Welcome back. This is the next session in this course. We're going to talk about bipolar disorder among older adults. I have no conflicts of interest to disclose for this presentation. We're going to talk about epidemiology of bipolar disorder among older adults. We'll go through the assessment of bipolar disorders and then talk about the evidence-based treatment for bipolar disorders among older adults. As you know, the DSM-5 indicates that bipolar disorder is defined as a condition that is characterized by recurrent and or cyclical episodes of mania or hypomania and depression. There are two subtypes of bipolar disorder, bipolar disorder 1 and bipolar disorder 2. As you all know, bipolar disorder 1 is diagnosed when an individual meets the criteria for a manic episode. The manic episodes may have been preceded by or may be followed by a hypomanic or major depressive episode. If you have had a manic episode, that means you meet the criteria for bipolar 1 disorder. For bipolar 2 disorder, the individual meets the criteria for a current or past hypomanic episode and criteria for a current or past major depressive episode. For bipolar 2 disorder, the individual must not meet the criteria for a manic episode, and if they do, then it's a bipolar 1, not a bipolar 2 disorder. If you look at bipolar 1 disorder in the United States, the prevalence is about 1.5%. That is a 12-month prevalence. For men, it is 1.6% and for women, it is 1.5%. So the 12-month prevalence is about the same for both men and women. The mean age of onset in the United States is 22 years, and it's slightly older for men. That is 23 years compared to 21.5 years for women. 90% or more individuals have recurrent mood episodes after the initial manic episode. 60% of the manic episodes occur immediately before a major depressive episode. That's why it used to be called manic depression. So mania first followed by depressive episodes. For bipolar 2 disorder, the 12-month prevalence is lower at about 0.8%. 50% of individuals have a new mood episode within a year after the first episode. When you look at these two disorders put together, the lifetime risk of suicide is 20 to 30 times higher than the general population. Approximately 5 to 6% of individuals with bipolar disorder die by suicide. That is a very high risk percentage. When you look at bipolar disorders, they are highly heritable, and the evidence from bipolar 1 disorder is that the prevalence of bipolar disorder in first-degree relatives is 5% to 10%, so about 5 to 10 times higher than the general population. So it's a highly heritable illness, and the risk of suicide is very high in individuals with bipolar disorder. When you look at comorbidities, for bipolar 1 disorder, the most comorbid condition is anxiety disorders, followed by alcohol use disorders, followed by intermittent explosive disorders. Whereas for bipolar 2 disorder, anxiety disorders is the most comorbid condition. Substance use disorders, which also includes alcohol use disorder, is the next most comorbid condition at 37%, followed by binge eating disorder. At 14%. Now, what are the differential diagnoses for bipolar disorders? For bipolar 1 disorder, bipolar 2 disorder is a differential diagnosis because you have to make sure that the individual is not having any, is having either the mood swings, which includes hypomania, mania, and or depression. If the patient meets a manic episode, has a history of manic episodes, then it's a bipolar 1, not bipolar 2. You have to rule out bipolar disorder due to other medical conditions. Whereas in bipolar 2, cyclothymic disorder becomes a consideration. The cyclothymic disorder is individuals have mood fluctuations, and they have it chronically. That means for a period of more than two years, and these individuals meet the criteria for a cyclothymic disorder. Substance-induced or medication-induced bipolar disorder is a differential diagnosis for both conditions. Major depressive disorder, generalized anxiety disorder, schizoaffective disorder are also differential diagnosis for both conditions. Panic disorder, post-traumatic stress disorder, ADHD, and personality disorders are also a differential diagnosis for both bipolar 1 and bipolar 2. When you look at older age bipolar disorder, or OABD, the International Society for Bipolar Disorders Task Force recommends defining older age bipolar disorder as bipolar disorder occurring for the first time in individuals at or above the age of 50 years in age. What we know is 25% of all cases of bipolar disorder occurs in individuals greater than 60 years in age, and 10% occur in individuals greater or equal to 70 years in age. So it's not uncommon in later life. Now, if you look at the point prevalence of bipolar disorders in older age, that is OABD, the prevalence is between 0.1 and 0.5%, so about one-fifth of the younger adult population. If you look at lifetime prevalence, it's between 0.5 and 1%, again, less than what you would see in younger adults. What we know is 10% to 25% of all older adults who are diagnosed with a mood disorder have met the criteria for bipolar disorder. When you look at where these individuals are more commonly seen, they're seen in emergency room settings where individuals present, 17% of the older individuals presenting with a mood episode meet the criteria for a bipolar disorder. When you're looking at residential psychiatric care programs, the prevalence is about 17.4%. When you look at individuals who are chronically institutionalized, like in the nursing homes or long-term care hospitals, the prevalence is about 9.7%, and among older nursing home residents, it is about 3%. 