Hello, my name is Raj Tempe, and I'm the past president of the American Association for Geriatric Psychiatry, and I'm going to talk to you about mood disorders among older adults. Disclosures, I have no conflicts of interest to disclose for this presentation. The agenda for today's talk is epidemiology and risk factors for mood disorders in late life, differential diagnosis of mood disorders in late life, workup of individuals with mood disorders in late life, a few important points regarding suicide in late life, and then a section on treatment of mood disorders in late life. Late life depression, epidemiology, and risk factors. Late life depression means the occurrence of depressive symptoms in individuals over 60 years in age. What we know is that individuals with late life depression have what is called depression without sadness. That means they have lack of feeling or emotion. They have more prominent cognitive complaints. They have more prominent somatic complaints. They have often unexplained health worries. They have heightened pain experiences or complaints, and they have multiple primary care visits without resolution of problem. These individuals also present with irritability, social withdrawal, and avoidance of social interactions. There is a prominent loss of interest and pleasure in activities. These individuals present with functional impairment or otherwise unexplained functional decline. Important point to remember, late life depression, more somatic and cognitive complaints, and less affective complaints. Epidemiology. Classic major depression is less common among older adults than in younger adults. The prevalence of major depressive disorder among older adults is about 1 to 3%, which is about a third of what you would find in younger adults, but they are higher in vulnerable subgroups of older adults, including medically hospitalized, where the prevalence is about 11%, and in long-term care facilities, where the prevalence of major depression is about 12%. The prevalence of symptoms is much higher than the prevalence of disorders among older adults. So, for example, in the general population, the prevalence of major depressive disorder is only about 2%, but depressive symptoms are present in 25 to 40% of individuals. In medical units, it's about 12% for major depression, and 30% have depressive symptoms. In nursing homes, the prevalence of major depressive disorder is about 10 to 12%, whereas depressive symptoms are present in 30 to 50% of the individuals. Biological risk factors for late life depression include female gender, neurotransmitter dysfunction, and serotonin, dopamine, and norepinephrine, endocrine changes, genetics, medical illness, comorbid psychiatric disorders, and microvascular disease, both peripheral and cerebral. Risk factors include medical illnesses, common illnesses that can cause depression in late life are cancers. The prevalence rate is about 25%, post-op depression greater than 25%, Alzheimer's disease about 33%, and Parkinson's disease about 50%. Depression and cerebrovascular disease. We now know that depression is independent risk factor for adverse cardiac events among older adults. It predicts poor cardiac prognosis in individuals already diagnosed with cardiovascular disease. Depression associated with a two to two and a half fold increase in impaired cardiovascular outcomes and mortality among individuals who are hospitalized for myocardial infarction. Available data indicates that 10 days post-MI, 45% of these individuals met the criteria for major or minor depression, and 18% met the criteria for major depressive disorder. Three to four months post-MI, 33% still met the criteria for depression, including 77% of those who previously met the criteria for major depressive disorder. So the comorbidity of depression and cardiovascular disease is very important, especially in late life. Depression and stroke. What we know is that depressed individuals have a 45% higher risk for stroke and 25% have higher risk of stroke related mortality. Post-stroke depression in these individuals present with major depressive disorder and up to 25% and minor depression in another 30%. The peak time for post-stroke depression is six months to two years post-stroke. These individuals often have a preexisting vascular depression diagnosis. They're also more common among women when compared to men. Relationship between depression and Parkinson's disease. Depression is highly prevalent among individuals with Parkinson's disease. The prevalence rates indicate about 43% of these individuals with Parkinson's disease have depression with the range between 25 and 70%. These individuals have increased risk of, they have a history of depression, which increases the risk of depression in late life with Parkinson's disease. They're usually associated with greater functional deficits. They're associated with decreased time to medication for motor symptoms. So the motor symptoms occur more frequently, even with adequate