger adults. Part of this might be that older adults are less likely to report suicidal ideation. So we're not picking up on it as early. They're less likely to seek mental health care, and they're also more likely to use lethal methods for suicide. Briefly to touch again on that non-suicide mortality risk, the relative risk of mortality is 50% higher for older adults who are depressed versus those who are non-depressed. That mortality risk is predicted by severity and duration of depressive symptoms. And apathy is a specific symptom that may be related to mortality. I want to touch on apathy briefly. Apathy is distinct from depression, and it's also different from anhedonia. I think a lot of times we mix anhedonia and apathy. But apathy, to define it, is characterized by diminished initiative, diminished interest, but it's also related to a lack of emotional expression and decreased responsiveness, which is not classic for an anhedonia picture. We see apathy associated with cognitive and functional decline and dementia. It's also associated with executive function impairment. And it's important to recognize because it does have a limited treatment response to antidepressants. So it's important for us to think about the big picture of how we might be helping these patients going forward. This is another topic I'm not going to linger on too much in this talk, but we can certainly talk about it in more detail during the Q&A. Let's switch gears and talk about the workup for late-life depression. So clinical screening, you can pick your screening questionnaire of choice. We often use the PHQ-9 for older adults as well as younger adults. But I wanted to throw out there the geriatric depression scale as well can be useful. What I like about the geriatric depression scale is rather than having the patient rate their severity as never a few days a week, most days per week, all the time, rather than having to figure that out for each depressive symptom, it's a yes or no. Which I think, especially for older adults who may be having some degree of cognitive impairment, it can be a little bit more accessible. So I would certainly encourage a clinical screening as part of the workup. History of present illness is really important. Some highlights I would include would be onset. Has this been abrupt? Has it been correlated with a specific stressor or a medical diagnosis or the death of somebody close? What is the time course and the pattern? Is this a persistent low mood? Is it waxing and waning the same way that a grieving picture might look? Going through the symptoms is really important as targeting specific symptoms may guide you in your choice of antidepressants. We'll talk about treatment a little bit later. We want to talk about the impact on the individual's functioning. So not just are they engaging in activities, but is this impacting their ability to care for themselves in terms of, for example, personal hygiene or taking their medications? A suicide and safety screening is critical, as we discussed with the suicide risk. Knowing what the exacerbating and mitigating factors are and acute stressors is really important to think about the psychosocial picture. In all of psychiatry, it's very useful to have collateral informants. I think specifically with older adults who either might not have been raised in a psychologically minded context, who might not have the words to describe how they're feeling in a psychological way. I think it's important to get somebody else's input on how they're doing. And also for patients who may be experiencing some degree of cognitive impairment, they may lack insight into their symptoms. So hearing from somebody else's is critical. We of course want to do a full interview, including their prior psychiatric history. Have they had prior depressive episodes? When did those start? What did those look like? Were they hospitalized? Is there a history of suicidal ideation? What treatments worked? What treatments didn't work? Medical history is critical. Again, we've been emphasizing the relationship between medical illness and development of late life depression. Substance use, again, relevant in the older adult population. Understanding their family history, who has had depression? What has that looked like? What treatments have they responded to? Also understanding a family history of dementia is critical because we want to look at that relationship between the depression and possible onset of dementia symptoms. Social history, I think I've talked your ear off regarding those acute stressors and supports. As part of the mental status exam, it's important to be screening for cognitive impairment. I tell all my residents, if you have an older adult coming in with depressive symptoms, you are paying attention to see what's going on in terms of their cognition because this could be a warning sign that there's something cooking. The physical examination is also important, especially in older adults because you want to be sure that you're not missing another physical component or medical component that could be contributing to the symptoms. Identifying what the modifying factors are, the protective factors are, is going to guide your treatment planning. Knowing who the patient has for social supports and what social supports might be lacking. Understanding their