My name is Dr. Susan Lehman, and I'm delighted to be with you today as part of this course in updates in geriatric psychiatry. I will be speaking with you today about psychotic disorders in late life. I am the clinical director in the division of geriatric psychiatry and neuropsychiatry, as well as director of the Geriatric Psychiatry Fellowship and associate professor at the Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences. I do not have any conflicts of interest to disclose, but I do want to point out at the start of this talk that while there are no FDA approved medications for the treatment of behavioral and psychological symptoms of dementia, I will be talking about them. And therefore, all medications discussed today for the treatment of behavioral and psychological symptoms of dementia should be considered off-label in their use. So our objectives today for this talk are the following. I hope by the end of the talk that you will be able to identify the prevalence of psychotic symptoms among older adults, describe an appropriate workup for new onset psychosis in late life, distinguish between psychosis associated with the dementias and that associated with primary psychiatric illness, identify risks of using antipsychotics in older adults, discuss the approach for pharmacotherapy for schizophrenia in late life, and describe psychosocial as well as somatic treatments for schizophrenia in later life. When we consider the prevalence of psychotic symptoms in the elderly without dementia, you will see that they're not insignificant. And indeed, psychotic symptoms are present in about 10% of 85-year-olds, 7% of 95-year-olds, including hallucinations, delusions, and paranoid ideas. We also recognize that there is a significant incidence of very late-onset psychotic disorders, that is, in individuals beginning after the age of 65, which is not trivial. Among the affective psychoses, the rate is close to 31 for 100,000 person-years at risk and for schizophrenia, 7.5 for 100,000 person-years at risk. When considering the prevalence of psychotic symptoms among those individuals with dementia, again, these are significant as well. Psychotic symptoms are present in individuals with Alzheimer's disease, usually not as a presenting symptom of the condition, but very commonly in the middle stages and late stages of Alzheimer's disease. Up to 63% of people with Alzheimer's disease will experience delusions, up to 41% may experience hallucinations. And psychotic symptoms are among the hallmark features in dementia with Lewy bodies, as we will discuss a little bit later in the talk. Hallucinations have a prevalence rate of 78%, misidentification symptoms and experiences are up to 56%, and delusions also very common in 25% of individuals with dementia with Lewy bodies. So now let's address what would be the appropriate workup and consideration of differential diagnosis in an older adult who has psychotic symptoms. The diagnostic evaluation needs to be very comprehensive, thorough and thoughtful, as you would for any difficult symptom that you want to understand, beginning with a very comprehensive and good history from the patient. But you'll also want to obtain history from all significant others, people who know the patient well and can describe the symptom and its course, whether it's been present early in life and how the changes may differ from the pre-morbid personality of the individual. You'll want to take a comprehensive history of psychiatric illness that the patient may have had and obtain previous psychiatric records, if available. You'll want to pursue the family history of psychiatric illness, take a very careful history of alcohol and illicit drug use, do a thorough psychosocial assessment to determine who the patient lives with, who are their psychosocial supports, what has been their employment history, education history. You want to take a very thorough medical history and review of all medications, including over-the-counter medications that the patient may be taking, in addition to all prescription medications and dosages. You want to have consideration for a thorough physical and neurological examination and have laboratory evaluation, including a urine tox screen. For some individuals, neuroimaging, such as a brain MRI, may be appropriate. And where cognitive impairment is a concern, you'll want to consider pursuing neuropsychological testing. This is a complicated slide, but I'm going to talk you through it, that provides the work-up flowchart that you'll want to be thinking of as you assess the patient who's presenting with psychotic symptoms. Starting at the top, you're going to want to assess the past psychiatric history, prior diagnoses, and any prior history of psychotic symptoms, as we just described, and comparing them to the current presentations. For those individuals where you see that the current presentation is similar to a recognized and already known psychiatric disorder, you will want to treat the primary psychiatric disorder. But if you determine that there is no prior history of psychotic symptoms, then your next step will be that you'll want to conduct a medical and neurological work-up, and we will be pursuing the flowchart going down the right of this slide. And so our next step will be to conduct a thorough medical and neurological work-up for the patient. And what should this