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Audio-Digest FoundationFamily Practice


Volume 56, Issue 28
July 28, 2008

The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program. If, after reviewing the summary, you would like to hear the contents and earn CME/CE credit, simply use your browser's back button to return to the order page and add this program to your cart. You will receive by mail the one-hour audiocassette or audio CD, a hard copy of the written summary (including a 10-question test), and a CME/CE response form.

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processes); brain injury and neurologic disorders—injury to medial frontal area may cause apathetic syndromes; strokes that affect frontal area often associated with depression; other patterns of behavior (eg, disinhibition, mania) associated with other injuries and disorders; early life experiences—traumatic experiences at young age may lead to neural changes and increased susceptibility to psychiatric disorders; interaction—relationships among internal and external factors and mood are complex; categorizing depression as “reactive” or “endogenous” too simplistic
Active listening: “listen with two ears”; diagnostic—recognize signs and symptoms that indicate treatable syndrome (eg, major depressive disorder); use diagnosis to guide management; empathetic—piece together narrative of life events and responses; identify underlying vulnerabilities and contributory circumstances; seek to understand patient as individual and reasons for current crisis
Diagnosis: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) lists signs and symptoms of depression (eg, sleep disturbance, loss of interest in activities, inappropriate guilt, loss of energy, mood changes, reduced concentration, changes in appetite, depressed psychomotor response, suicidality); depressive episode defined as 5 symptoms for 2 wk
Distinctive symptoms of major depression: melancholy—intractable and debilitating; diminished vital sense—decreased mental and physical potency; reduced zest for life and capacity for pleasure; diminished self-regard—decreased confidence and self-efficacy; increased “blameworthiness” and sensitivity to and preoccupation with errors; diurnal pattern of distress—symptoms worse in morning and improve throughout day; note, diurnal pattern of physical symptoms (eg, nausea and stomachache) also may indicate depression
Alcohol abuse or intoxication: always ask about alcohol use; patients may not volunteer information; simulates depression—contributes to mood instability; causes interval insomnia and disturbed continuity of sleep; affects appetite and mood; complicates depression—lowers threshold for self harm (intoxication increases likelihood of acting on suicidal thoughts); age of onset—alcohol abuse may begin late in life, often in association with stress specific to life phase (eg, ailing spouse)
Wish to hasten death: studies looking at terminally ill patients have found that patients wishing to hasten death also have symptoms of major depression; psychologic distress often more important factor than physical pain among people who ask for physician-assisted suicide (data from Oregon); anecdotal evidence suggests that terminally ill patients with concomitant major depression no longer wish to hasten death once depression treated
Assessment of suicide risk: among older individuals, depression most common reason for suicide; expressed intentions—important to ask about suicidal ideation or plans, but many suicidal patients deny intentions; mental status— high-risk findings include psychic pain, self-loathing, and hopelessness (“lethal triad”); other red flags include perturbation, delusions of guilt, hallucinations advising suicide, and passive wishes for death; history—patients with past attempts at suicide at highest risk; other red flags include history of acute demoralizing crisis and concurrent substance abuse
Expectant trust: conceptualized by Jerome Frank; patient perception that clinician cares, is competent and optimistic about outcome, and will not abandon patient; attitude inspires hope (important for treatment of depression and prevention of suicide)
Formulation of narrative: assess vulnerabilities (eg, personality traits, psychosocial circumstances, substance abuse), current stressors and life circumstances (eg, conjugal bereavement), and how these interact to create current crisis (eg, loneliness, suicidality); approach to treatment—leverage strengths to compensate for vulnerabilities and resolve crisis
Response to medical therapy: depression generally does not remit with first intervention; Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial looked at response to pharmacotherapy among 4000 outpatients (few exclusions; population representative of most practice settings); level 1—depression remitted in 30% of patients after first intervention (substantial trial with citalopram); level 2—for remaining patients, augmenting treatment with bupropion (eg, Wellbutrin) or buspirone (Buspar) resulted in remission in 30% of patients in each group; switching to sertraline (Zoloft), venlafaxine (Effexor), or bupropion resulted in remission in 18%, 25%, and 21%, respectively; level 3— augmenting treatment with lithium or triiodothyronine resulted in remission in 16% and 25% of patients in each group; switching to mirtazapine (Remeron) or nortriptyline resulted in remission in 12% and 20%, respectively; level 4— switching to monoamine oxidase inhibitor (MAOI) or combination of venlafaxine plus mirtazapine resulted in remission in 7% and 14%, respectively; overall results—remission achieved in 70% of patients; numerous extended trials often necessary
Maintenance pharmacotherapy: important, especially for older patients who respond to pharmacotherapy; randomized placebo-controlled study compared maintenance therapy to paroxetine (eg, Paxil) and psychotherapy; depression recurred less frequently (35%-37%) among patients treated with paroxetine (with or without psychotherapy), compared to those treated with psychotherapy or placebo alone (68% and 58%, respectively)
Electroconvulsive therapy (ECT): appropriate for patients unresponsive to pharmacotherapy and for those in imminent danger; single most effective treatment for acute episodes of major depression; usually well tolerated, even by very old patients; adverse effects—cardiovascular effects (eg, arrhythmias) relatively uncommon, and usually benign and manageable; cognitive effects (eg, memory loss) highly variable and not dependent on age; risk for adverse cognitive effects increases with number and frequency of treatments and bilateral (vs unilateral) electrostimulation; usually time-limited; effect—ECT interrupts depressive episode, but does not prevent relapse (therefore, additional treatment necessary); maintenance ECT—weekly, biweekly, or monthly sessions may be effective; interval shortened or extended as necessary to prevent recurrence of serious depression
Persistence and vigilance: critical; continuity of care and ongoing assessment of, eg, therapeutic response, adverse effects, emergent problems, necessary; important for clinician to remain supportive and optimistic
Questions and answers: treatment history—ask about efficacy and tolerability of previously used antidepressants; choice and dosing of antidepressants—speaker begins with low-dose selective serotonin reuptake inhibitor (SSRI; eg, citalopram 5 mg), then increases dose every week, as tolerated; if additional therapy needed once adequate dose reached, speaker adds buspirone (based on results from STAR*D trial)
DELIRIUM AND ALZHEIMER’S DISEASE —Joel D. Posner, MD, Professor of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY
Aging population: individuals \>65 yr of age represent 17% of population of United States; aging baby boomers (cohort of 80 million people) beginning to face age-related health issues
Delirium and dementia: often overlooked or minimized; delirium (acute; medical emergency) may occur in patients with baseline dementia, but may go unrecognized and untreated
Assessing mental status: baseline assessment required in order to recognize changes in mental status; Mini-Mental State Examination (MMSE) recommended annually (requires <10 min; may be performed by auxiliary staff); change in score indicates change in mental status; components of MMSE—orientation; registration; attention; calculations; recall; language; assessment of orientation normally made by asking about state and country; speaker prefers to ask questions about time, place (ie, setting), and person