medication treatment. And this may be related to increased serotonin reuptake. Psychosocial risk factors for late life depression include personality traits, cognitive distortions, death of a spouse or a loved one, disability and functional decline, social isolation, location, caregiver burden, and socioeconomic status, with lower socioeconomic status increasing the risk for late life depression. Differential diagnosis include major depressive disorder, either single episode or recurrent, grief, bipolar disorder, depressive episode, psychotic depression, that is major depressive disorder, severe with psychosis, persistent depressive disorder, also known as dysthymia, adjustment disorder with depressed mood, depression associated with medical illnesses, namely cardiovascular, cerebrovascular, Alzheimer's disease, and Parkinson's disease, dementias associated with depression, and substance-related mood disorders. Major depressive disorder, the DSM-5 criteria are same for individuals regardless of their age. People need to meet five of the nine symptoms that are not directly related to a general medical, not directly related or attributable to a general medical condition. What are new for DSM-5 is that there is no bereavement exclusion. It removes the implication that grief only lasts for two months. It recognizes risk factors that precipitate major depressive episode, that means grief is a risk factor for major depressive episode. Depressive symptoms associated with bereavement respond to treatment. The provider has to exercise professional judgment as to whether someone with symptoms of major depressive disorder and who is in grief should be diagnosed with and treated for depression. Difference between depression or grief, major depressive disorder, these individuals usually have depressed mood. They have inability to anticipate pleasure or happiness. They present with pervasive unhappiness. They are self-critical, feel guilty and pessimistic. They feel worthless and have suicidal thoughts. Individuals with grief often present with predominant emptiness or sense of loss, which decreases in intensity days to week after the loss. These symptoms occur in waves. They may experience positive emotions or humor. Self-esteem is often preserved and morbid thoughts about joining the disease are present, but no active suicidal thoughts. Psychotic depression, individuals with late life depression may also present with psychotic features, which include delusions. They have fear of incurable illness and a focus on abdomen. They also have a fear of persecution. They feel severely guilty about trivial episodes from the past. They often present with feelings of worthlessness, psychomotor retardation, increased suicidal ideation, poor social supports, and these individuals do not often present with hallucinations. So delusions are present, but hallucinations are uncommon. Late life bipolar disorder, these individuals, older adults usually have bipolar disorder, but not as commonly as younger adults. The lifetime prevalence for bipolar disorder in the elderly is about 0.5% to 0.1%, which is about one-tenth what you would see in the younger adult population. Point prevalence is 0.1% to 0.5%, 10% to 25% of older adults with mood disorders present with bipolar disorder, 4% to 8% of admissions to inpatient geriatric psychiatric units are due to bipolar disorder. These individuals are at higher risk of developing dementia. The pooled odds ratio is 2.36, with the confidence interval being 1.36 to 4.09. Bipolar disorder may present with depressive or manic episodes, which may present with mixed features. The mania in the elderly usually presents with grandiosity or increased self-esteem, increased need for sleep, flight of ideas, talkativeness, psychomotor agitation, distractibility, spending sprees, dysmorphic mood, perseverative behavior, catatonia-like symptoms, and picking at imaginary objects. Early versus late onset bipolar disorder. So early onset bipolar disorder is those individuals who have bipolar symptoms before the, before 50 years of age. Late onset is those people who have symptoms after 50 years of age. Often the first presenting symptom in early onset bipolar disorder is mania or hypomania among older adults that is late onset greater than 50 years is depressive episodes. Manic episodes are more likely in early onset, less likely in late onset bipolar disorder. Dysmorphic symptoms are more likely among early onset bipolar disorder and less likely in late onset bipolar disorder. Latency between the first and second episodes is shorter in early onset bipolar disorder, but it's longer in late onset bipolar disorder. Family history is often present in early onset bipolar disorder, whereas it is less likely in late onset bipolar disorder. is usually absent in early onset bipolar disorder, but usually present in late onset bipolar disorder. Medical comorbidity is less likely in early onset bipolar disorder or more likely in late onset bipolar disorder. Psychiatric