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DEPRESSION AND OTHER MOOD DISORDERS (Bipolar) in the Elderly S t e v e n Ta m , M D , U C I G e r i a t r i c s 2 OBJECTIVES Know and understand: • Incidence and morbidity of depressive disorders among older adults • Diagnostic criteria for depression and mania • Treatment options for older adults with depression or mania • Actions and side effects of drugs for depression and mania in older adults 3 TO P I C S C O V E R E D • Epidemiology • Diagnosis • Clinical Course • Suicide • Treatment: Psychotherapy, Drugs, ECT • Managing Non-response • Treating Bipolar Disorder Case Presentation • Geriatrics Eval: 75 year old female, resident of Blythe, previously independent and healthy, presented with daughter with concerns about changes in her cognition (inattentiveness, spotty short term memory, some repetitiveness) • Also with sadness, social withdrawal, decreased appetite and 10 pound weight loss in the past 6 months or so • Previously independent, loved working on her large yard – no longer doing now. No interest, also complains of fatigue no energy to do anything Case Presentation • Additionally had thoughts that the world was coming to an end soon, persistent. • Denied any suicidal thoughts • No significant PMHx (-HTN, DM, CAD, Stroke, CKD, hypo thyroid) • No alcohol/drugs • Widowed x 2 years • Son and daughter about an hour away • Stable vitals, and non-revealing physical exam • MMSE -4 on orientation, -2 on recall, -3 on attention 21/30 Sentence “The end is near.” EPIDEMIOLOGY AMONG O L D E R A D U LT S • Minor depression 15% of older people Causes use of health services, excess disability, poor health outcomes, including mortality • Major depression 6%–10% of older adults in primary care clinics 12%–20% of nursing home residents 11%–45% of hospitalized older adults • Bipolar disorder Remains a common diagnosis among aged psychiatric patients; does not “burn out” in old age 6 D S M- I V D I A G N O S T I C C R I T E R I A FOR MAJOR DEPRESSION • Gateway symptoms (must have 1) Depressed mood Loss of interest or pleasure (anhedonia) • Other symptoms Appetite change or weight loss Insomnia or hypersomnia Psychomotor agitation or retardation Loss of energy Feelings of worthlessness or guilt Difficulty concentrating, making decisions Recurrent thoughts of suicide or death 7 DSM-V • New depressive disorders for classification (disruptive mood dysregulation disorder and premenstrual dysphoric disorder) – Dysthymia now under category of persistent depressive disorder (includes chronic major depressive disorder); 2 years • No change in required symptoms, nor duration • Bereavement exclusion (2 months) removed 9 SCREENING (1 of 4) Geriatric Depression Scale (GDS) • Yes/No format • Lacks suicidal ideation query • Not useful for assessing treatment response • Not reliable in patients with moderate or severe dementia GDS • • • • Are you basically satisfied with your life? Do you often get bored? Do you often feel helpless? Do you prefer to stay at home rather than going out and doing new things? • Do you feel pretty worthless the way you are now? • 2/5 suggest the diagnosis of depression 11 SCREENING (2 of 4) 9-Item Patient Health Questionnaire (PHQ-9) • 9 items cover diagnostic criteria for major depression • Initial 2 questions can be used for screening • Serial administrations can be used to reliably assess response to treatment • Not reliable in patients with moderate to severe dementia 13 SCREENING (3 of 4) PHQ-9 score Depression severity Clinician response 1–4 None None 5–9 Mild to moderate If not currently treated, rescreen in 2 weeks. If currently treated, optimize antidepressant and rescreen in 2 weeks 10–14 Major depressive disorder Start antidepressant therapy ≥15 Major depressive disorder Start antidepressant therapy; obtain psychiatric consultation if suicidality or psychosis suspected 14 SCREENING (4 of 4) Prescriber response guidelines at 4 weeks based on PHQ-9 and sequenced treatment alternatives PHQ-9 score