September 26 28, 2013 Westin Tampa Harbour Island. Co-sponsored by

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1 September 26 28, 2013 Westin Tampa Harbour Island Co-sponsored by

2 Best Practices in the Management of Geriatric Depression Sarah Hollingsworth Lisanby, MD Duke University School of Medicine Durham, NC Alan F. Schatzberg, MD Stanford University School of Medicine Stanford, CA

3 Sarah Hollingsworth Lisanby, MD Disclosures Grants: Brainsway Ltd.; NeoSync Inc. Equipment Support: Magstim; MagVenture, Inc.

4 Alan F. Schatzberg, MD Disclosures Research/Grants: Sunovion Pharmaceuticals Inc. Speakers Bureau: Merck & Co., Inc. Consultant: Bay City Capital LLC; CeNeRx BioPharma; Cervel Neurotech, Inc.; Eli Lilly and Company; Genentech, Inc.; Gilead; Lundbeck/Takeda Pharmaceuticals U.S.A., Inc.; McKinsey & Company; Merck & Co., Inc ; MSI Pharma; Neuronetics Inc.; PharmaNeuroBoost; Xhale, Inc. Equity: Amnestix, Inc.; BrainCells Inc.; Cervel Neurotech, Inc.; Corcept Therapeutics; Delpor, Inc.; Forest Laboratories, Inc.; Merck & Co., Inc.; Neurocrine Biosciences, Inc.; Pfizer Inc.; Xhale, Inc. Intellectual Property: Named inventor on pharmacogenetic and antiglucocorticoid use patents on prediction of antidepressant response.

5 Learning Objective 1 Use validated assessment tools to detect and measure the severity of geriatric depression

6 Learning Objective 2 Implement treatment for geriatric depression based on evidence-based best practice

7 Geriatric Depression Common Treatable Underdiagnosed and undertreated Significant disease burden! Morbidity! Mortality

8 Prevalence of Elderly Depression in Different Care Settings Care setting Prevalence of depressive symptoms Prevalence of major depressive disorder Community 15% 1% - 3% Primary care 20% 10% - 12% Acute hospital 20% - 25% 10% - 15% Long-term care 30% - 40% 16% Barua A, et al. Annals of Saudi Medicine. 2011;31(6): PMID:

9 Why Treat Geriatric Depression? Increased disability Substantially increases the likelihood of death from physical illnesses Increased impairment from a medical disorder When untreated, interferes with a patient's ability to follow a necessary treatment regimen Increased use of health care resources Increased healthcare costs! Healthcare costs of elderly people! 50% higher than those of nondepressed seniors Lasts longer in older persons Ellison JM, et al. Psychiatric Clin N Am. 2012;35(1): PMID:

10 Geriatric Depression: Bio, Psycho, Social Determinants BIOLOGICAL! Genetic! High prevalence in first-degree relatives! High concordance in monozygotic twins! Medical illness! Vascular changes in the brain! Chronic or severe pain! Previous history of depression PSYCHOLOGICAL! Traumatic experiences! Damage to body image! Fear of death! Frustration with memory loss! Role transitions SOCIAL! Loneliness, isolation! Recent bereavement! Lack of a supportive social network! Decreased mobility! Due to illness or loss of driving privileges Ellison JM, et al. Psychiatric Clin N Am. 2012;35(1): PMID:

11 Major Depression in Neurologic Disorders Associated with Aging Stroke 40% -60% Parkinson disease 30-40% Alzheimer s disease 20% - 40% Valkanova V, et al. Biol Psychiatry. 2013;73(5): PMID:

12 Medications That May Cause Depressive Symptoms Anabolic steroids Anti-arrhythmic medications Anticonvulsant medications Barbiturates Benzodiazepines Carbidopa or levodopa Certain beta-adrenergic antagonists Clonidine Cytokines (specifically IL-2) Digitalis preparations Glucocorticoids (prednisone) H2 blockers Metoclopramide Opioids

13 Factors That Complicate the Diagnosis of Geriatric Depression Presentation! Low/depressed mood need not be present! Persistent loss of pleasure and interest in previously enjoyable activities (anhedonia) must be present! Masked depression or depression without sadness mainly somatic complaints! Often co-occurs with other serious illnesses Patient factors! Think depressive symptoms are a normal part of aging! Reject diagnosis of depression

14 Clinical Presentation of Geriatric Depression Compared with young persons who are depressed, older persons with depression have:! Less disturbed sleep (19% vs. 25%)! Less appetite disturbance (16% vs. 27%)! Less disturbed energy (11% vs. 18%)! Less guilt (5% vs. 13%)! Less diminished concentration (8% vs. 16%)! Fewer thoughts about death (22% vs. 31%) Weissman M, et al. Affective Disorders. In Psychiatric Disorders in America 1991.