comorbidities are more likely in early onset bipolar disorder, less likely in late onset bipolar disorder. Cognitive dysfunction is less likely in early onset bipolar disorder, more likely in late onset bipolar disorder. Use of healthcare services is less in early onset bipolar disorder, but more in late onset bipolar disorder when compared to early onset bipolar disorder. Vascular depression is usually characterized by white matter lesions in the brain, executive dysfunction, and onset late in life. Other clinical symptoms include psychomotor retardation, apathy, poor insight, excess disability, and these individuals often have limited depressive ideation, but more limited depressive ideation, more agitation, and guilt. Vascular depression, epidemiology, it is seen in 3.4% of individuals greater than 50 years in age, and it is seen in 22% of individuals with a lifetime major depressive disorder. Risk factors for vascular depression are older age, presence of hypertension, diabetes, hyperlipidemia, smoking, and coronary artery disease, and these individuals often respond poorly to antidepressant medications. Those mechanisms are twofold. One could be because of a small direct lesion that might disrupt frontal subcortical white matter tracts that underlie emotion and cognition, so one small lesion causing a significant disruption in the white matter tracts, or it could be because of an accumulation of lesions that could eventually reach a threshold level, perhaps then conferring a predisposition for depression. So these are individuals who have chronic white matter changes, then after a certain stage when the white matter lesions go beyond a certain point, individuals would start presenting with depressive symptoms. This is the image of individuals with small white matter ischemic changes, as you can clearly see, and these are individuals who may present with vascular depression. Depression and vascular dementia, two studies have evaluated this. The first one is the British study, which was a 25-year follow-up of older adults with depression versus controls. Fourteen percent of depressed patients and no control subjects developed dementia at follow-up. Vascular dementia was the most common type of dementia noted in these individuals. The French Personae studies, the Parkwood study, which was a subgroup of men on whom vascular disease led to depressive symptoms, depression later progressed to dementia. The odds ratio among men was 3.5, whereas the odds ratio among women was 1.2, with the p-value for sex difference being statistically significant at 0.03. Depression-associated dementia, it is most commonly seen among late-onset depression. A large proportion of these individuals are left with cognitive impairment even after the depressive symptoms remit. Forty percent of these individuals with the so-called reversible dementia associated with depression develop irreversible dementia within three years of the depressive episode. This is a table which differentiates depression-associated dementia with primary dementia. In depression-associated dementia, the onset is acute, whereas in primary dementia the onset is insidious. Past affective episodes are present in depressive-associated dementia, uncommon among primary dementia. Guilt and self-reproach are more common in depression-associated dementia, whereas they are uncommon in primary dementia. Diurnal variation is in mood, where the symptoms are worse in the morning, is seen in depression-associated dementia, whereas in primary dementia they're not seen. Memory deficits in depression-associated dementia, these individuals have registration and recall which is impaired, whereas their remote memory may be better than recent memory. Registration is better than recall among primary dementia, whereas recent memory is worse than remote memory early in the illness. Response to cognitive testing in depression-associated dementia, these individuals present with poor interest, and they often say, do not know, when you ask questions, whereas in individuals with primary dementia, unless they're severely demented, effort and interest are often normal. Reaction to mistakes among depression-associated dementia individuals, they tend to give up easily, whereas in primary dementia, unless the patient is severely demented, they tend to confabulate and make up information. Practice effect among depression-associated dementia can easily be coached, so people after multiple attempts do better, whereas among individuals with primary dementia, they cannot be coached. In response to sleep deprivation, depression-associated dementia, these deficits may improve, that is, up to 24 hours of sleep deprivation, whereas in primary dementia, if they have sleep deprivation, their cognitive function continue to worsen. Depression and Alzheimer's disease, we now know that depression is an independent risk factor for Alzheimer's disease, rather than just being a prodrome. Systematic review and meta-analysis on the