or change Outcome Clinician response 1–4 Nonresponse Switch medication Decrease of 2–4 points Partial response Add medication Decrease of ≥5 points Response Maintain medication Score <5 Remission Maintain medication D I A G N O S I S I N O L D E R PAT I E N T S I S D I F F I C U LT B E C A U S E T H E Y . . . • More often report somatic symptoms • Less often report depressed mood, guilt • May present with “masked” depression cloaked in preoccupation with physical concerns and complicated by overlap of physical and emotional symptoms 15 DIAGNOSTIC CHALLENGES IN MEDICAL SETTINGS • Symptoms of depressive and physical disorders often overlap, for example: Fatigue Disturbed sleep Diminished appetite • Seriously ill or disabled people may focus on thoughts of death or worthlessness, but not suicide • Side effects of drugs for other illnesses may be confused with depressive symptoms 16 HALLMARKS OF PSYCHOTIC DEPRESSION • Patients have sustained paranoid, guilty, or somatic delusions (plausible but inexplicably irrational beliefs) • Among older patients, most commonly seen in those needing inpatient psychiatric care • In primary care, may be seen when patients exhibit unwarranted suspicions, somatic symptoms, or physical preoccupations 17 18 DIFFERENTIAL DIAGNOSIS • Medical illness can mimic depression Thyroid disease Conditions that promote apathy • Dementia has overlapping symptoms Impaired concentration or sleep Lack of motivation, loss of interest, apathy Psychomotor retardation Sleep disturbance • Bereavement is different because: Most disturbing symptoms resolve in 2 months Not associated with marked functional impairment CLINICAL COURSE IN MAJOR DEPRESSION Recurrence, partial recovery, and chronicity . . . disability use of health care resources morbidity and mortality suicide 19 20 O L D E R A D U LT S A N D S U I C I D E • Older age is associated with increasing risk of suicide • One fourth of all suicides occur in people 65 • Risk factors: depression, physical illness, living alone, male gender, alcoholism • Violent suicides (eg, firearms, hanging) are more common than nonviolent methods among older adults, despite the potential for drug overdosing 21 S T E P S I N T R E AT I N G D E P R E S S I O N • Acute: reverse current episode • Continuation: prevent a relapse Continue for 6 months • Prophylaxis or maintenance: prevent recurrence Continue for 3 years or longer TYPES OF THERAPY FOR DEPRESSION • Psychotherapy • Pharmacotherapy • Electroconvulsive therapy (ECT) 22 23 PSYCHOTHERAPY • Individualize standard approaches Cognitive-behavioral therapy Interpersonal psychotherapy Problem-solving therapy • Combine with an antidepressant (has been shown to extend remission after recovery) • Watch for depressive syndromes in caregivers, who might benefit from therapy 24 PHARMACOTHERAPY Individualize choice of drug on basis of: • Patient’s comorbidities • Drug’s side-effect profile • Patient’s sensitivity to these effects • Drug’s potential for interacting with other medications 25 ANTIDEPRESSANTS • Selective serotonin-reuptake inhibitors (SSRIs) and selective serotonergic and noradrenergic reuptake inhibitors (SSRI/SNRI) • Tricyclic antidepressants (TCAs) • Others: bupropion, mirtazapine, MAOIs, methylphenidate S E L E C T I V E S E R O TO N I N - R E U P TA K E I N H I B I TO R S ( S S R I s ) 26 • Citalopram, escitalopram, fluoxetine, paroxetine, sertraline • For mild to moderately severe depression • Side effects: Anxiety, agitation, nausea & diarrhea, sexual effects, pseudoparkinsonism, warfarin effect, other drug interactions, hyponatremia/SIADH Falls and fractures in nursing-home patients Higher doses of citalopram with FDA warning of cardiac events (prolonged QT interval) TRICYCLIC ANTIDEPRESSANTS (TCAs) • Secondary amine TCAs most appropriate for older patients are nortriptyline and desipramine • For severe depression with melancholic features • Avoid in the presence of conduction disturbance, heart disease, intolerance to anticholinergic side effects 27 