broader context, things like religious involvement can be very helpful in terms of working with people with depression of all ages. What other community groups or organizations might they be a part of to give them purpose in their day-to-day life? Understanding what may help them engage in treatment. Is this somebody who's going to do really well in a group therapy setting or is this somebody who is going to shut down in a group therapy setting, for example? Certainly, identifying risk factors. What is this person looking like in terms of social isolation? Do they have access to firearms or other suicide methods? What is their substance use, for example? Among our laboratory studies, certainly looking for vitamin deficiencies such as B12 and vitamin D can be relevant. Understanding their thyroid levels, understanding their CBC and their chemistries as either anemia or electrolyte abnormalities can be masquerading as depressive symptoms, as a change in energy level, a change in appetite, a change in engagement. Polysomnography is not a laboratory study per se, but I think it is a critical part of the workup for many of our patients. Undiagnosed sleep apnea is very common. It's not something that people automatically report to their primary care doctor if they're snoring, for example. People who are not sleeping well at night who have undiagnosed sleep apnea, and people who are not sleeping well at night who have undiagnosed sleep apnea or aren't using a CPAP, they may be presenting as low energy, not engaging, maybe having poor concentration, and that can masquerade as a depressive episode. This is also important to pay attention to if you have patients who are not responding to traditional antidepressant treatment, because this is critical that their sleep apnea is being addressed. In terms of talking about treatments, let's start with non-pharmacological treatments. Psychotherapy has shown comparable efficacy to antidepressant treatments for our older adult population, and these are several types of psychotherapy that I'd like to elaborate on for you today. We'll start with cognitive behavioral therapy or CBT. CBT is a form of psychotherapy with the goal to change the patient's behavior via their thinking, via their thoughts. CBT has demonstrated efficacy in older adults in multiple studies, effect sizes ranging from about 0.7 to 1.34. We know that CBT is effective in patients who have medical illnesses. It's less clear for patients who have cognitive impairment because there is a learning process associated with CBT. Patients need to be able to carry what they learn in one session and apply it going forward. If they're not retaining those skills, it's going to be hard to see improvement for CBT. That said, for people with more mild stage, mild cognitive impairment, they may still be able to engage in CBT. Another benefit is that CBT tends to be time-limited, so rather than engaging in a many-year psychodynamic psychotherapy, this is much more focused and goal-directed and can often be accomplished within 10 to 12 sessions even. Interpersonal therapy is derived from psychodynamic theory. It focuses on the individual's interpersonal relationships, but it's a bit more structured. It also involves psychoeducation, goal-setting, and identifying specific interpersonal challenges to be working on. Some examples of interpersonal challenges could include grief and loss, role transition, very commonly we see familial conflict addressed through interpersonal therapy. For older adults, there's less evidence for use of interpersonal therapy relative to CBT, but that doesn't mean that it's less effective. It just means that it's been studied less, so it could be very useful, and there's also evidence that interpersonal therapy can have benefit to reduce suicidal ideation. Problem-solving therapy, well accepted by older adults. Problem-solving therapy focuses on identifying a specific problem that could be compromising somebody's well-being, so there's a specific method to approach and solve those problems. This one is also time-limited, and the evidence for benefit is there in the older adult population, including those who have medical illness and who have mild dementia. Again, more moderate stages, they may not be able to retain what they're learning and apply it going forward. When you look at older adults in problem-solving therapy versus younger adults, there's some evidence that problem-solving therapy is actually better for the older adult population. Among medically ill older adults, there's some evidence that problem-solving therapy is more effective than supportive therapy and even more effective than CBT for the medically ill older adult population. This is something definitely to be considered when you're doing your treatment planning. Many of you are probably familiar with CBT and probably IPT and PST as well. I want to mention the ENGAGE program. This is probably less familiar to you. This is from Dr. Alexopoulos and colleagues. The ENGAGE program is a structured, step-wise, personalized treatment that focuses on reward exposure, but it's kind of a neurobiological retraining of the reward system. I'm not an expert in this by any means in terms of my own clinical practice, but I'm familiar with it enough to understand that basically, by focusing on barriers to the reward