relation between depression and dementia, which was studied by Owen B. and colleagues, found that the pool odds ratio for risk for dementia with a history of depression was 2.03 in case control studies, whereas it was 1.90 in the cohort studies. Interval between the diagnosis of depression and Alzheimer's disease positively correlated to an increased risk of dementia, so if the episode is closer together, the diagnosis often happens sooner. Important mood-related substances, we know that individuals can present with mood disorders related to substances. The common substances are depressants, alcohol, barbiturates, and benzodiazepines, whereas those substances that can cause mania include cocaine, amphetamine, alcohol, hallucinogen, PCP, antidepressants, dopamine agonists, decongestants, steroids, immunosuppressants, and certain chemotherapeutic agents. Workup for individuals with mood disorders in late life. Workup includes history, screening exam, physical examination, laboratory tests, polysomnography, and MRI of the brain. In history, we often ask about the duration of the current episode, current symptoms, and severity of symptoms, their impact on functioning, history of previous episodes of mood disorders, substance abuse history, response to previous treatments, family history of depression, suicide, alcohol abuse, psychosocial context and stressors, and collateral from family and caregivers to know the level of functioning and the history of the individual. These are the common scales that we use to assess depression in late life. These include the Geriatric Depression Scale, the Cornell Scale for Depression and Dementia, Brief Assessment Schedule Depression Cards, Center for Epidemiological Studies Depression Scale, the Hamilton Rating Scale for Depression, the Montgomery Asperger Rating Depression Scale, Zung Self Rating Depression Scale, Geriatric Mental Health State Schedule, Clinician's Global Impression of Change, Brief Psychiatric Rating Scale, and the General Health Questionnaire. Among these, the Geriatric Depression Scale is the one that is most commonly used in clinic and among the randomized controlled trials. It's usually the Hamilton Depression Rating Scale or the Montgomery Asperger Depression Rating Scale that is commonly used. I use the Depression Rating Scale for my older adult patients in the clinic. Physical examination, we look for weight loss in these individuals because many of the older adults with depression are present with weight loss. We look for pulmonary symptoms that can cause, you know, depression. We look for cardiac disease as this can lead to depression. We also look for neurological symptoms, including laterality, which is caused by vascular disease as vascular depression is common among older adults. And we look for rigidity, which rules out Parkinson's disease because individuals with Parkinson's disease are at higher risk for developing depression in late life. Lab workup, lab workup. So we check for thyrotannin, CBC, vitamin B12, folate. We look for EKG, look for cardiovascular problems. We look for bradycardia, QTC prolongation. We do polysomnography to look for persistent sleep abnormalities. We like to rule out sleep apnea. And when we get an MRI of the brain, we look for vascular changes of the brain to rule out vascular dementia. We know that the rates of suicides are increasing over time. The rate in adults less than, greater than 65 years in age is 16.6 per 100,000 when compared to 13.4 in the 100,000 population. So older adults are overrepresented among individuals who commit suicide. The highest risk group for suicide is the white, are white men who are 85 years and older. In 2016, the rate of suicide among white men over the age of 85 was 52.5% per 100,000 when compared to white women greater than 85 years in age, where their rates were 3.45 per 100,000. The highest risk, commonest group that commits suicide in old age is white men who are 85 years and older. Risk factors for suicide, highest risk among all illnesses is bipolar disorder. The odds ratio is 9.2, followed by severe pain, depression, psychotic disorders, anxiety disorders, seizure disorders, urinary incontinence, COPD, and moderate pain. Older adults who commit suicide often have a history of suicide attempt. They often have alcohol dependence or abuse as a comorbid diagnosis. There is usually availability of firearms for these individuals. They have higher levels of neuroticism and lower scores for openness to experience and have restricted range of interests. These individuals also have increased physical ability and social isolation. Treatments. Aims for treatment of late life depression include reducing symptoms, preventing suicidal ideation and plan, preventing relapses or recurrence of symptoms, improving cognition and function, and helping older adults develop coping skills. Treatment methods include treating the underlying factors, including medications, drugs of abuse, alcohol, comorbid illness, et cetera, using antidepressants and augmenting agents, psychotherapy, combination treatment of antidepressants and psychotherapy, and electroconvulsive therapy. Antidepressants, Taylor and Doraiswamy in their 2004 study found that individuals with late-life depression respond equally to different classes of medications. 