28 BUPROPION • Generally safe & well tolerated • activity of dopamine & norepinephrine • Side effects: Insomnia, anxiety, tremor, myoclonus Associated with 0.4% risk of seizures • Dose range: 150–300 mg/day 29 S S R I / S N R I : V E N L A FA X I N E • Acts as SSRI at low doses; at higher doses SNRI • Effective for major depression & generalized anxiety • Side effects: Nausea Hypertension Sexual dysfunction • Dose range: 75–300 mg/day 30 S S R I / S N R I : D E S V E N L A FA X I N E • Active metabolite of venlafaxine • Side effects: Nausea Headache Hypertension • Dose range 25–50 mg/day 31 SSRI/SNRI: DULOXETINE • Equally SSRI and SNRI • Effective for major depression and FDA-approved for neuropathic pain • Precautions: drug interactions (CYP450 1A2, 2D6 substrate), chronic liver disease, alcoholism, serum transaminase elevation • Dose range: 20–60 mg/day 32 M I R TA Z A P I N E • Norepinephrine, 5-HT2 , and 5-HT3 antagonist • Associated with weight gain, increased appetite • May be used for nursing-home residents with depression & dementia, nighttime agitation, weight loss • Dose range: 15–45 mg/day • May be given as single bedtime dose (sedative side effects) 33 M O N O A M I N E O X I D A S E I N H I B I TO R S (MAOIs) • Use if patient is resistant to other antidepressants • Side effects: Orthostatic hypotension, falls Life-threatening hypertensive crisis if taken with tyramine-rich foods, cold remedies (pressor amine) Fatal serotonin syndrome possible if taken with SSRI, meperidine 34 M E T H Y L P H E N I D AT E • No controlled data demonstrating efficacy for depression • Has been used for decades to treat major depression • May have role in reversing apathy, lack of energy in patients with dementia or disabling medical conditions 35 PHARMACOLOGIC ALGORITHM Initiate citalopram, escitalopram, or sertraline If response is inadequate, switch to paroxetine or fluoxetine, OR switch class based on symptom profile: Apathy, retardation Insomnia, anxiety, anorexia Pain Atypical, melancholic, anxious Bupropion Mirtazapine Duloxetine Venlafaxine If response is inadequate: Atypical Melancholic, anxious MAOI TCA 36 R E A S O N S TO U S E E C T • Effective for treatment of major depression & mania • First-line treatment for patients at serious risk for suicide, life-threatening poor intake • Standard for psychotic depression in older adults; response rates exceed 80% 37 COGNITIVE SIDE EFFECTS OF ECT • Anterograde amnesia improves rapidly after treatment • Retrograde amnesia is more persistent; recall of events just before treatment may be lost permanently • Lasting effects not shown in longitudinal studies • Right unilateral treatment: fewer side effects but less effective than bilateral 38 USING ECT • Contraindications are few: Increased intracranial pressure Recent MI or CVA and unstable CAD increase risk of complications • Continue pharmacotherapy following completion of ECT treatment • May use maintenance ECT to prevent relapse 39 INCIDENCE OF RESPONSE • 40% of pts with major depression respond to initial pharmacotherapy within 6 weeks • Additional 15%25% achieve remission with continued treatment for 6 weeks Monotherapy fails 35%45% Responsive to initial pharmacotherapy 40% Responsive to continued treatment 15%25% MANAGING NONRESPONSE AND PA R T I A L R E S P O N S E • The most common prescribing error is failure to increase the dose to the recommended level within the first 2 weeks of treatment • When monotherapy fails: Consider switch to another SSRI or other drug class Add another drug if response is partial despite adequate dose and duration of treatment Combine lithium carbonate, methylphenidate, or triiodothyronine with secondary amine TCA Add psychotherapy Consult a geriatric psychiatrist 40 RESPONSE AND REMISSION S TA R * D “ S w i t c h ” a n d “ A u g m e n t ” A l g o r i t h m s SWITCH Initiate Citalopram (maximum dose) (20mg) If intolerant or inadequate response switch to… Buproprion SR Sertraline Venlafaxine ER (400mg) (200mg) (375mg) AUGMENT Initiate