70% of cases of older age bipolar disorder cases are seen in women. Just like what I said in the psychotic disorder stock, more bipolar disorder is seen in women. Depression, rather than hypomania or mania, is the presenting symptom in older age bipolar disorder. These individuals may have hypomanic or manic episodes after a depressive episode. These individuals present with more recurrent and more severe depressive episodes, and there is longer latency period between the first and subsequent mood episodes. That's more common. More depressive episodes, more severe depressive episodes, and longer episodes of depression. They have a less family history of mood disorder than in the typical onset bipolar disorder. However, these individuals have more stressful life events when compared to age match controls. What we also know is OABD individuals have greater cerebrovascular disease and other neurological disorders. Again, very similar to the psychotic disorders. Older individuals who present with mood symptoms and bipolar symptoms, you always have to rule out a secondary medical condition because that may be the reason why the patient is presenting with the mood swings. If you have manic symptoms, vascular changes are usually seen in the right cerebral hemisphere. If the patient has depressive symptoms, usually the vascular lesions are in the left cerebral hemisphere. Individuals with older age bipolar disorder have greater medical comorbidities, especially cardiovascular and metabolic disorders. Comorbidities are also associated with worse clinical outcomes and greater rates for suicide. If you have an older adult with bipolar disorder, who has more medical conditions, you have to be very careful of monitoring them for suicidal ideation and completed suicide. A very good aftercare plan once discharged from the hospital is needed. When you look at psychiatric comorbidities, they are more common when compared to age match controls, but they're not as common as what you would see in an early onset or typical onset bipolar disorder. When you look at comorbid psychiatric disorders, the 12-month and the lifetime prevalence, alcohol use disorder seems to be the most common at 38.1%, followed by dysthymia, 7.1% is a 12-month prevalence and 15.5% is the lifetime prevalence. Generalized anxiety disorder, the 12-month prevalence is 9.5% and lifetime prevalence is 20.5%, followed by panic disorder, 11.9% and 19% respectively. Again, substance use, mood disorders and anxiety disorders are the most comorbid conditions in older age bipolar disorder. Very similar to what you would see in the early onset bipolar disorder or typical onset bipolar disorder. Now, are there any differentiating features between older age bipolar disorder and early onset bipolar disorder? And the answer is yes. Age of onset is different. So, older age bipolar disorder, individuals are over 50 years in age, whereas early onset or typical onset, it is less than 50 years of age. Family history is less likely in older age bipolar disorder compared to early onset bipolar disorder. Presenting symptom is usually depression in older age bipolar disorder. Remember, I said these individuals have more severe depressive symptoms, longer depressive episodes, and whereas in early onset bipolar disorder, mania or hypomania is usually the presenting symptom. Manic symptoms, much less likely in older age bipolar disorder, more likely in early onset bipolar disorder. Latency between first and second episodes, significantly longer in older age bipolar disorder, whereas shorter in early onset bipolar disorder. Cerebrovascular disease are much more likely in older age bipolar disorder, less likely in early onset bipolar disorder. Medical comorbidities, more likely in older age bipolar disorder, less likely in early onset bipolar disorder. Psychiatric comorbidities, less likely in older age bipolar disorder, more likely in older age bipolar disorder. Cognitive dysfunction, more likely in older age bipolar disorder, less likely in early onset bipolar disorder. Healthcare service utilization, significantly higher in older age bipolar disorder compared to early onset bipolar disorder. Very similar to psychotic disorders in late life where these individuals have