71.5% of the trials reported significant greater efficacy for drug when compared to placebo. There were no significant differences between active agents, but majority of the studies were underpowered to detect a difference. These antidepressants were well-tolerated with no serious adverse effects. When combining all antidepressant trials, the number needed to treat to get a 50% or greater reduction in HAMD was eight, whereas the number needed to get an improvement on the clinical global impression was a seven, showing that antidepressants are as effective among older adults with late-life depression when compared to younger adults with depression. Nelson and Delucci and Schneider in their meta-analysis, which included 10 unique trials of 13 different antidepressants, found that the odds ratio for response was 1.40, and the odds ratio for remission was 1.27. The mean pool response rate for antidepressants among older adults was 44.4 when compared to placebo, which was 34.7. The odds ratio for response, as expected, was significantly higher in the 10- to 12-week trials, odds ratio of 1.73, when compared to the 6- to 8-week trials where the odds ratio was 1.22, indicating that older adults with depression should have longer trials than younger adults with depression to get a higher response and remission rates. Increased odds ratio for discontinuation of medication was 1.22, with a p-value of 0.005, indicating that antidepressants do cause more side effects than placebo among individuals with late-life depression. We did a study in 2009 where we looked at antidepressants with multiple actions versus single-action antidepressants where we compared relative efficacy and tolerability of SSRIs, tricyclics, and SNRIs. We found two head-to-head trials of tricyclics where tricyclics and SSRIs had comparable efficacy. Data from five studies suggested no additional efficacy benefit for SNRIs when the vaccine compared with SSRIs or TCAs. This study suggested that dual-action antidepressants, that is the TCAs and SNRIs, do not confer any additional benefits and efficacy over single-action agents, which is the SSRIs, in the treatment of depression among older adults. This is a major study done by Chip Reynolds, Du, and Pollack. They compared the use of paroxetine among older adults with depression. Paroxetine or placebo were combined with either monthly psychotherapy or clinical management sessions. When they looked at recurrence rate of major depression after two years, 35% of individuals on paroxetine plus psychotherapy had a recurrence of symptoms after two years when compared to 37% of individuals who were on paroxetine plus clinical management sessions when compared to 68% of individuals on placebo and psychotherapy and 58% of individuals on placebo with clinical management sessions. After adjustment for effect of therapy, the relative risk of recurrence among the placebo group was 2.4 times more than what was in the paroxetine group, and the number needed to prevent recurrences was 4, indicating that individuals with late-life depression should continue on antidepressants or the risk of relapse and recurrence is high. Psychotic depression, there were three major trials that were done for the treatment of psychotic depression in late life. In the first trial by Ben Malson and colleagues, nortriptyline and placebo was found to be inferior to nortriptyline plus perfenazine. The response rate was 44% versus 50%. Extrapyramidal symptoms scores, as expected, sorry, extrapyramidal symptoms, surprisingly, were not significantly greater between the two treatment groups despite using an older antipsychotic like perfenazine. In Myers et al's study in 2009, the investigators combined olanzapine plus sertraline when compared to olanzapine or placebo groups. What the investigators found was that the odds ratio for response was 1.28. So people on olanzapine plus sertraline did better. Remission rate was 41.9% versus 23.9% in favor of the olanzapine-sertraline group. The investigators found that there was increased cholesterol and triglycerides in both groups. Increased glucose was seen mainly among the younger adult population and significantly more weight gain was seen in younger adults compared to the older adult population, indicating that olanzapine-sertraline group was better at treating psychotic depression with no significant changes when compared to younger adults for side effects. In the study by Blumberger et al, the investigators found that better response to psychotic depression was seen in individuals who had no previous treatment or inadequate treatment. Poor response was seen if they had failed monotherapy or a combination of antidepressant plus