Citalopram (maximum dose) (20mg) If inadequate response add… Best choice Second best choice Buproprion SR Buspiron (400mg) (60mg) 41 BIPOLAR DISORDER (1 of 4) • Prevalence is low but increasing in older adults • Bipolar disorders do not ‘burn out’ in old age • Few patients recover full function despite symptom remission • Mania causes hospitalization more and depression accounts for more disability • DSM-IVTR criteria for bipolar disorder type I (mania with or without depression) and type II (major depressive disorder without mania but with hypomania) are unchanged with age 42 BIPOLAR DISORDER (2 of 4) • Manic episodes often present with confusion, disorientation, distractibility, and irritability rather than with elevated, positive mood • Inflated self-esteem, grandiosity, and contentious claims of certainty also seen • Presence of psychosis, sleep disturbance, and aggressiveness may lead to mistaken diagnosis of dementia or depressive disorder 43 Mania • A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessary) (4 days for hypomania) • B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree – – – – – – 1. Inflated self-esteem or grandiosity 2. Decreased need for sleep (e.g. feels rested after only three hours of sleep) 3. More talkative than usual or pressure to keep talking 4. Flight of ideas or subjective experience that thoughts are racing 5. Distractibility 6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation – 7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments) BIPOLAR DISORDER (3 of 4) 45 • Late-onset mania is more often associated with medical disorders (stroke, dementia, or hyperthyroidism) or medications (antidepressants, steroids, stimulants) • Treatable components that contribute acutely to the person’s disability should be pursued • Careful inquiry of the family may reveal repeated hypomanic episodes that did not cause serious impairment but are clear indications of earlier disease BIPOLAR DISORDER (4 of 4) 46 • Bipolar disorder type II is characterized by recurrent major depressive episodes interspersed with periods of hypomania • Past episodes of hypomania may be unrecognized by patient and family • Mixed states occur in which criteria for both mania and major depressive disorder are present T R E AT M E N T O F BIPOLAR DISORDER • Most primary providers refer suspected cases to a psychiatrist due to the frequency of recurrence, psychosis, and suicidality • Family-focused treatment prevents recurrent episodes of illness and delays hospitalization when accompanied by pharmacotherapy • Pharmacotherapy prevents recurrent episodes but is less effective without family- focused treatment 47 48 PHARMACOTHERAPY FOR MANIA AND BIPOLAR D E P R E S S I O N : L I T H I U M C A R B O N AT E • Target plasma levels for older patients: 0.6–1.0 mEq/L • Use cautiously with renal insufficiency (once-daily dosing) • Up to 1–2 wks to achieve steady state • May increase lithium levels: NSAIDs, thiazide- and K+-sparing diuretics, furosemide Dehydration, salt depletion • Side effects: fine resting tremor, myoclonus, intention tremor 49 PHARMACOTHERAPY FOR MANIA AND BIPOLAR D E P R E S S I O N : VA L P R O I C A C I D • Target concentrations of 50–100 g/mL • Efficacy comparable to lithium; FDA-approved for bipolar disorder • Up to 1–2 wks to achieve steady state • Side effects: Sedation, rashes, platelet counts & functioning Liver toxicity may develop in patients with hepatic disease Reduce dosage in renal insufficiency Lab monitoring of CBC, liver enzymes, and chemistries required 50 PHARMACOTHERAPY FOR MANIA AND BIPOLAR DEPRESSION: ANTIEPILEPTIC AGENTS Carbamazepine • FDA-approved for bipolar disorder • Side effects: Mild bone marrow suppression with leukopenia & thrombocytopenia in 5%–10% of patients within first 2 wks Rarely: life-threatening agranulocytosis & aplastic anemia Lab monitoring required Lamotrigine • FDA-approved for bipolar depression • Little data on use in late life • Associated with Stevens-Johnson syndrome • Reduce dose in liver