more medical problems, less family history, more cerebrovascular disease, more cognitive dysfunction, and greater service utilization. So you're seeing a theme through all of the psychiatric disorders in late life that you do have to rule out medical disorders and cerebrovascular disorders and cognitive disorders before you fix the diagnosis of a particular psychiatric disorder in late life. Workup, very similar to what I said in the psychotic disorders lecture. A good history, including history from collateral sources, a thorough mental status examination, including cognitive assessments. So whether you're doing the Montreal Cognitive Assessment, the MOCA, this St. Louis Mental Status Examination, SLAMS, whichever it is, you should do that regularly in these individuals because these individuals may have significant cognitive decline. You should do a physical examination to rule out comorbid medical disorders. Like if you remember I said the Parkinson's disease example, so you should rule those kind of things out, or a cerebrovascular disease that may actually cause hemiparesis or hemiplegia. And you should complete standardized assessment skills, and we'll talk about one or two of those. Neuropsychological testing is usually indicated if you're not able to clarify whether this individual really has bipolar disorder versus a major depressive disorder or a primary neurocognitive disorder. That is very helpful. You should do, like I said, the focus physical examination to rule out a neurological or a neurovascular disorder. Order appropriate investigations that includes lab work to rule out medical conditions like hyperthyroidism, urinary tract infection, pneumonia, and you should always do a urine drug screen because like I had said earlier, older adults are continuing to use substances like they did before in their younger age. The only issue is that they are not able to tolerate the effects of the drugs of abuse and can have more sort of cognitive issues, more mood swings, more psychotic symptoms. Once you diagnose these medical conditions, you treat these first, remove the offending agents, and then you start embarking upon treatment for bipolar disorder and older adults. So just like psychotic disorders, good history, complete mental status examination, including cognitive assessment, appropriate laboratory investigations, including MRI scans to rule out cerebrovascular disease and neuropsychological testing. If you are in doubt of what is the etiology for the mood swings in these individuals, remove the offending agent, remove the drugs of abuse, treat the underlying medical condition, and then treat the mood symptoms that are persisting after you do all of the above. Among the common screening tools, we use the mood disorder questionnaire to rule out a bipolar disorder possibility. We may use young mania rating scale in certain situations where the patient is presenting with significant symptoms, so we want to rate the severity of the illness. Other scales that have been useful, though not specific for older adults, is bipolar spectrum diagnostic scale, the hypomania personality scale, and bipolar depression rating scales. I have not used the last three, but I do use the MDQ on all new assessments and any patient presenting with mood instability, and in certain cases where we really need to rate the severity of the manic episode, I have used the young mania rating scale. Now treatments, both non-pharmacological and pharmacological treatments have been found to be effective in the treatment of older age bipolar disorder. Among the non-pharmacological management techniques, the traditional CBT interpersonal therapy, you know, problem solving therapy, have not been studied in older age bipolar disorder. The two studies that I could find that have shown benefit in older age bipolar disorder, they are the medication adherence skills training, the MAST bipolar disorder, and the manual-based care model, the BCM, have been found to be effective. In the MAST BD, medication adherence, medication management ability, depressive symptoms, and overall quality of life have been shown to be improved. Among the manual-based medical care model, the had high satisfaction of patients, high follow-through rate, and good tolerability where patients did not drop out. They are not primary treatments, they're adjunctive treatments to medications that I'm going to talk about now. Among the pharmacological agents, lithium, as you all know, is the prototypical drug, has been studied in older age bipolar disorder. Anticonvulsants have been studied, antipsychotics, antidepressants, benzodiazepines, and electroconvulsive therapy have been studied. Ketamine has been studied in some cases, but there is no great data, so that's why I did not include that in this presentation. Lithium is the drug that has had the most amount of trials. It is most beneficial for manic symptoms. It is most beneficial for maintenance