antipsychotic medication among older adults with psychotic depression. Jurlic and colleagues in that 2006 paper studied the risk of suicide among individuals prescribed antidepressants. The investigators found that during the first month of therapy, SSRI antidepressants were associated with nearly five-fold higher risk of completed suicide when compared to other antidepressants. The investigators also found that the risk was independent of a recent diagnosis of depression or the receipt of psychiatric care. Suicides of a violent nature were more common among individuals who were prescribed SSRI treatment. There was no disproportionate suicide risk increase seen during the second and the subsequent months compared to the first month. The absolute risk of suicide with all antidepressants was found to be low in this study. Psychopharmacological treatment strategies are based upon the past history and treatment history. Also, we look at family history, including treatments. We look at suicidality. We look for symptoms like insomnia, anxiety, and psychosis. We look for comorbid substance use, especially alcohol. We look for comorbid medical illnesses, current medications that are being prescribed, and we also look for cognitive functioning of the individual. Psychopharmacological treatment strategies can be tailored depending upon the individual's symptoms. So for an individual who presents with anxious depression, SSRIs would be your first-line treatment. In individuals who present with unmotivated or apathetic depression, bupropion would be your first-line treatment. Individuals who are present with sleep and appetite disturbance, along with other depressive symptoms, mirtazapine would be your first-line treatment, and individuals who are present with chronic pain, duloxetine, or venlafaxine would be your first-line treatment. Now, you can tailor your treatment based on the side effect profile of the drug. If individuals who have weight gain issues, bupropion can be used as it causes minimal weight gain. For individuals who have sexual side effects or sexual dysfunction, bupropion or mirtazapine would be your preferred drug. For individuals who are on multiple different medications, citalopram, escitalopram, sertraline, venlafaxine, and mirtazapine would be your drug's use as they have minimal drug-drug interactions. Initial dosages among late-life depression, the usual rule of thumb is cut the dose by half of what you would give to an older adult. Start low, go slow, but keep on going. We need about 8 to 12 weeks for the full response of the antidepressants to be realized. If the individual does not respond to the maximally tolerated dose of a medication for 4 weeks, the chances of response after that is highly unlikely, so it is better to either augment or switch treatments. Augmentation strategies, two main strategies have been tried. The first one is using lithium. There are more positive results in case series and retrospective studies when compared to prospective studies where the response rate was only 20 to 24%. The study of augmentation with antipsychotic medications is mainly those individuals have been studied with adipropasol, where the odds ratio of response was about 2.0 with a p-value of 0.03, which is statistically significant. The rates of akathisia and parkinsonism, as expected, were more in the individuals who were augmented with adipropasol. This augmentation strategy was efficacious even among individuals who had failed to remit to symptoms with two or more antidepressant trials, including the trial of venlafaxine. So, again, adipropasol may be a good augmenting agent along with lithium among older adults. Now, what about the evidence for, you know, newer antidepressants? The study by Patel et al. found no published data supporting the use of antidepressants like velazodone, levomilnasopran, or brexipropasol among older adults with depression. There was one randomized controlled trial each for the use of vortioxetine, butypine monotherapy, adipropasol augmentation, and methylphenidate augmentation among late-life depression individuals. Augmentation strategies, two major trials, one by White et al. and the other one by Leveritsky. In the first study by Ellen White and colleagues, these depressed individuals who were older, they were given bupropion SR, lithium, or nortriptyline, or they were switched to venlafaxine XR for individuals who had not responded to treatment with 12 weeks of paroxetine or had relapsed following treatment. These individuals were initially given paroxetine and interpersonal psychotherapy. What the investigators noted was that 51% discontinued augmentation due to side effects, with the bupropion group having the highest rate of side effects, and sequential treatment trials resulted in a cumulative response of 60%. Important point to remember, people, older adults with depression can be augmented with different agents. Side effect profiles are usually slightly higher in these individuals, like in the