dysfunction 51 PHARMACOTHERAPY FOR MANIA AND BIPOLAR DEPRESSION: ANTIPSYCHOTIC AGENTS • Risperidone (0.25–6 mg; risk of movement disorder) FDA-approved for acute mania and mixed bipolar I episodes • Olanzapine (2.5–15 mg; may cause weight gain) FDA-approved for acute mania and mixed bipolar I episodes • Quetiapine (25–750 mg; may cause sedation) FDA-approved for acute mania and bipolar I and II depression • Aripiprazole (5–15 mg; little used in older adults) FDA-approved for acute mania and mixed bipolar I episodes Case Presentation • Clinical Course – Workup ordered, full labs including thyroid, within limits, CT checked without acute findings – Referral to see Geropsych the following day in the community – 2 weeks later had heard that she was on lexapro at the time – 2 months later family reported that she was also on lithium as adjunct therapy and now venlafaxine – 6 months later, follow up was that she remained on the lithium and venlafaxine, back to normal now. Independent and driving, no delusions, MMSE 30/30 Case Presentation • Lithium mainly for bipolar disorder • Adjunctive medication in patients with inadequate response for treatment of depression – Sometimes used as acute therapy • Network meta-analysis of 48 randomized trials (N>6000 depressed patients), of efficacy of 11 augmentation agents – Response more oftent with lithium than placebo (OR 1.56, 95% credible interval 1.05 – 2.55) • Watch out in renal impairment, low sodium, dehydration, CAD. – Monitor lithium levels, kidney, TFTs 54 S U M M A RY ( 1 o f 3 ) • In older adults, depression is: Common (especially “minor” depression) Associated with morbidity Difficult to diagnose because of atypical presentation, more somatic concerns, overlap with symptoms of other illnesses • Differential diagnosis: medical illnesses, dementia, bereavement • Suicide is a serious concern in depressed older patients, particularly older white males 55 S U M M A RY ( 2 o f 3 ) • Treatment (acute & preventive) should be individualized and may include: Psychotherapy Pharmacotherapy ECT • Choice of antidepressant should be based on comorbidities, side-effect profiles, patient sensitivity, potential drug interactions • Bipolar disorder is common in older psychiatric patients and may be treated with lithium, or antiepileptic or antipsychotic agents 56 S U M M A RY ( 3 o f 3 ) • Family-focused treatment improves the results of pharmacotherapy • Patients who do not respond to usual treatment for depression or mania should be referred to a geriatric psychiatrist 57 CASE 1 (1 of 4) • An 87-year-old white man comes to the office because he has had difficulty sleeping since the recent death of his best friend, who was with him in the army during World War II. He states that bad memories about the war keep him awake at night. • History includes chronic left leg pain (consequence of war injury), hypertension, hypercholesterolemia, and coronary artery bypass graft. • Medications include aspirin, simvastatin, and hydrochlorothiazide, and acetaminophen as needed. • His wife died 10 years ago; he lives alone and is independent in ADLs. He attends a senior center daily for lunch, but he is considering taking a break because the people there “get on his nerves.” 58 CASE 1 (2 of 4) • The patient has a good relationship with his children and grandchildren and is well groomed and pleasant during the visit. • On further questioning, he admits to more frequent concerns about his health. He denies thoughts of suicide but at times thinks that he would be better off dead. He does not have a firearm in his home. • On examination, he has lost 2.3 kg (5 lb) since his last visit 3 months ago. Cognition is intact. 59 CASE 1 (3 of 4) Which of the following is the most appropriate treatment recommendation? A. No treatment is necessary because his symptoms are minimal. B. He requires hospitalization because he is expressing suicidal thoughts. C. His symptoms of irritability and poor sleep indicate the need for treatment of bipolar disorder. D. His comorbidities preclude treatment with antidepressants. E. Treatment with an SSRI should begin immediately. 