entail? For new onset psychotic symptoms, you're going to want to give a very careful consideration to obtaining a systematic history, including physical exam, mental status examination, and routine screening labs. You're going to be wanting to rule out organic causes for psychotic symptoms, such as trauma, specific organ failure, infections, some sort of substrate deficiencies, including vitamin deficiencies, or the presence of neurological conditions. Trauma may include a recent concussion, a fall that produced subdural hematoma, or intraparenchymal hemorrhage. Consideration for organ failure will have you observing whether the patient potentially has hepatic encephalopathy, or a brain encephalopathy due to another cause, such as thyroid disease, adrenal disease, or severe hypertension. You'll want to screen for the possibility of infections, which may be presenting with pneumonia, urinary tract infections, HIV, or meningitis. And I want to use this opportunity to tell you that since I am recording this during the COVID-19 pandemic, that we now recognize COVID-19 not only can cause pneumonia, but can also cause types of encephalopathy, including psychosis. In consideration of substrate deficiencies, you'll want to consider is the patient potentially hypoxic or hypoglycemic? Is there B12 or folate deficiency or other severe electrolyte abnormalities? And neurological conditions may include Parkinson's disease or epilepsy, new-onset stroke, Huntington's, or an unrecognized brain tumor. So the workup for a new-onset psychosis would include, on the left, elements that we would consider mostly part of a routine workup, and you may do most, perhaps not all of these. Obviously, you'll want to review the patient's vital signs, make sure that they've had a thorough and complete physical and neurological exam. Laboratory studies need to include complete blood count, serum chemistries, which will include electrolytes, calcium, phosphorus, and glucose, blood urea, nitrogen, and creatinine, as well as review of liver function tests, thyroid function studies, particularly thyroid-stimulating hormone, vitamin B12, and folate. You may want to be considering the possibility of checking ammonia levels, particularly if the patient has been prescribed valproic acid, which we know is prone to hyperammonemia. You'll see the toxicology is in red to remind you that you will definitely want to consider the possibility of other substances that might be contributing to new-onset psychosis, as well as your analysis, and where appropriate, human immunodeficiency, virus infection testing, and syphilis serologies. Depending on the history and your level of concern, you might also pursue additional workup, as indicated with the elements listed on the right of the screen. If you are concerned that the individual may have had some sort of toxic exposure, perhaps due to their employment, you might want to consider screening for heavy metals. If there is a history concerning for seizure activity, you'll want to order an electroencephalogram. If there is a concern about stroke localizing neurological signs, or new-onset or severely worsening cognitive impairment, you may want to order a brain MRI. If there is concern about pneumonia, you might want to order chest films. And if there is a more abrupt mental status changes associated with headache, fever, or meningeal signs, a lumbar puncture may be indicated. You want to consider the possibility whether the patient may have psychotic symptoms due to delirium, rather than a primary psychotic disorder. And how will you distinguish between the two? Well, delirium quite classically presents with an acute onset, which is usually not so characteristic of primary psychotic disorders, though a new-onset depressive disorder or mood disorder can occur in a somewhat acute way. But among the hallmark features of delirium, as I want to remind you, are a fluctuating course and also fragmented and unsystematized delusions. Individuals tend not to have delusions that persist or hold from day to day, and can change even hour by hour. Visual hallucinations are common. And the last element is perhaps the most important, that the key feature of delirium is impaired attention. And you will notice this in the inability of the individual to follow what you're saying or to seem to have excessive vulnerability to distractibility in the environment. Psychotic symptoms are frequently a feature of Parkinson's disease, and in fact, we see them in up to 40% of patients with Parkinson's disease. Psychotic symptoms and psychosis are highly correlated with high doses of dopaminergic agents, especially levodopa carpe dopa, but others as well, as I will mention momentarily. It is also associated with disease severity and typically occurs with more advanced disease. Individuals with Parkinson's disease and psychosis tend to be more cognitively impaired, have higher depression scores, and worse visual acuity, and there's a poor prognosis. And in fact, psychotic symptoms when present can be more disabling and cause greater caregiver distress than the motor symptoms of Parkinson's. And therefore, they pose a serious threat to the patient's ability to stay at home and maintain independence and therefore warrant very careful attention and treatment. And so going back to our flow sheet, you'll see that you're going to be conducting a medical and