exposure, whether that is apathy or a negativity bias or emotional dysregulation, it's retraining the reward system. By doing that and overcoming those barriers, there's some improvement in depressive symptoms and also in behavioral activation. That's important when thinking about apathy, for example. Older adults tend to get more engaged, hence the name, in activities when they're going through this program. If you look at the efficacy, it's actually comparable to problem-solving therapy. This is something to have on your radar because it can be very useful and hopefully more and more therapists will be trained in the ENGAGE program going forward. Pharmacological treatments are also a really important part of our toolkit. You don't need to shy away from pharmacological treatment just because somebody's older. We know that antidepressant treatment is effective for late-life depression, period. There's no question about that. We know that basically, all antidepressants that work for younger adult depression potentially will work for our older adults. In the pharmacological treatment of late-life depression, there's some clinical challenges that we may see. Patients may say that their pharmacological treatment isn't working because perhaps they're getting inadequate treatment. We always say start low and go slow, but sometimes various clinicians may say, oh, I don't want to push you to a higher dose. They may need a higher dose and they may tolerate a higher dose. You do have to try if they're not getting the benefit you expect on the lower dose. I think too often, the treatment duration is also too brief. Maybe we're just trying a medication for three or four weeks without really getting it to a therapeutic dose for a therapeutic duration of trial. In some cases, unfortunately, I think with older adults, there's a lack of treatment entirely. Part of this may be related to detection and diagnosis. Some of it might also be related to a tendency to avoid giving more medications to patients who might have polypharmacy. But only about a third of older adults with late life depression are receiving antidepressant treatment. And that's not necessarily a good thing. Obviously, non-pharmacological approaches are great, but we wanna make sure that our older adults are having their symptoms met. General philosophy of prescribing strategy in older adults. This is probably similar to what you're hearing in other talks today. Yes, we are starting at lower dosages for older adults. So what you would start a younger adult on, often I split that dose in half even and put older adults on that first. But the idea again is to titrate it to a higher dosage and to a point of efficacy as they're able to tolerate. So it might be a regular younger adult dose that our patients are maintained on if they're tolerating it. So let's say start low and go slow, but keep on going. Don't shy away if the treatment is moving along. I think it's important to consider the side effect profiles of different medications in the context of their medical illnesses. So think about what their medical illnesses are, how those present in terms of their symptomatology and make sure you're not exacerbating those symptoms by side effects of our medications. And another big question in psychiatry is always, are we gonna augment our treatment or are we going to switch medications? And there's not always a right or wrong answer, but what I will say is for older adults, we do want to avoid polypharmacy. They're gonna be on a lot more medications than younger adults in most cases. So when thinking about adding on additional medication versus switching medication, oftentimes the switch makes more sense, at least initially, and especially if they're not having a partial response. So first-line treatment in general, I would say is an SSRI for older adults. These medications are very effective. In general, their side effect profiles are pretty mild. They don't tend to be anticholinergic. In most cases, they have limited cardiac effects. Typically, older adults don't get tired on them. There's a lack of sedation. If they take extra doses, we know that for SSRIs, there is safety in overdose relative to other antidepressant medications. Their risk of orthostasis is lower. So there's still a risk of falls with SSRIs, but tends to be lower. They're not gonna have the blood pressure fluctuations. Some side effects we do have concern about are sleep disturbance, especially when older adults are taking the SSRIs at night. The dreams can get very vivid. We sometimes see headache and tremor in older adults on SSRIs. Gastrointestinal side effects, like we would see across the age spectrum, and hyponatremia as well. It's rare, but when it does occur, it can be severe, leading to inpatient medical hospitalization. And of course, that is a very risky diagnosis. So it's important to be keeping an eye on that as well. Among the SSRIs we could choose from, among geriatric psychiatrists, we tend to prefer escitalopram and sertraline. If an older adult has known poor medication adherence, we could consider fluoxetine because it has a longer half-life. So if they miss a dose here and there, it's probably less significant. And we try to avoid paroxetine in older adults. I know oftentimes people like paroxetine. It's very good for anxiety, but it does have