treatment. It is not as good for depressive symptoms, and it is also not very good for individuals who have more neurological comorbidities. The strong evidence that lithium decreases the risk for suicide, even in older adults, and may reduce the risk for cognitive decline in older adults. That is what the data has shown. Lithium remains the drug of choice for maintenance monotherapy in older adults. The dosing of lithium is 25 to 50 percent of the daily adult dosages, and the lithium levels we try to maintain between 0.4 and 0.7 milligrams per liter. Prior to starting lithium in older adults, you of course have to do a medical workup, mainly making sure that the renal functioning, thyroid functioning, and cardiac functioning are good. Side effects, as you all probably know, weight gain, sedation, and weight gain remain the top two side effects for lithium use, followed by gait impairment, hypothyroidism, especially older women, edema because of water retention, renal dysfunction, and cognitive impairment. Cognitive dulling, not dementia. When we are prescribing lithium, as with the younger adults, you have to make sure that you are not co-prescribing the lithium with thiazide or loop diuretics because they preferentially absorb lithium for sodium, so lithium toxicity can occur in normal doses. You're not using the angiotensin converting enzyme inhibitors, the ACE inhibitors, or NSAIDs because they all can cause lithium toxicity even at normally prescribed doses of lithium. What about anticonvulsants? There is only one randomized controlled trial that looked head-to-head lithium versus divalproic sodium. This trial was in individuals with bipolar 1 disorder who were above the age of 60. They had manic, hypomanic, or mixed episodes, so they did not look at depressive episodes. Lithium target concentration was 0.8 to 0.99, and divalproic sodium target concentration was 80 to 99 micrograms per ml, and the trial lasted nine weeks. Among individuals who had inadequate response to either randomized drug, at three weeks, open adjunctive respiradone was provided. Why respiradone? As you heard in the first talk that I gave, respiradone is usually the first antipsychotic medication that the geriatric psychiatrists reach out to. The other antipsychotics are olanzapine, quetiapine, and adiproposol. Respiradone still has that standard that we are using. Respiradone was also used as an adjunctive treatment for mood stabilization. In this trial, if patients did not have adequate response, the response at nine weeks, that is at the end of study, between lithium and divalproic sodium was very similar. We are comparing apples to apples or oranges to oranges. They're basically similar in helping with the mood swings. Attrition rate was also similar between both drugs. Lower at three weeks, as expected, and higher at nine weeks. The two groups did not differ from each other in sedation, but individuals receiving lithium experienced more tremor. Divalproic sodium is as good as lithium, or lithium is as good as divalproic sodium among older adults with bipolar disorder who present with manic, hypomanic, or mixed episodes, and are equally well tolerated. That's what this only randomized control trial we have to date in older age bipolar disorder showed. What about people ask about lamotrigine? What is the evidence for using lamotrigine in older age bipolar disorder? There is a retrospective review done by Martha Sujatovic and colleagues that included individuals over the age of 55 with bipolar 1 disorder. They compared lamotrigine, lithium, and placebo, and what the investigators found was that lamotrigine delayed the intervention for any mood episode and for a depressive episode when compared to placebo, whereas lithium delayed any time for intervention for any manic, hypomanic, or mixed episodes when compared to placebo, so not as good for the treatment of acute depressive episodes in bipolar disorder. Lamotrigine was very well tolerated with back pain and headaches being the most common adverse effects, but there were no rashes, so rash was not an issue in this retrospective trial. In lithium, the common adverse effects noted by the investigators was dyspraxia, tremor, xerostomia, that is dry mouth, headache, infection, amnesia, dizziness, diarrhea, nausea, and fatigue, so sedation was a problem, some cognitive dulling as with the previous randomized control trial. Also, an important thing to talk about lamotrigine, it does have the best cognitive profile when compared to other anticonvulsant mood stabilizers. I'm sure that all of you have noticed this in your younger patients. Lamotrigine appears to be the best among the lot. Topiramide appears to be the worst of the lot for causing cognitive dulling with lithium and the other sort of anticonvulsant mood stabilizers coming somewhere in between, but remember, lithium does not cause dementia. It actually is protective against dementia. It causes cognitive