neurological workup as just described. And for those individuals for whom you have determined that there is indeed some sort of medical or neurological condition that seems to be causative, the next step will be to treat those underlying organic causes. However, for those individuals for whom the medical and neurological workup has been negative, your next step will be to assess medications and assess for substance use. Medications associated with psychosis are considerable. You'll see quite a number of them listed on the slide. As I want to bring your attention to those listed on the left-hand portion of the slide, you'll see, number one, many types of medications used in the treatment of Parkinson's disease, including L-Dopa and Carbidopa, but also Pramipexole, Amantadine, and Bromocriptine. These are all dopaminergic agents that are highly correlated with inducing psychotic symptoms. You will also notice, at the bottom of this column, antineoplastic agents, steroids like prednisone and dexamethasone, which you probably are familiar with. But it may surprise you to see other agents on this list, including anticholinergic and antihistaminic medications, such as diphenhydramine, hydroxazine, or even indomethacin, which is an anti-inflammatory drug. And in the column on the right, you may be surprised to see antiarrhythmic and cardiac drugs, including digitalis, quinidine, propranolol, procainamide, and even tricyclic antidepressants such as amitriptyline have been associated with case reports of producing psychotic symptoms. Stimulants also have been known to trigger psychosis, including amphetamines, ephedrine, and even thyroid, as well as sedative hypnotic medications, benzodiazepines, barbiturates, and chlorohydrate, these last ones particularly when individuals are in a state of withdrawal. What about substances associated with psychosis? Here's where I'm going to want to remind you, first of all, to consider over-the-counter medications that the patient may be taking and may not be on their medication list, including antihistamines, cold medications, cold suppressants, sleep aids, and allergy medications. You must ask about these medicines, particularly those that have, quote, PM, end quote, formulations, which usually refers to the co-presence of diphenhydramine, which you'll remember was listed as a potential causative agent of psychosis in older adults. But as well, you're going to want to take a thorough history with the patient to review potential substances of abuse, including alcohol, and rates of alcohol use and misuse are rising in the elderly. And in fact, alcohol is the most commonly misused substance in older adults. However, substance use disorders are rising in older adults in general, and rates of cocaine and opioid misuse are high and are becoming higher. So you'll want to take a good history to assess for these. Benzodiazepines can precipitate psychotic symptoms, particularly if the patient is a state of withdrawal. And concerns of withdrawal for both alcohol and benzodiazepines must come to mind in individuals who are hospitalized, who may not have given a thorough history to the physicians and clinicians at the time of admission. And while in the hospital for surgery or for some other reason, they might start to experience withdrawal and in the withdrawal state, experience psychotic symptoms. Rates of cannabis are rising in older adults as well. And in fact, cannabis is now the second most commonly abused substance among older adults. As with younger people, cannabis can precipitate psychotic symptoms. Benzodiazepines as well can precipitate psychosis. So please remember to ask all patients, regardless of age, about their potential use of these substances. Next slide. Returning to our flow sheet, again, where you have found that medications or substances may have precipitated the psychotic symptoms, your next step will be to taper or stop all offending agents and treat withdrawal as appropriate. However, if you have determined that no medications or substances seem to be etiologic or relevant to the case, your next step will be to assess the patient for cognitive impairment. And indeed, psychosis is associated with Alzheimer's disease. While it is never or almost never a presenting symptom, it is relatively common in both the middle and later stages of Alzheimer's disease. And what we see commonly are visual hallucinations, persecutory or paranoid delusions, as well as misidentification. And by misidentification, I mean that the individual has perceived a true stimulus in the environment, but has misidentified it as being something else. Psychotic symptoms associated with Alzheimer's disease are more common in women. And some experts do consider this to be a distinct phenotype associated with greater severity of cognitive impairment, worse functional progression, as well as increased mortality risk, as well as increased caregiver burden. Dementia with Lewy bodies accounts for 10 to 25% of all patients with dementia. And the hallmark core features of this dementia include recurrent complex visual hallucinations that can be extraordinarily vivid and preoccupying. Other core features that will help you recognize this dementia are fluctuating cognition with variations in attention and alertness, such as the patient might be quite lucid at one part of the day, and somnolent and less attentive later in the