Delirium
General: acute change in mental status; potentially life-threatening medical emergency; waxing and waning levels of consciousness distinguishes delirium from dementia (chronic; relatively stable); agitation and visual hallucinations also common
Reversible causes: mnemonic spells DEMENTIA
Drugs: prescription and over-the-counter (OTC) medications; sleep medications, psychiatric medications, anticholinergic agents (including OTC antihistamines), and others may cause acute confusion
Endocrine abnormalities: eg, hyperthyroidism and hypothyroidism associated with atypical signs in older adults
Metabolic causes: hypoxia (eg, during sleep, exercise, or normal activities); hypoglycemia; electrolyte imbalance (eg, diuretic use may result in hyponatremia, causing acute confusion and risk for death); impaired function of liver or kidneys
Ears, eyes, and emotions: impaired hearing or vision may increase confusion and lead to odd behaviors; depression may present as acute confusional state
Nutrition and normal-pressure hydrocephalus: deficiencies of vitamin B12 , folate, or thiamine may accompany alcohol abuse, and may represent medical emergency (parenteral supplementation required); identification of normal-pressure hydrocephalus has treatment implications for patients <75 yr of age
Takes up space in brain: eg, tumors, trauma, subdural hematoma
Infections: atypical presentations common among older adults
Arteries: anything that prevents oxygenated blood from reaching brain (eg, heart failure, cardiac arrhythmias); acute confusional state (without chest pain or shortness of breath) is presenting symptom of myocardial infarction in 25% of adults \>85 yr of age
Work-up: history and physical examination; MMSE or other assessment of mental status; laboratory tests—complete blood cell (CBC) count (detects severe anemia and evidence of infection); sedimentation rate (high rate may signal arteritis, especially when accompanied by acute confusion); thyroid function tests; electrolyte levels; renal function tests; blood glucose levels; vitamin B12 and folate levels (methylmalonic acid test for B12 ; homocysteine levels better indicator of folate status than serum level of folic acid; supplement empirically); other tests—electrocardiography; oximetry; chest x- ray; computed tomography (CT; identifies normal-pressure hydrocephalus); magnetic resonance imaging (MRI; visualizes old aneurysms not visible on CT); magnetic resonance arteriography (MRA; visualizes blood vessels)