dulling, not cognitive decline. When you look at antipsychotic medications, in the U.S., the following antipsychotic medications are approved for the treatment of bipolar disorder. These include aripiprazole, acepinazepine, caraprazine, olanzapine, quetiapine, and quetiapine accidental release, respiradone, and zeprazidone. For acute bipolar depression, caraprazine, olanzapine, fluoxetine combination, OFC, or Symbiax is the trade name. Lametoperon, lorazadone, and quetiapine are approved. Caraprazine, the OFC, and quetiapine are approved for monotherapy, whereas lametoperon and lorazadone are approved for both monotherapy and as adjuncts to lithium or divalproxodium. Now let's look at each of the antipsychotics and see what the trials show. So when you look at quetiapine, there is a post-hoc analysis of two monotherapy trials. The doses of quetiapine were between 400 and 800 milligrams a day, so that is a pretty hefty dose for older adults, but that was the trial that was done. These individuals were 55 years and older and had bipolar disorder with mania. What the investigators found was that the patients started to have response at day four of treatment, and at day 21, which was the end of the trial, the patients had significant improvement in symptoms from baseline. So again, quetiapine is effective at fairly large doses among older age bipolar disorder patients. Common side effects, as can be expected, with the quetiapine in the quetiapine trial, dry mouth, somnolence, postural hypotension. Surprisingly, insomnia was a side effect, although many people use quetiapine as a hypnotic agent. Weight gain and dizziness were the side effects. So when I use quetiapine to treat bipolar depression, I usually tend to start low, go slow, and try to go slowly to the doses that they've recommended. I have never gone to 800 milligrams. 600 milligrams is what I have used maximum dose for an older age bipolar disorder patient with good benefit, you know, and monitoring of adverse effects. When you look at asinopine, there is no randomized control trial. There is a 12-week open-label trial, which used adjunctive asinopine among individuals who are above the age of 60 who had inadequate response to previous bipolar disorder drugs. What the investigators found in this 12-week trial was that there was an improvement from baseline on the BPRS and on the clinical global impression of change. So there was overall improvement in symptoms. There was improvement in manic symptoms and depressive symptoms. So asinopine may be a drug that could be used in individuals with both manic and depressive symptoms. The mean dose was 12 point, sorry, 11.2 milligrams per day, which is about half the maximum dose for younger adults. Most common adverse effects were GI side effects, restlessness, tremors, cognitive difficulties, and sluggishness. And I'm certain that the side effects were more at the higher doses of medication. I have used it on a couple of patients with fairly good tolerability at under 10 milligrams. So I've never gone beyond that because patients are not able to tolerate higher doses of asinopine. Lorazodone. There is a post-hoc analysis, again done by Dr. Sujatovic, of two RCTs of lorazodone. One is a monotherapy study, other is a combination or an adjunct treatment study. And these both studies were individuals who were 55 years and older who met the criteria for DSM-IV-TR criteria for bipolar I depression. The monotherapy study doses were 20 to 60 milligrams a day or 80 to 120 milligrams a day when compared to placebo. So there were two dosing ranges, 20 to 60 or 80 to 120. The adjunctive therapy use flexible doses of lorazodone between 20 milligrams and 120 milligrams. And these were individuals who had not responded adequately to lithium or divalproxodium. And the change was, the outcome they were looking for was the change at week six for the Montgomery-Asberg depression rating scale or the MADRS. What the investigators found was that the monotherapy study was effective. That means lorazodone at six weeks improved MADRS when compared to individuals who were, you know, receiving placebo with a large effect size of 0.83. So I use lorazodone before any of the other drugs for treating acute bipolar depression, even an older age bipolar disorder because of this particular data. However, the adjunctive study did not show any significant benefit and the P-value was 0.3. So there was no statistically significant benefit of adding lorazodone to either lithium or divalproxodium. When you look at discontinuation rates, lorazodone actually was well tolerated. When you look at the monotherapy trial, it was very similar to placebo. When you looked at the adjunctive trial, that actually was less than placebo. And lorazodone, as you all know, has minimal effects on metabolic values. So it doesn't cause significant hyperlipidemia, hyperglycemia or significant weight gain. So like I said before, I use this if I want