day. Another important aspect to highlight is that we see the onset of features of Parkinsonism occurring at the same time as cognitive impairment. This is very important to tease out in the history that you obtain from the patient and from outside a close informants, and will help you to distinguish dementia with Lewy bodies from the dementia and psychotic symptoms associated with Parkinson's disease. Because in Parkinson's disease, psychosis and dementia will occur later after the onset of the motor symptoms. A very important feature of dementia with Lewy bodies is that these individuals have extreme sensitivity to neuroleptics, particularly our typical or first-generation neuroleptic medications, but also most second-generation or atypical neuroleptic medications. And so you're going to want to avoid treatment with these agents. How else will you appreciate differences of the dementia with Lewy bodies from Alzheimer's disease? Well, there is less prominent amnestic memory loss, and again, more likely to have Parkinsonism and movement symptoms, as well to remind you the psychotic symptoms are common in the early stages, whereas psychotic symptoms are more common in middle to late stages for Alzheimer's disease. Dementia with Lewy bodies is also associated with a high prevalence of REM sleep behavior disorder, as well as autonomic dysfunction. And the autonomic dysfunction can be severe and can precipitate frequent and unexplained falls. So returning to our workup flowchart, if you have assessed the patient for cognitive impairment and have determined that this does seem to be relevant and etiologic, your next step will be to treat the neuropsychiatric symptoms associated with this dementia. However, if you have determined that cognitive impairment does not seem to be relevant and is not causative, then your next step will be to assess the patient for the presence of a primary psychiatric disorder. Primary psychiatric disorders that can cause psychosis in older adults include the schizophrenia and related disorders, including schizophrenia from disorder, schizophrenia, schizoaffective disorder, a brief psychotic disorder and delusional disorder. But as well, we see affective psychosis, including bipolar disorder and psychosis associated with major depressive disorder. And in addition, we must give consideration for the possibility of a longstanding paranoid personality disorder. Schizophrenia, as you know, typically begins in younger adults, younger than the age of 40. However, schizophrenia also may have a later onset and late onset schizophrenia is appreciated to occur between the ages of 40 to 60. As well, we now recognize that some individuals over the age of 60 may also develop for the first time a condition that appears like schizophrenia. In these instances, these individuals are diagnosed with having a very late onset schizophrenia-like psychosis. I'm going to talk about all three of these because they have different risk factors and somewhat different typical signs and symptoms. What do we know about early onset schizophrenia in individuals in later life? Well, we know that schizophrenia that begins in early life will be a lifelong disorder and one that tends to have a very heterogeneous course. Studies that have looked at the life course of individuals with early onset schizophrenia have found that about a third will have improved quality of life in their later years. However, some recent reports have noted that more typically, for perhaps another third of individuals, there will be periods of exacerbation and periods of relative remission and improvement and changeability in their conditions and their symptoms. Overall, with time, we see less severe positive symptoms than in younger individuals, more severe negative symptoms and more cognitive impairment, more impairment in domains of functioning than in younger individuals. But I do want to tell you that the memory impairment that we do see associated with schizophrenia is less severe than that seen with Alzheimer's dementia. And in fact, when these individuals are followed progressively with cognitive exams serially over time, we see more rapid declines in cognitive assessment for individuals with Alzheimer's than we do with aging individuals who have schizophrenia. We do see high rates of comorbid depression and subsyndromal depression. And here is an avenue for potential treatment, which could quite significantly improve quality of life and functioning. What are the risk factors associated with a later onset of schizophrenia? Well, interestingly, among these individuals, we see a predominance of females, whereas, as you know, for early-onset schizophrenia, the proportions of male and female are about the same. Late-onset schizophrenia is also associated with comorbid sensory deficits, particularly auditory and visual impairment, and very frequently there will be a history of social isolation or a premorbid paranoid or schizoid personality disorder. However, some of these individuals have had more relative preservation of personality and may have families and may have married, which can actually be a benefit in treatment because they may have more of a psychosocial support system in place than those aging individuals who have had an early-onset schizophrenia illness. It may surprise you to learn that actually about 23% of older individuals with schizophrenia