60 CASE 1 (4 of 4) Which of the following is the most appropriate treatment recommendation? A. No treatment is necessary because his symptoms are minimal. B. He requires hospitalization because he is expressing suicidal thoughts. C. His symptoms of irritability and poor sleep indicate the need for treatment of bipolar disorder. D. His comorbidities preclude treatment with antidepressants. E. Treatment with an SSRI should begin immediately. 61 CASE 2 (1 of 3) The 9-item Patient Health Questionnaire (PHQ-9) and the Geriatric Depression Scale (GDS) are the screening tests for geriatric depression with the best validity to support their use in primary care practice. 62 CASE 2 (2 of 3) Which of the following statements is true? A. Both the GDS and the PHQ-9 are self-administered. B. Both the GDS and the PHQ-9 screen for suicidal thoughts. C. The PHQ-9 can be used to assess treatment efficacy. D. The GDS is more influenced by medical comorbidity than the PHQ-9. E. The GDS and PHQ-9 each requires >30 minutes to administer. 63 CASE 2 (3 of 3) Which of the following statements is true? A. Both the GDS and the PHQ-9 are self-administered. B. Both the GDS and the PHQ-9 screen for suicidal thoughts. C. The PHQ-9 can be used to assess treatment efficacy. D. The GDS is more influenced by medical comorbidity than the PHQ-9. E. The GDS and PHQ-9 each requires >30 minutes to administer. 64 CASE 3 (1 of 4) • An 80-year-old woman comes to the office to request a prescription for an antidepressant. Over the past 2 months she has been sleeping poorly, and her appetite has decreased. She describes feeling miserable all the time, crying often, and fighting with everybody. She has no somatic symptoms. • History includes obesity, hypothyroidism, osteoarthritis, and longstanding bipolar disorder. Medications include levothyroxine and acetaminophen as needed. • She has been asymptomatic off medication for bipolar disorder for 2 years; shortly before she stopped, she experienced lithium toxicity and was hospitalized. 65 CASE 3 (2 of 4) • The patient and her family believe that the bipolar disorder has abated because of her age. • Physical examination is unremarkable. She appears restless, starts to talk of a new hobby, but then switches topic. • There is a substantial change from her baseline cognition: she is not sure of the date, and she makes mistakes about events that are familiar to her. • CBC and basic chemistry panel are within normal limits. • Over the next 24 hours, she becomes increasingly tearful, confused, and restless. 66 CASE 3 (3 of 4) Which of the following is most likely to be true? A. B. C. D. E. Before offering a psychotropic medication, additional tests are needed to exclude a medical illness that may be causing delirium. Treatment with an antidepressant is likely to improve her symptoms. The presentation suggests development of dementia with behavioral problems that is unlikely to respond to medications. A mood stabilizer will slowly improve her confusion resulting from bipolar disorder. A sedative will improve her anxiety and associated lack of sleep. 67 CASE 3 (4 of 4) Which of the following is most likely to be true? A. B. C. D. E. Before offering a psychotropic medication, additional tests are needed to exclude a medical illness that may be causing delirium. Treatment with an antidepressant is likely to improve her symptoms. The presentation suggests development of dementia with behavioral problems that is unlikely to respond to medications. A mood stabilizer will slowly improve her confusion resulting from bipolar disorder. A sedative will improve her anxiety and associated lack of sleep. 68 GRS8 Slides Editor: Annette Medina-Walpole, MD, AGSF GRS8 Chapter Author: Gary Kennedy, MD GRS8 Question Writer: Alessandra Scalmati, MD Medical Writers: Beverly A. Caley Faith Reidenbach Managing Editor: Andrea N. Sherman, MS Copyright © 2013 American Geriatrics Society