to treat this medication, if I want to treat acute bipolar depression among older age bipolar disorder patients based on this data. When you look at antidepressants, we only have one population-based retrospective study. It was mainly in individuals over 66 years of age and they were compared to a control group. What the investigators found that antidepressants did improve likelihood of admission for manic or mixed episodes. So the patients who were receiving antidepressants had half the number of admissions compared to individuals who were not receiving this medication, but there was no effect of antidepressants on depressive episodes. The way I use antidepressants in individuals with older age bipolar disorder is I use it to treat comorbid conditions. As you saw before, anxiety disorders, especially generalized anxiety disorder and panic disorder are highly comorbid in these individuals. So I use it to treat comorbid condition when the patient is also receiving and mood stabilizer coverage. So usually for depressive episodes, it's residue and if it's manic or hypomanic episodes, you know, it's either lithium or divalproic sodium or any one of the antipsychotic medications like quetiapine or asinopine. And I use the antidepressant to treat comorbid conditions and it is not effective. As in younger adults, it is not effective to treat bipolar depression. What about benzodiazepines? We commonly encounter in our clinic that a lot of these individuals are treated with benzodiazepines to treat comorbid anxiety because as I said earlier, generalized anxiety and bipolar disorder and generalized anxiety and panic disorder are very common. There are two studies that have looked at clonazepam in individuals with bipolar disorder versus major depressive disorder and both studies have shown the same thing. Individuals who are receiving clonazepam who have bipolar disorder don't have significant benefit from the clonazepam whereas individuals receiving major depression have a better response. So I try not to use, you know, benzodiazepines to treat acute anxiety or anxiety. In these kind of situations, I have tend, again, this is an off-label use, I have used other anticonvulsant mood stabilizers like divalproxodium or gabapentine to treat comorbid anxiety. I've also used pregabalin because there is some evidence that it may be beneficial to treat comorbid anxiety. I do not use benzodiazepines because of this data and the fact that there is clear evidence that benzodiazepines increase the risk of cognitive decline, increase the risk of falls and, you know, they may be the gateway drug to older adults using other drugs, including cannabis. So I preferentially try not to use benzodiazepines to treat patients with bipolar disorder because, as you saw in the earlier slide, substance use disorder is the second most common comorbid condition among these individuals. What about electroconvulsive therapy? There is evidence that electroconvulsive therapy is very helpful in individuals, especially who need quick and robust clinical response. This is the go-to treatment when patients are in a situation where they have significant depressive symptoms or refractory manic symptoms. You know, they are very helpful, as you know, for people who are suicidal or homicidal. Those are at imminent risk. They're very helpful for catatonic patients. They've also been shown to be helpful for individuals who have refractory psychotic symptoms in mania or depression. They're also very helpful for agitated patients and they're very effective for medically unstable patients. All you need to get is you need to inform the anesthesiologist and get a medical clearance so that they can have the ECT treatment. Effectiveness is about 80%, so it is very effective. Usually unilateral treatment, right? Unilateral treatment. If patients don't respond to it, you go to bilateral treatment. Individuals with bilateral treatment may have greater time for postictal recovery and memory impairments, but there is no evidence, as I said earlier, that ECT increases the risk of dementia. There are two very well-done, large meta-analyses looking at this issue and they did not find any evidence that ECT increases the risk of dementia. This is a table that we developed and we use this and it is published actually in my paper on older age bipolar disorder that was published in Drugs in Context. So this is the algorithm, if you can call it, that I use for manic episodes. You know, lithium is my first go-to treatment. It is also the go-to treatment for maintenance monotherapy for older age bipolar disorder. The dose is about a quarter to half of what is the adult dose. You're looking at 0.4 to 0.7 milliequivalents per liter. As with all medications, older adults tolerate this medication less. Sedation becomes more of an issue. At higher doses, people can have more cognitive dulling, can cause weight gain because of water retention, but it is a very effective