have had a later onset over the age of 40. Again, among these individuals with late onset, we see a significant preponderance of females at a rate of seven to one, which is considerable. Patients with late-onset schizophrenia are more likely to present with apathy and some more abnormal psychomotor activity than those with very late-onset schizophrenia-like psychosis. For all, persecutory delusions, auditory delusions, inappropriate social behavior and anhedonia are common, but formal thought disorder is much less common in late-onset schizophrenia. What about other psychotic disorders? You're gonna wanna consider a possibility of a schizoaffective disorder, and the depressed type is perhaps more common in older patients, again, more common in women. But compared to schizophrenia, schizoaffective disorder is associated with better community functioning, though greater rates of acute hospitalization and poorer subjective physical and mental health functioning. In terms of brief psychotic disorder and schizophreniform disorder, you will want to make the diagnosis just as you would for a younger individual, giving the same consideration to length of time of the psychotic symptoms. And to remind you, we diagnose a brief psychotic disorder in those individuals who've had the presence of psychotic symptoms for somewhere between a day to a month, and for schizophreniform disorder, the symptoms have been present on an ongoing basis, but for less than six months. Delusional disorder is common in older adults as well. And here we see entrenched and tightly held delusions, which are fixed, false, and idiosyncratic beliefs without accompanying hallucinations. There will be no thought disorder, and the symptoms need to be present for at least a month. Again, here we also see a preponderance of females compared to males. It can be difficult to distinguish between a late onset delusional disorder that has presenting with paranoid delusions from a late onset schizophrenia, or a very late onset schizophrenia psychosis, because there is overlap in symptoms, but the good news is there is also overlap in treatment as well as prognosis. Older patients are more likely to be diagnosed with paranoid delusions and a paranoid delusional disorder than schizophrenia compared with younger patients. Bipolar disorder can also present for the first time in later life. And in those individuals with bipolar disorder, psychotic symptoms are common as they are in bipolar disorder earlier in life. For those individuals who present with a late onset bipolar disorder, we tend to see lower rates of family psychiatric illness, greater medical and neurological comorbidities, and greater cerebrovascular and ischemic changes on brain MRI. When these individuals are ill, they tend to have a greater duration of illness and spend more time in the depressed phase than in the manic phases. There tend to be more frequent episodes of illness that can be more difficult to treat. There's a high rate of suicide and mortality. And late life bipolar disorder is also associated with significantly higher risk of dementia. Major depressive disorder is common in older patients. And in fact, 25 to 50% of all admissions to inpatient geriatric psychiatry units are for older patients with major depressive disorder. Among these individuals, psychosis is present in up to 25%, which you'll notice is significantly higher than the rates of psychosis of 7% in younger adult depressed patients. Delusions are common. They tend to be nihilistic or somatically focused or poverty-based. Common ones are that the individual may believe they have an undiagnosed cancer or severe illness that will send them to various doctors to try to find out what the cause is. They may believe that they have HIV and may not believe that testing is accurate and might not be reassured by blood tests and scans. They may believe that they're running out of money, that they're going to be evicted from their home. These are poverty-based delusions. We see high rates of insomnia, a significant focus on somatic symptoms, often more than mood symptoms, and a diurnal variation where patients tend to be anxious, particularly with lower mood, greater incapacity of functioning in the mornings, early morning awakening and poor insight. Hallucinations can be seen but are less common. Psychotic symptoms may be difficult to detect, particularly for those older patients who are living alone or are single or widowed. As well, they might be difficult to detect when they take the form of somatic preoccupation for which the patient is seeing different physicians who might not appreciate the psychotic aspect of their complaints. Paranoid personality disorder is a condition that we see rates of two to 10% in outpatient mental health clinics. It is more common in males, and paranoia increases with aging and can increase particularly if there's a comorbid medical problem. This is not going to be a condition that will present for the first time in late life. And really, by definition, personality disorders have been longstanding traits of the individual over most of their adult life. It is characterized by extreme distrust and suspicion of others, excessive trust in their own knowledge and ability. These individuals tend to avoid close relationships with others, and they often search for hidden meanings in everything and read hostile