15 Geriatric Depression: Assessment Tools Geriatric Depression Scale (GDS)! Validated, 15-item scale! Scoring: > 5 points or positive responses is diagnostic Cornell Scale for Depression in Dementia! Scoring: > 12 means probable depression Center for Epidemiologic Studies of Depression Scale (CES-D) Patient Health Questionnaire 9 (PHQ-9)! 9-item scale! Self-rated Dennis M, et al. Age Ageing. 2012;41(2): PMID:

16 Geriatric Depression Scale (GDS) Validated, standardized scale available locally for screening of depression Cut-off point of 8/15 Can be used by trained nonmedical personnel Yesavage J, et al. J Psychiatr Res. 1982;17(1): PMID:

17 Geriatric Depression Scale (GDS): Short Form Questions Choose the best answer for how you have felt over the past week: 1. Are you basically satisfied with your life? 2. Have you dropped many of your activities and interests? 3. Do you feel that your life is empty? 4. Do you often get bored? 5. Are you in good spirits most of the time? 6. Are you afraid that something bad is going to happen to you? 7. Do you feel happy most of the time? 8. Do you often feel helpless? Yesavage J, et al. J Psychiatr Res. 1982;17(1): PMID:

18 Geriatric Depression Scale (GDS): Short Form Questions 9. Do you prefer to stay at home, rather than going out and doing new things? 10. Do you feel you have more problems with memory than most? 11. Do you think it is wonderful to be alive now? 12. Do you feel pretty worthless the way you are now? 13. Do you feel full of energy? 14. Do you feel that your situation is hopeless? 15. Do you think that most people are better off than you are? Yesavage J, et al. J Psychiatr Res. 1982;17(1): PMID:

19 Differential Diagnosis Depression vs. Dementia DEPRESSION Subacute onset Family recognition early Rapid progression Impairment inconsistent over time Patient admits deficits DEMENTIA Insidious onset Delayed family recognition Slow progression Impairment consistent; slow, gradual decline Patient denies or is unaware of deficits Naismith SL, et al. Prog Neurobiol. 2012;98(1): PMID:

20 Differential Diagnosis Depression vs. Dementia (cont d) DEPRESSION Appears depressed Anhedonia Abstract thought usually normal I don t know response to questions Patient often unconcerned DEMENTIA Not depressed Can experience pleasure Abstract thought impaired Near-miss answers Patient tries to cover up Naismith SL, et al. Prog Neurobiol. 2012;98(1): PMID:

21 Antidepressants in Older Patients All antidepressants are equally efficacious SSRIs are better tolerated than TCAs Escitalopram, citalopram, sertraline, venlafaxine, and mirtazapine may have fewer drug interactions SSRI-related side effects seen in older persons! Extrapyramidal side effects! Apathy! Anorexia! SIADH! Upper GI bleeding SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; SIADH = syndrome of inappropriate antidiuretic hormone; GI = gastrointestinal. Boyce RD, et al. J Am Med Dir Assoc. 2012;13(4): PMID:

22 Using Antidepressants in Older Patients Start low and go slow SSRIs are used at the same dose as adults Response time is longer in elderly, > 6 12 weeks Because of higher risk of relapse in older persons, continue antidepressants for > 2 years after remission of major depressive disorder Boyce RD, et al. J Am Med Dir Assoc. 2012;13(4): PMID:

23 Nonmedical Interventions Balanced diet Fluids Exercise Avoid alcohol Family support/ social support Focus on positives Promote autonomy Promote creativity Alternative therapy (e.g., pet therapy) Pace appropriately Inform about depression Avoid stressors Ellison JM, et al. Psychiatric Clin N Am. 2012;35(1): PMID:

24 What Do We Know About Elderly Suicide? Higher rate, higher lethality, greater determination, and fewer warning signs 1 Risk factors: past history of suicide, physical illness, psychiatric illness, and certain personality traits 1 Majority make contact with a primary care physician one month before their suicide (but not necessarily for a mood problem), and most remain undetected 2 Paradoxically, risk increases as patient begins to respond to treatment 2 1 Conwell Y, et al, Biol Psychiatry. 2002;52(3): PMID: Chiu HF, et al. Acta Psychiatr Scand. 2004;109(4): PMID:

25 National Suicide Statistics at a Glance Centers for Disease Control and Prevention [CDC] National Center for Health Statistics; National Institute of Mental Health. CDC Website. suicide/statistics/trends02.html. 2013

26 What Is the Most Effective and Rapidly Acting Treatment for a Suicidal, Depressed Older Person?

ECT for Depression ECT vs. sham! N = 256! Effect size 0.

2007;357(19):1939-1945. PMID: 17989386.; UK ECT Review Group.