medication to decrease their sedality. And there is also evidence that it is protective for cognitive decline. Anticonvulsant mood stabilizers are good for people who have mixed episodes. So those patients who do not have a good response to lithium I use for mixed manic episodes, I use divulproxodium or the anticonvulsant mood stabilizers for individuals who are rapid cyclers. And those individuals with comorbid medical or psychiatric disorders. Dosages are about 25 to 50% of adult doses. They're, as with all other medications, less well-tolerated by older adults. Atypical antipsychotics, you know, can be used. I use them as third line for treating manic symptoms in older age bipolar disorder, but you may use it first line. There is nothing wrong with doing that. This is just what we use, you know, to keep our treatment standardized. Useful for both manic episodes and maintenance treatment as with the previous drugs, a quarter to half the adult dose, less well-tolerated than in younger adults, more metabolic symptoms. And if you're using in individuals who have cognitive impairment, you have to be very careful because the risk of cerebrovascular adverse effects and death is higher. For depressive episodes, lithium is not all that effective. We use lithium for maintenance treatment as before half to quarter the adult dose, 0.4 to 0.7 milligrams per liter, less well-tolerated. Anticonvulsant mood stabilizers, lamotrigine is better for bipolar disorder, bipolar depression, I should say, than lithium. Atypical antipsychotics, if the patient has an acute depressive episodes, like I had said before, I use lorazodone monotherapy. As with the evidence available, I have not found it to be very effective in augmenting either lithium or divalproxetamine. I usually taper and discontinue the medications. You can use olanzapine fluoxetine combination. We have, in case-by-case basis, we have used that. The reason for not using it more commonly is that the olanzapine causes significant metabolic side effects. And many of our patients have comorbid diabetes, comorbid hyperlipidemia, so we're a little more careful. You have to do a metabolic workup when you use atypical antipsychotic medications. And if you're using atypicals or typicals, and in this case, atypicals, you have to watch if the patient is cognitively inclined because the risk for cerebrovascular adverse effects and death are higher in these individuals. ECT, mainly for refractory symptoms, psychotic symptoms, catatonic symptoms, severe agitation, people who are actively suicidal or homicidal, right unilateral. If that doesn't work, how many right unilateral? About five or six. If that doesn't work, then you switch to bilateral. Bilateral has greater cognitive postictal confusion and recovery time, but no risk for dementia. Psychosocial treatments are adjunctive and not really primary treatments. Benzodiazepines have not shown to be very effective in these individuals. Antidepressants, like I said before, are good for comorbid conditions, but not really for treating depressive episodes. And here are the references, and I will now answer the questions. So the first question is about a patient with longstanding bipolar I disorder in her 70s on a lansipine 17.5 milligrams a night Depakote, still frequent hypomanic episodes, also on amantadine, no clear history of substance use, unclear on high doses of medications. Any things to consider? Definitely ECT, because if you have tried these medications and it's not really helped, I think ECT definitely comes top of the line for this particular patient. So I would do that. The other thing, if the patient has still not responded, maybe you could taper off the patient from the Depakote and try lithium. I'm not sure if the patient has had lithium or not. So that's another consideration. So ECT is my first go-to in this particular patient. The next question is, can you comment on the risk of lithium toxicity in patients taking calcium channel blockers, like amilodipine? I've had patients on amilodipine with no issues. It's mainly the thiazide and the loop diuretics and the ACE inhibitors and NSAIDs. Amilodipine, I've not had problems and I've not seen that in the literature. So I think you can safely prescribe lithium in that patient. The next question is what agents do you use for short-term sleep problems? So if it's insomnia you're talking about, we usually use melatonin as our first choice because it's a nutraceutical, doesn't have significant adverse effects. We use trazodone and people worry about manic switches with trazodone. But if you have looked at our data, it shows that SSRI antidepressants don't cause significant manic switches. That was the old school of thought. They don't really cause, it's the tricyclic drugs that cause the manic switches. So I use trazodone as second line if melatonin doesn't work. Third line, we use metazapine at small doses not to treat the depressive symptoms