intentions into the benign actions of others. They may be quick to challenge the loyalties of friends and loved ones. And this is a very difficult disorder to treat because these individuals are less likely to see the role that their own worldview is playing in their assessment of their situation and their assessment of their relationships. And rather, they may shift blame to others. They may also tend to carry long grudges regarding friends, acquaintances, and relatives. So now that we've given consideration to the workup and differential diagnosis, I'd like to review with you what would be appropriate treatments for psychotic symptoms and psychotic disorders in later life. As a general rule of thumb, whenever we treat older adults with any psychotropic medication, the first thing that we want to do is make sure that the medications that we're going to give will not cause harm. And perhaps you remember this mantra from earlier in your medical training, that we always want to start low and go slow, meaning titrating doses slowly over time, watching for any potential adverse effect, as well as potential therapeutic benefits. You are definitely going to want to avoid polypharmacy, recognizing that older patients are quite commonly being prescribed multiple other agents by other practicing clinicians, which have the potential for interactions. You're going to always want to select medication with empirical evidence of efficacy, but consideration of side effects may also drive which medication choices are best for the individual. You're going to want to frequently reassess the target symptoms and the potential side effects the patient is experiencing. And when you have been successful in alleviating psychotic symptoms and improving them, you're going to want to aim for the lowest dose that is necessary in order to improve symptom and functioning in the individual. And once the patient has had an approximately six months of stable remission of their symptoms, we strongly recommend at that point, considering tapering down gradually, slowly the dose, and to see if the patient might be able to do well off of the medication. Most individuals will not need indefinite treatment with psychotic medication, though some may. An important thing to remember is that these are difficult disorders to treat, and while you might be tempted to add medication, I'm going to urge you to hold back and be restrained about it. Instead, to consider reformulating your diagnosis, reviewing previous patient trials to see, were they adequate? Was the patient adherent with the medication? Did they take it as prescribed? And again, perhaps to review and revisit our initial flow sheet and give consideration, is there a medical, neurological, or some other pharmacologic etiology that perhaps was comorbid that you missed and might be accounting for why the patient has not been improving? With all difficult and challenging cases, it's always appropriate to consider getting help from a colleague and running the case by someone else who might have new insights or suggestions that could be helpful. Unfortunately, we have very limited studies of antipsychotics in older adults. In general, typical antipsychotics have consistently been found to be effective, but their usage is limited by the extrapyramidal side effects and tardive dyskinesia that we're all familiar with. A large trial comparing olanzapine and risperidone found that both were effective in targeting psychotic symptoms with similar extrapyramidal symptom side effect profiles. Unfortunately, at this time, we do not have any randomized controlled trials of some of the newer antipsychotic agents that you might consider, including valiperidone, acenipine, lorazidone. So when it comes to pharmacotherapy for schizophrenia and late life, I'm going to share with you some expert consensus recommendations. It is frequently recommended that first line agent might be risperidone, and while you might start at a very low dose, your final target dose may be somewhere between 1.25 to 3.5 milligrams a day. You might also consider quetiapine, again starting at a low dose of no more than 25 milligrams a day, but a final dose might be, depending on response, 100 to 300 milligrams a day. For olanzapine, you'll want to begin at 2.5 milligrams a day. The final dose, depending on response to treatment, might be 7.5 to 15 milligrams a day. And for aripiprazole, again beginning at a low dose, perhaps 2 milligrams, and the final dose may be 15 to 30 milligrams a day. Again, I want to remind you that for patients who have improvement and are stable, you'll want to give consideration to antipsychotic dose reduction over time, perhaps aiming for a final dose that is 40% of the original baseline dosage, or perhaps even lower, depending on the patient's response. I want to bring to your attention a very good paper by Kraus et al., published in 2018, which was a systematic review and meta-analysis of antipsychotic drugs for elderly patients with schizophrenia. And these authors reviewed all randomized controlled trials of antipsychotics in older patients with schizophrenia. And they reviewed a total of 18 randomized controlled trials, beginning from 1958 to 2009, looking at the primary outcome, overall symptoms, but as well secondary outcomes, including positive and negative symptoms and quality of life, social functioning, and side