anticholinergic effects, and that can make our older adults confused and dizzy. So we try to stay away from paroxetine and prioritize sertraline and escitalopram. I'm listing these categories as second-line treatments. You can also consider them first-line treatments in certain situations. So for an SNRI, with the available evidence, duloxetine and venlafaxine demonstrate efficacy for late-life depression. There's been less research into desvenlafaxine, but I know that it's becoming a favorite among geriatric psychiatrists as well. You may consider duloxetine first-line for patients who have chronic pain, for example, because it is indicated for people who are dealing with chronic pain. Mirtazapine, I love mirtazapine. It's an antidepressant for older adults. It's very useful for treatment of insomnia and for treatment of weight loss, which are two very common complaints in our older adult geriatric psych population. So sometimes I do use it first-line for those reasons. It also works really well as an augmentation for SSRIs and works great as an augmentation for SNRIs as well. And then bupropion, it can be very useful in an opposite sense. So it's very useful for anhedonia. It's very useful for patients who have poor concentration, who have low energy, and can also be a useful augmentation for SSRIs. Bupropion, also lowest risk of sexual side effects, which is still relevant in the older adult population. I think sometimes we don't think about that, but it is significant for a lot of our patients. Other antidepressants that could be effective would be tricyclic antidepressants and monoamine oxidase inhibitors. So for the TCAs, yes, they are effective. Yes, they work, but they certainly carry a higher risk of side effects. So QTC prolongation, orthostasis, dizziness. They have a huge interaction profile. I will add serotonin syndrome to this list. It could be helpful for melancholic major depressive disorder subtype, and they can also be helpful for chronic pain, but I would use these really in moderation. In most cases, my experience has been that the risk of TCA outweighs the benefit for older adults. And same for the MAOIs. Yes, they are effective, but they do have a high risk of interactions, side effects, serotonin syndrome. And I know this is up for debate in terms of how much you have to worry about the dietary restrictions, but that is there and can be sometimes difficult to manage for older adults. So yes, these work. Yes, we do use them sometimes, but very judiciously. In terms of off-label, this is my one off-label slide for you. Off-label augmenting agents that would be considered by geriatric psychiatrists. Sometimes we use stimulants, especially methylphenidate for older adults who are presenting with anhedonia, low energy and poor concentration. I will do a trial of bupropion first before trying methylphenidate, but it's not out of the realm of reason to try that. Lithium can be useful for augmentation in lower doses. The levels of lithium that you would need in older adults, much lower, like a sprinkle of lithium relative to what we would use in a younger adult population. There is some concern with lithium impacting cognition. Although it's neuroprotective, it can make older adults very foggy. So we're mindful of that. Buspirone, sometimes we do use as an augmenting agent in late life depression when there's a significant anxious component for our patients. Switching gears one more time, let's talk about neurostimulation. So ECT, electroconvulsive therapy is really the most effective form of treatment, better than medication, especially for older adults who have severely life depression. We know that people who are older actually have greater speed and greater likelihood of response relative to younger cohorts undergoing ECT. It's very effective for major depression with psychotic features. It's very effective for patients who have suicidal ideation. But there are some risks which we will outline on the next slide. So I would consider only after other modalities have been ineffective. And I will say ECT can potentially have fewer side effects than antidepressants for older adults, especially when we're worried about things like, sleepiness and QTC prolongation. Risk of ECT would include a risk of cardiac event, complications of anesthesia, and also worsening of memory impairment, especially around the time of the treatment. Another type of neurostimulation, transcranial magnetic stimulation. TMS is safe, it's well tolerated. It's a big time commitment. So typically our patients are going in five days a week and 40 minute sessions for four to six weeks. So it's a lot of sessions. Not all our older adults can drive themselves. So it becomes a bit of an organizational challenge. But that said, it's side effect profile certainly better than ECT. You don't have to go under general anesthesia. Unfortunately, so far the evidence for TMS, the evidence is not as robust as for ECT, especially for older adults who respond so well to ECT. A note specifically on psychotic depression treatment. So I mentioned it's effectively treated with ECT. It's effectively treated also in many patients with a combination of antidepressant and antipsychotic. Predictors that the patient will have a poor response to treatment include impaired insight, higher risk of suicidal thoughts and