but to help with the sleep. Have I used doxepine in these individuals? Yes, if the patient has had good sort of mood stabilizer coverage, doxepine becomes a drug that we can use between three and six milligrams. Though keeping in mind that tricyclics increase the risk of manic switches, but I've not had any patients have mood instability with doxepine. Do I use other drugs like quetiapine to help with sleep? I have from time to time on a case by case basis, but not as a norm. Could you use any of the Z drugs? Absolutely, if you're using it for short term with the very clear indication that the prescription is not gonna be renewed, you're going to just try to work with this. And of course, we have not done talk on sleep disorders as part of this course, but we may do it in the future. We do one every year at the AAGP and we talk about CBTI, that is CBT insomnia, highly effective for treating insomnia. Next question is what about oxcarbazepine? Yes, absolutely, you don't need a level, but the data for using oxcarbazepine is not there for bipolar disorder in older adults, but definitely as I've said before, if the patient is not responding, it is fine to try that medication as an adjunct. In my personal opinion, I have not found it to be very helpful as monotherapy. Even yesterday, we had a patient who had not responded. So we spoke about that and said that we'll try it. If it works great, if it doesn't, we will do a quick trial and taper it off. So the next question is did acinopine benefit bipolar depression? From my review of the data, it really helped with the manic and the hypermanic episodes and not with the depressive episode. So I use lorazodone instead of acinopine, but again, it's worth a try. And remember, it was an open-label trial, not a randomized control trial. The next question is, is there any evidence that antipsychotics increase the risk of cerebrovascular disease or death among older individuals with dementia? There is actually good evidence. And when I do the BPST talk at the end of the day, I will show you that evidence. It is not the dementia. It is the age and the changes, brain changes, and the cardiovascular and metabolic changes that are associated with the age are the risk factor for both cerebrovascular events and death. So I always tell all my older patients and their family members before I use an antipsychotic medication, hey, I'm gonna use this medication. We have tried everything else. Here, we're using it. We have to monitor for risk factors. That includes metabolic risk factors, cardiovascular risk factors. And we want to make sure that the patient is active because evidence is that patients who are more sedentary are at higher risk of developing this side effect. So try not to use it at doses where it can actually sedate the patient. Cardiac workup. Next question is what cardiac workup for lithium? Mainly EEG. And if EEG is abnormal, then I refer to a cardiologist for additional workup, including an echocardiogram. So that's the workup we do. What about antidepressant sparking mania? Thank you for asking that question. Like I said, if you look at the data, that was the older data, is that antidepressants do the manic switches, but the newer data is that antidepressants, especially the SSRIs and SNRIs, don't really do all that much of manic switches. It is a tricyclic antidepressants that are the main culprit. So I have used antidepressants for treating comorbid conditions in bipolar disorder in old age with good mood stabilizer coverage. The next question is, do you tend to avoid using lamotrigine if PO route is unreliable? You know, thank you for asking that question. So I've not had any patients who have not been able to take it PO. That might be a problem. You might need to use other medications which come in the liquid form to treat these symptoms or IV form. Like, you know, you wanna give IV Depakote or IM Depakote, you know, sorry, IV Depakote, not IM, IV Depakote, that might be. So unfortunately, I'm not able to say that because I've not had any patients who have not been able to take it PO. Is the high incidence of female correlates with more willingness to treatment? Excellent question. Possibly, that is one of the reasons, but there may be other biological reasons that may be predominating why more psychotic disorders are seen in older adults and why more, by older age, bipolar disorder, 70% of the patients are female. So we are not yet sure, but I think that may be one of the reasons maybe that older women may be seeking treatment mean more than older men. So I hope I have answered all your questions. You know, in the end of the day, we will have a few minutes and I'm happy to take questions on any of the three topics that I'm talking about at that time. Thank you very much.

bipolar disorder

older adults

epidemiology

treatment approaches

comorbidities

pharmacological treatments

non-pharmacological interventions

differential diagnoses