effects. Over 1,200 individuals were part of the study, with a mean age of 57 to 73 years of age. What the authors concluded is that while all medications showed some efficacy, olanzapine, they felt, was superior to haloperidol in overall symptoms, in negative symptoms and response, and had fewer dropouts relative to risperidone. Olanzapine was associated with less use of antiparkinsonian medications than haloperidol. Both risperidone and haloperidol were associated with higher levels of prolactin. And paliperidone had fewer dropouts due to inefficacy compared with placebo, but no significant effect for symptoms. What about treatment of psychotic symptoms in Parkinson's disease? Hallucinations, particularly visual, are more common than auditory, and illusions, particularly misperceptions of actual stimuli, are common. But in addition, we see some unusual psychotic symptoms in Parkinson's that we don't tend to see in other disorders, including passage hallucinations, which is the experience of feeling that there's some sort of object passing through one's peripheral field, and sense of presence hallucinations, in which patients will describe the feeling that there's somebody there close by that they don't actually see. As well, there can be delusions, especially persecutory delusions. The first approach is to try to discontinue medications that may be worsening psychosis, and this may involve a close collaboration with the treating neurologist to see if dopaminergic medications can be changed or lowered. But as well, you're going to want to try to institute non-pharmacologic strategies. If the patient is tending to experience psychotic symptoms at night, talk to the family about increasing the use of night lights, keeping the light on in the bathroom during the day, making sure that there's good lighting, and perhaps trying to teach the patient cognitive techniques to recognize that these are psychotic symptoms that they're experiencing rather than actual individuals in the environment. For pharmacotherapy of psychotic symptoms, you might first want to consider the possibility of adding a cholinesterase inhibitor, galantamine, rivastigmine, and denepazil. All have been reported in the literature of having some benefit in small case studies and open labels trials, although their use would be considered off-label for the treatment of psychotic symptoms in Parkinson's. In terms of antipsychotic medications, again, you're going to want to avoid all first-generation typical neuroleptics and most second-generation atypical neuroleptics. However, clozapine has been found to be efficacious. Quetiapine also may be useful. And I want to bring your attention to pimivanserin, which does have FDA approval for the treatment of psychotic symptoms in Parkinson's disease. And indeed, this is the only FDA indication for pimivanserin. But it could be a very effective agent for those individuals with Parkinson's disease who are experiencing these troubling psychotic symptoms. Antipsychotic medications have FDA approval for use in schizophrenia, bipolar disorder, major depression, and for the psychosis associated with Parkinson's disease. However, there is not an FDA indication for dementia, anxiety, or insomnia. And the risks of antipsychotic medication in older adults is considerable. They can cause sedation, anticholinergic symptoms, orthostatic hypotension, extrapyramidal symptoms, QTC prolongation, as well as metabolic side effects or kidney damage. However, I want to particularly bring your attention to the last three, cerebrovascular adverse effects, death, and cognitive decline. Next slide. Because there is a specifically increased risk for these three adverse effects, particularly in dementia patients. This table provides a nice summary for you comparing clozapine, risperidone, olanzapine, quetiapine, suprazitone, and aripiprazole in the treatment of psychotic symptoms in older adults. And you can see how they compare in terms of a number of features. I want to point out to you a couple of things. First of all, that clozapine is highly associated with causing somnolence, weight gain, dyslipidemia, diabetes, and orthostatic blood pressure changes. Risperidone is highly associated with causing extrapyramidal symptoms, particularly rated to dosage and the higher dosage of risperidone. There's also an increased risk for tardive There's also an increased risk for tardive dyskinesia and hyperprolactinemia. Olanzapine is more associated with increased weight gain, dyslipidemia, and diabetes. And quetiapine also can cause somnolence, weight gain, dyslipidemia, and diabetes, and orthostatic blood pressure changes, though at rates that are somewhat lower than olanzapine and clozapine. As with younger patients, anytime you are prescribing an antipsychotic medication for an older patient, you're going to want to obtain informed consent. But also remember that these are the critical components that you need to review with the patient, their diagnosis and prognosis, and why this is recommended treatment, the risks and benefits of the treatment, alternative treatments, if appropriate, and the risks and benefits of those, as well as the risks of refusing the treatment, which can be considerable. And it is important that informed consent be ongoing throughout the course of time that you are prescribing for the patient and continue to review these with