cerebrovascular risk factors also predict a poor response to the treatment of psychotic depression. When thinking about whether to continue the antidepressant and the antipsychotic longer term, at least initially following remission, the antidepressant and the antipsychotic should be continued as the withdrawal of the antipsychotic is associated with higher risk of relapse. It's just really important to be following the metabolic profile for these patients as they are at risk for hyperlipidemia, weight gain, diabetes, and so on. So just to summarize, and then I'm happy to engage in the Q&A here. Late-life depression is heterogeneous, but it's very common. Rates of late-life depression may be higher among those people who are medically hospitalized and those in skilled nursing facilities. The depression-dementia connection is really important and depression can be both a risk factor and a prodrome of dementia, whether it's Alzheimer's type or all cause. Depressive symptoms may not meet criteria for major depressive disorder, but they still may warrant treatment. So it's important not just to go down the MVD-DSM-5 checklist, but listen to what the symptoms are and how they're impacting our patients. And just in summary with the treatments, medication, psychotherapy, and ECT are all effective in the treatment of late-life depression. So work with your patients, learn their history, and reassure them that we can get them feeling better. I've got my references here. We'll run through those. It's been a lot of research in late-life depression, so lots of folks to acknowledge here. Okay, so I am available to address some of these Q&A. Okay, so there's quite a few questions. I'm going to start at the top of my list. I believe that would be the original. It looks like eight have been answered already. Okay, perfect. So I'm going to go down my open list here. And I'm just going to be mindful of your time as well, because I think we're dismissing for lunch after this. But we do have, I think, just a little bit of time. And folks at the APA, please cut me off if I need to be cut off. So in terms of talking about the causes of apathy, I think of apathy as much more neurobiological than psychological. So we do see higher rates in patients who have high rates of cerebrovascular disease, vascular dementia, other types of dementia, like Alzheimer's disease, and certainly frontotemporal dementia. We see higher prevalence of apathy. So that's how I think about it, as distinct from an anhedonia that might be more related to a major depressive episode. Can you talk more about interventions related to apathy? Great question. I'm happy to just briefly elaborate. So when I think about apathy, I think, first of all, non-pharmacological interventions, promoting behavioral activation is really important. So bringing patients out of the house into more structured environments, whether that is a senior center or other sort of day program where they really have a schedule of events to follow, that can be really useful. And taking the onus off of the caregiver and putting it into more of a structured program, I think can be really helpful. In terms of psychopharmacological intervention, this would be off-label, but sometimes we do use stimulants, such as methylphenidate, very low doses, maybe 5, 10 milligrams. And we also use bupropion among the more stimulating antidepressants. Preference for geriatric depression scale, 15 questions versus geriatric depression scale, 30 questions. I think by the time you hit 15 questions, that's enough questions. I think you get enough of a sense of how somebody's doing. I don't think you necessarily need to get into the nuances of the 30 question GDS. And I think it becomes tedious for our patients to go down a 30-point scale unless it's involved in research or whatnot. Okay, another apathy question. Okay, if an adult is doing well on higher doses of citalopram or escitalopram, would you preemptively decrease the dose with age due to concern for QTC prolongation risk? Not necessarily. I know the QTC prolongation risk has been kind of questioned from time to time with respect to citalopram and by extension escitalopram. Typically for a patient on citalopram, I'll just get an EKG once a year and see what their QTC is. If it's under 500, I typically keep going in terms of a risk benefit. Yeah, and in terms of the prolonged QTC with escitalopram, yeah, theoretically, because we worry about the citalopram, but in general, I think the evidence for that is not super convincing. For a patient on an antidepressant, should serum sodium be monitored on a routine basis? I try to get at least once a year. If they have a history of hyponatremia, I'll get it at baseline and then every three to six months typically. When we first start them, I may check it in like four to six weeks, but if it's stable, then three to six months. Thoughts on Trentilix for late-life depression or Vortioxetine given its reported evidence for cognitive improvement. Yes, there is some evidence that there's cognitive benefit and I like this for older adults. I am not prescribing it often for older adults because it is remaining expensive on most insurance panels at this point. So I don't necessarily think that the benefit that far surpasses other SSRIs and bupropion, but definitely a consideration that we think