bupropion group, but sequential treatment will produce better response. So the important point is don't stop the trials, keep on trying different medications as augmentation strategies or switching strategies among individuals with late-life depression. The study by Helen Leveritsky and colleagues, the investigators used methylphenidase as the augmenting agent. It was a randomized double-blind placebo-controlled trial of methylphenidate, citalopram, or a combination of methylphenidate and citalopram. The daily dosing of citalopram was between 20 and 60 mg, with a mean of 32 mg a day. The methylphenidate dosing was 5 to 40 mg a day, with a mean of 16 mg a day. Methylphenidate plus citalopram group showed enhanced clinical response, both in HAMD and CGI, especially in the first four weeks of treatment. The side effect profile for individuals taking methylphenidate versus citalopram, versus the combination of methylphenidate and citalopram, was not significantly different, indicating that the medication combination was well-tolerated. Psychotherapy. Available evidence indicates that cognitive behavior therapy, interpersonal therapy, and problem-solving therapy are all highly beneficial among older adults. In one study of 1,600 approved primary care patients who were older, they preferred counseling, 57%, compared to medication, 43%. Medication preference was predicted by male gender and major depressive disorder versus dysthymia. Psychotherapy. There is evidence for problem-solving therapy, cognitive behavior therapy, and interpersonal therapy. The IMPACT trial, which was a collaborative care trial with problem-solving therapy, showed significant improvements among community-dwelling elderly who received psychotherapy for 12 months. At 12 weeks, problem-solving therapy was better than supportive in individuals with depression and executive dysfunction. In a Cochrane review, which included five trials with 153 participants, behavior therapy was superior to wait-list controls. In three trials that compared CBT to interpersonal therapy, there was no difference. Another trial found that nortriptyline plus interpersonal therapy was better than nortriptyline alone, was better than interpersonal therapy, was better than placebo, indicating combination of psychotherapy plus medication is better than either active treatment alone or better than placebo. Psychosocial interventions. Clinical case management has been found to be effective for the treatment of late-life depression among low-income elderly. The depression care pathway for patients at home, depression care pathway trial, showed that home health care nurses delivering depression care management in the patient's home was effective. Clinical benefits were seen among individuals who had moderate to severe depression, again indicating that psychosocial interventions are quite effective among late-life depression individuals. ECT, very, very important slide. ECT is considered first-line treatment for older adults with depression, pregnant women with depression, physically debilitated individuals with depression, individuals with depression and catatonia, and individuals with severe psychotic depression. Medical conditions that are associated with substantial risk when using ECT. Remember, there are no absolute contraindications for ECT. These are all relative contraindications. Space-occupying lesions, recent myocardial infarction, recent CVA, unstable aneurysm, pheochromocytoma, congestive heart failure, severe valvular disease and unstable angina, severe pulmonary disease, and cochlear implants. There is a boxed warning by the FDA for cochlear implants and ECT. What we use in older adults with depression is ultra-brief pulse right unilateral treatment at six times the seizure threshold. Modified ECT uses different anesthesia. Sedative is methohexatol, and the neuromuscular blocking agent is succinylcholine. This is what is usually used in the treatment of late-life depression using ECT. Next slide. Basics of ECT. Unilateral treatment is better than bilateral treatment for short-term treatments, that is five treatments or less. Three times a week ECT is better than once-a-week treatment. Response rates with ECT are between 55% and 84%. Relapse rates after stopping ECT are between 25% and 67%. Physical illnesses and higher frequency of preceding depressive episodes of longer duration were poor predictors of response to ECT among older adults. There is no evidence yet from follow-up studies for ECT causing significant cognitive deficits directly after treatment, one and three years follow-up period. Bilateral treatments often cause more increased inter-rectal confusion, especially in individuals who have white matter lesions in the brain and dementia. Cardiac side effects are more common in individuals with premorbid cardiac disease. Mortality figures are difficult to interpret due to lack of information on pretreatment illness, but overall ECT is a very safe treatment for late-life depression. Esketamine