Alzheimer’s Disease (AD)
Types of dementia: purely vascular (5%); vascular dementia plus AD (10%); AD alone (65%); AD plus Lewy body disease (5%; progresses relatively rapidly; marked by strange behavior)
Pathology: characterized by neurofibrillary tangles and amyloid plaques in brain; pathophysiology and treatment implications—amyloid plaques impair function of nerves, disturbing memory cognition and behavior; prevention of plaques may prevent progression of AD; current treatment based on cholinergic hypothesis (ie, low levels of acetylcholine results in diminished transmission of impulses across synapses)
Research: valsartan—prevents amyloid clumping in humans and blocks memory loss in rat models of AD; low-density lipoprotein receptor-related protein (LRP)—levels and potency reduced among patients with AD; exogenous LRP-4 clears amyloid- β in brains of humans and rats and prevents memory loss in rats; potential implications for treatment
Early signs of AD: 3 yr before diagnosis, 40% of patients experience social withdrawal; depression affects 60% of patients 2 yr before diagnosis; 20% of patients become paranoid 1.5 yr before diagnosis; importance of recognizing early signs—management implications; patient and families can make proper arrangements
Clinical ABCs: activities of daily living (ADLs); behavior; cognition; mild AD—problems with executing routine tasks; changes in behavior and personality; moderate degree of confusion and memory loss; moderate AD—patients require assistance with ADLs (eg, feeding, bathing, dressing) and may exhibit paranoia, insomnia, and anxiety; memory loss becomes more chronic; severe AD—characterized by speech loss, inability to recognize friends and family, and general loss of function
Treatment: current approach based on cholinergic mechanism; acetylcholinesterase breaks down acetylcholine; cholinesterase inhibitors inhibit action of acetylcholinesterase and increase levels of acetylcholine; adverse effects— gastrointestinal upset (sometimes severe); slow titration of medication necessary; donepezil—begin with 5 mg at bedtime; increase to 10 mg after 4 to 6 wk; rivastigmine—must be taken with food; begin with 1.5 mg bid; increase to 3 mg bid (minimum effective dose in most patients) after 4 wk; increase to 4.5 mg, then 6.0 mg (titrating every 4 wk), if tolerated; galantamine—must be taken with food; begin with 4 mg bid; increase by 4 mg every 4 wk, with maximum dose of 12 mg bid (use minimum effective dose); memantine—use in combination with other medications; after dose of primary medication stabilized, begin with 5 mg/day; increase to 5 mg bid, then add 5 mg/day in divided doses until maximum dose (10 mg, bid) reached
Efficacy: modest; patients taking donepezil or rivastigmine have improved cognitive performance, compared to those taking placebo; early initiation of treatment may improve results; little evidence of effect on ADLs or behavior

Suggested Reading

APA Work Group on Alzheimer’s Disease and other Dementias: American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry 164(12 Suppl):5, 2007; Caplan JP: Too much too soon? Refeeding syndrome as an iatrogenic cause of delirium. Psychosomatics 49:249, 2008; Feart C et al: Plasma eicosapentaenoic acid is inversely associated with severity of depressive symptomatology in the elderly: data from the Bordeaux sample of the Three-City Study. Am J Clin Nutr 87:1156, 2008; Feldman HH et al: Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 178:825, 2008; Grossman M et al: Longitudinal decline in autopsy-defined frontotemporal lobar degeneration. Neurology 70:2036, 2008; Heo M et al: Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050. Int J Geriatr Psychiatry May 23, 2008 [Epub ahead of print]; Hoogendijk WJ et al: Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry 65:508, 2008; Nelson JC et al: Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry May 12, 2008 [Epub ahead of print]; Niu K et al: Home blood pressure is associated with depressive symptoms in an elderly population aged 70 years and over: a population-based, cross-sectional analysis. Hypertens Res 31:409, 2008; Richard KL et al: Toll-like receptor 2 acts as natural innate immune receptor to clear amyloid beta 1-42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 70:2036, 2008; Sun X et al: amyloid-associated depression: a prodromal depression of Alzheimer disease? Arch Gen Psychiatry 65:542, 2008; Voelker R: Guideline: dementia drugs’ benefits uncertain. JAMA 299:1763, 2008; Wei LA et al: The Confusion Assessment Method: a systematic review of current usage. J Am Geriatr Soc 56:823, 2008; Wiesenfeld L: Delirium: the ADVISE approach and tips from the frontlines. Geriatrics 63:28, 2008.

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