27 ECT for Depression ECT vs. sham! N = 256! Effect size 0.91 ECT vs. medication! N = 1,144! Effect size 0.80 Consortium for Research on ECT (CORE)! N = 217! Response rate 75% Lisanby SH. N Engl J Med. 2007;357(19): PMID: ; UK ECT Review Group. Lancet. 2003;361(9360): PMID: ; Husain MM, et al. J Clin Psychiatry. 2004;65(4): PMID:

28 Relief of Suicidal Intent by ECT: Relief Is Rapid Number of Subjects Whose Suicide Score Resolved to Zero N = 106/131 (81%) HRDS Suicide 3, Score 4 of 3, 4 Baseline HRSD24 Suicide Item (Item #3) Score HRSD 24 = Hamilton Depression Rating Scale, 24-item. Kellner PT, et al. Am J Psychiatry. 2005;162: PMID:

29 Relief of Suicidal Intent by ECT: Number of ECT Needed 100% Percentage of patients reporting suicidal thoughts Percentage of Patients 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Number of Treatments % patients reaching 0 Cumulative percent reaching 0 Number of ECT Needed to Resolve Suicide Risk Among All Patients with Baseline Self-Rating 2 Kellner PT, et al. Am J Psychiatry. 2005;162: PMID:

30 Limitations of ECT Cognitive side effects! New brain stimulation interventions offer safer alternatives Post-ECT relapse! Novel maintenance strategies offer sustained benefit Lisanby SH. N Engl J Med. 2007;357(19): PMID:

31 New Treatments on the Horizon Transcranial magnetic stimulation (TMS) Transcranial direct current stimulation (tdcs)

32 Prolonging Remission in Depressed Elderly (PRIDE)

33 Sponsor & DSMB Clinical Coordinating Centers Multiple-PI: Kellner Multiple-PI: Lisanby Data Coordinating Center PI: Knapp Clinical Centers PI: Young PI: Lisanby PI: Kellner Hoboken: Greenberg PI: Sampson PI: Petrides PI: Husain PI: McCall

34 PRIDE Study Prolonging Remission in Depressed Elderly Aims! To compare the efficacy of PHARM (Li+VLF) versus STABLE (flexible, continuation ECT plus Li+VLF) in maintaining remission in latelife depression! To compare the functional outcomes and tolerability, PHARM versus STABLE Li = lithium; VLF=venlafaxine. Borroughs H, et al. Fam Pract. 2006;23(3): PMID:

Frontal TMS Frontal Sham Parietal TMS Parietal Sham Block 1 Block 2 Block 3 Block 4 Block 5 Block 6 1 Hz Retention 5 Hz

35 Facilitation of Performance in a Working Memory Task With Rtms Stimulation of the Precuneus N = 44 Dose-finding study, within-subject cross-over 5 Hz TMS to precuneus during retention phase reduced RT by 50 ms Day 1 Day 2 Day 3 Day 4 Frontal TMS Frontal Sham Parietal TMS Parietal Sham Block 1 Block 2 Block 3 Block 4 Block 5 Block 6 1 Hz Retention 5 Hz Retention 20 Hz Retention 1 Hz Probe 5 Hz Probe 20 Hz Probe Luber B, et al. Brain Res. 2007;12;1128(1): PMID:

Remediation of Sleep-Deprivation-Induced Working Memory

(TMS) Within-subject cross-over 5 Hz TMS to superior occipital

state, not seen in sleep replete Degree of improvement correlated

Deprivation TMS Tues 8 AM Thurs 12 PM r = - 0.58, p < 0.

36 Remediation of Sleep-Deprivation-Induced Working Memory Impairment With fmri-guided Transcranial Magnetic Stimulation (TMS) Within-subject cross-over 5 Hz TMS to superior occipital gyrus reduced RT by 143 ms Effect specific to sleep-deprived state, not seen in sleep replete Degree of improvement correlated with network expression Set size 6 Cerebral Cortex Sleep Deprivation TMS Tues 8 AM Thurs 12 PM r = , p < Sleep-deprived 60 hrs, N = 15. Luber B, et al. Cereb Cortex. 2008;18(9): PMID:

painless Enhances verbal fluency, word recall, recovery of function

37 Transcranial Direct Current Stimulation Direct current (1 ma) polarizes cortex Anodal facilitates, cathodal inhibits Effects last hrs Safe, painless Enhances verbal fluency, word recall, recovery of function post-stroke Cheap, portable Columbia Brain Stimulation & Therapeutic Modulation Division.

38 Questions & Answers

39 Co-sponsored by

SUTTER PHYSICIANS ALLIANCE (SPA) 2800 L Street, 7 th Floor Sacramento, CA 95816

SUTTER PHYSICIANS ALLIANCE (SPA) 2800 L Street, 7 th Floor Sacramento, CA 95816 SPA PCP Treatment & Referral Guideline Managing Depression in Older Adults Developed March 1, 2003 Revised September 21,