has been tried among older adults with depression. In one phase three study by Osh Ross et al, the individuals were randomized to receive one-to-one flexible dose esketamine nasal spray or the new oral antidepressant, that is esketamine plus antidepressant, or the new oral antidepressant and placebo nasal spray. So one-to-one of combination of antidepressant plus esketamine and placebo plus the new oral antidepressant. The main scale was the change in the Montgomery Aspergh Depression Rating Scale on the Madras from baseline to day 28. The investigators found that esketamine and antidepressant combination did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen in individuals who were 65 to 75 years old, and those individuals who had depression before the age of 55 years. But the important point is that esketamine was well tolerated in this study. So new trials or more trials are needed for esketamine among late-life depression to really see if this is a beneficial treatment that we can use for older adults with depression. Treatment of bipolar disorder among older adults, there are no specific guidelines to follow. Lithium has the most amount of data in the treatment of late-life bipolar disorder, followed by anticonvulsant mood stabilizers, followed by antipsychotics. Antidepressants are often helpful for comorbid conditions, but not directly for the treatment of bipolar depression. Benzodiazepines have very limited benefits in the treatment of individuals with bipolar disorder in late life. But if people have comorbid anxiety, it may be beneficial. But remember the side effect profile of benzodiazepines before you prescribe it. ECT is very helpful in individuals who have refractory bipolar disorder in late life. As stated earlier, electroconvulsive therapy is very helpful in individuals who have partial response to medications and individuals who have refractory psychotic depression or catasonic symptoms or individuals who have refractory suicidal or homicidal ideation. As we saw in the preceding slides, side effect profiles are slightly higher among the older adults. Unilateral and bilateral treatments are equally effective, but unilateral treatment is the initial course as it has less side effects than the bilateral treatment. Psychosocial therapies should always be added to pharmacotherapy or ECT as individuals with late life bipolar disorder will often have many psychosocial issues. So combined psychosocial treatments with medication treatments or ECT in late life bipolar disorder. In summary, mood disorders among older adults are not uncommon. Symptoms of mood disorders are more prevalent than specific disorders. Comorbid medical conditions, psychosocial stresses do affect the presentation and treatment for late life mood disorders. Psychopharmacology, psychotherapy, and ECT are all effective treatments for both depression and bipolar disorder in late life. Treatment strategies must be tailored to the patient's history. Symptom profile, comorbid medical illnesses, and medications, along with susceptibility to side effects, and of course, the preference of what the individual wants for treatment. Now, four questions and answers. Which of the following is commonly seen among individuals with late life depression? Prominent cognitive complaints, prominent somatic complaints, unexplained health worries, or all of the above? And the answer is all of the above. Remember, individuals with late life depression present with more somatic, cognitive, and health worries rather than more depressive symptoms. Which of the following is not commonly seen among older individuals with psychotic depression? Worthlessness, psychomotor retardation, hallucinations, suicidal ideation. The answer is, sorry, the answer is actually hallucinations. These individuals present with more worthlessness, psychomotor retardation, suicidal ideation, delusions than hallucinations. Which of the following disorders is associated with highest risk for suicide among older adults? Bipolar disorder, anxiety disorders, depressive disorders, psychotic disorders. And the answer is bipolar disorder. Remember the slide on risk factors. Bipolar disorder has the highest risk of suicide among older adults with an odds ratio of about nine when compared to individuals who do not have bipolar disorder. Which of the following is more likely to be seen among older adults with bipolar disorder when compared to younger adults with bipolar disorder? Manic episodes, psychotic symptoms, family history, cerebrovascular disease. The answer is cerebrovascular disease. Manic episodes, psychotic symptoms, and family history are more seen in younger onset bipolar disorders, whereas cerebrovascular disease is seen more among older adults with bipolar disorder. Thank you very much for listening to this lecture.

mood disorders

older adults

late-life depression

epidemiology

risk factors

symptoms prevalence

biological risk factors

depression and cardiovascular disease

treatment options