about. Another escitalopram question. Why is fluoxetine not included with sertraline and escitalopram as first line? That's because it tends to have more cytochrome P450 interactions with the other medications in the context of polypharmacy. So that's the big drawback. Sertraline and escitalopram are much cleaner in terms of interaction profile. Okay, didn't bupropion augmentation have the highest risk of falls in the optimum study? I don't remember that, but I think that underscores the importance of monitoring for falls. So every time a patient comes into our office, I'm going to be asking them, have you had any falls since our last visit? Absolutely. And I think the big picture is while we talk about benzodiazepines as being the medications that we tend to avoid in terms of risk of fall, we really need to consider that in the context of all our antidepressants. Urinary retention or overflow incontinence or other adverse side effects from mirtazapine in older adults with dementia. Yes, in some cases, but in general, I find mirtazapine to be well tolerated. Bigger than the urinary symptoms, I hear a lot of constipation on mirtazapine. We talked about vortioxetine. Deslin, the vaccine. Yes, I consider Deslin, the vaccine, a very good option in the SNRI category. Do medications used to treat comorbid dementia improve depressive symptoms without the addition of an antidepressant? For any behavioral symptoms in dementia, especially Alzheimer's type, but also potentially vascular in dementia with Lewy body, the addition of a cholinesterase inhibitor can be very helpful. I don't think it's as robust for treatment of depression as giving the patient an antidepressant. If the patient truly has debilitating depressive symptoms, I will go ahead and prescribe an SSRI or SNRI. Any concerns about using trazodone if used for sleep, specifically orthostasis and or cardiac issues? So I know colleagues in other specialties are really focused on trazodone and cardiac issues. I think it's the same as with other antidepressants. Just be mindful of their cardiac history, their EKGs, and in terms of the ortho, but in general, I don't let that stop me using trazodone. I'm going to start with a very low dose and the same with the orthostasis issue. I'm going to be starting a very low dose of trazodone, like 25 milligrams and monitoring how they're doing. Okay, we have a couple other, ooh, just keep getting, these are all excellent questions. So expand on the research about neuroticism. So neuroticism is a very interesting construct in older adults. It's related to the development of late-life depression. It's also related to the development of Alzheimer's and other types of dementia. So we know that people who have neuroticism are higher risk of developing dementia. So this goes back to that intersection of depression and dementia. I think about neuroticism as somebody who tends to be a little bit more rigid, who can't go with the flow. And as older adults progress through their later years, they're hitting more and more roadblocks. They're losing roles that they used to have. They're losing relationships they used to have. They are sometimes losing their self-confidence. They are sometimes being forced to make decisions based on what other people are telling them. It's really hard to go with the flow if you have high neuroticism. And I think that makes it much more difficult to respond to antidepressant treatments. So I think of neuroticism as kind of toxic to the brain in its relationship with the depression and the dementia. But yeah, that's another whole talk there, but those are just some highlights. TMS for treatment-resistant depression. I think it's reasonable to try. Again, the evidence for older adults is less clear at this point, but if you have an older adult who's struggling with late-life depression, they're not responding to psychotherapy and antidepressant treatments, if they can commit to the TMS schedule, the side effect profile is better than the ECT, even though we know that ECT is gonna have a robust response. So I would definitely consider it. Have I used stimulants or modafinil or Provigil as an agent against apathy? Yes. So absolutely, the use of stimulants would be appropriate. I think agents like Provigil, modafinil, a little bit less robust, but certainly in our bag of tricks off-label. And what is my take on ketamine use for treatment-resistant depression in older adults? I think that one is a to-be-continued. I think treatment-resistant depression needs to be adequately treated. And just like TMS or ECT, I think in some cases it is appropriate. But I think also understanding the side effect profile, cardiac risk, what the patient's medical history is, it really has to be on a case-by-case basis. Okay. I think I got all the questions. Thank you for your engagement today. This has been fun for me and I love the discussion. I'll see if there's anything else. Okay. I think we can wrap up now. So I hope everybody has a wonderful rest of the day. Thank you for participating and reach out if I can be of any further assistance.

geriatric psychiatry

depressive disorders

major depressive disorder

cognitive disorders

Alzheimer's disease

late-life depression

psychotherapy

pharmacological interventions

neurostimulation

treatment-resistant depression

individualized treatment