the patient. I want to remind you that psychosocial treatment is very important for our older patients who have a schizophrenia illness in late life, as it is for younger individuals. We know that psychosocial treatment is an important, stabilizing, adjunctive part of what we can offer these individuals and can have a huge impact on quality of life and functioning. These can include assertive community treatment, family-based services and skills training, as well as attention to psychosocial interventions where there is comorbid alcohol and substance use disorders, as well as psychosocial interventions for weight management, where that is a concern, whether it was pre-existing or prior to initiation of treatment with an antipsychotic medication or whether it developed with treatment with an antipsychotic medication. I wish that there were more psychosocial rehabilitation programs specifically geared for older adults with schizophrenia, but where they exist, they have been found to be quite helpful, particularly those that focus on skills training that improve function and skills training that improve psychosocial skills. One example is called the HOPES program, which has integrated skills training and healthcare management, and where appropriate, some sort of supportive employment might be helpful for some of these individuals as well. What about the use of ECT? Well, ECT, or electroconvulsive therapy, is a safe and effective treatment at all ages. We do know that there are transient cardiovascular adverse effects, particularly elevations in blood pressure, and potential for changes in rhythm that require close monitoring during the treatment setting, and that cognitive disturbances occur more frequently in the elderly. However, ECT is an extremely effective treatment for major depression in late life, and perhaps should be considered a first-line treatment for those individuals who have a late-life depression with psychotic symptoms as well. There is a small literature that does also support the use of ECT for those individuals with schizophrenia and late life who are medication-resistant or for whom medication side effects are intolerable. So, in summary, as we have reviewed during this hour, psychotic symptoms are common in late life, and they are seen in a variety of disorders. A thorough evaluation is absolutely necessary to establish the diagnosis and to determine possible underlying causes. And I want to remind you to always consider both pharmacologic and non-pharmacologic strategies, and these must be implemented and must be tailored to the specific disorder and to the specific individual. And now I would like to go through with you four questions that pertain to this talk as a way of review. So, let's begin with question number one. Compared to patients with a primary psychotic disorder, patients with delirium are more likely to have A. visual hallucinations, B. delusions, C. impaired attention, or D. agitation. As you can see, the correct answer is C. impaired attention. Question two. Which of the following are core features of dementia with Lewy bodies? A. extreme sensitivity to neuroleptics, B. onset of Parkinsonism at the same time as dementia, C. complex visual hallucinations, or D. all of the above. Next slide. If you selected D. all of the above, you have the correct answer. Three. Risk factors for late onset schizophrenia include all of the following except A. female gender, B. premorbid histrionic personality disorder, C. sensory deficits, or D. history of social isolation. The correct answer, as you see, is B. premorbid histrionic personality disorder. And finally, our last question. Efficacious medications for the treatment of psychotic symptoms in Parkinson's disease include all of the following except A. clozapine, B. quetiapine, C. flufenazine, or D. or D. pimivanserin. Next slide. If you selected C. flufenazine, then you have selected the correct answer. So I want to thank you for your attention and I hope that you have enjoyed the presentation and feel that you are more knowledgeable now about psychotic disorders in later life. Since you have access to these slides, I do want to point out to you three additional resource slides at the end of this slide deck. And here are some additional slides that may be of interest to you. This table compares key features and characteristics of delirium, dementia of the Alzheimer's type, and depression, which will help you better distinguish and differential diagnosis among these three common conditions that can cause psychotic symptoms. This table compares early-onset schizophrenia, late-onset schizophrenia, and very late-onset schizophrenia-like psychosis in terms of their core features and, again, will help you have a better grasp and understanding of how phenomenology differs among these three conditions. And this final table compares the key features between psychosis of Alzheimer's disease and that associated with schizophrenia in terms of types of hallucinations, prevalence rates, past history, and need for maintenance antipsychotic therapy. I hope all of these tables will be of use to you and that you will feel more confident in your treatment now of psychotic disorders in older adults. Thank you very much.

psychotic disorders

late life

prevalence

psychotic symptoms

older adults

antipsychotics

pharmacotherapy

psychosocial treatments

evaluation