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September 26 – 28, 2013 | Westin Tampa Harbour Island

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

Sarah Hollingsworth Lisanby, MD

● Grants: Brainsway Ltd.; NeoSync Inc. ● Equipment Support: Magstim; MagVenture, Inc.

Disclosures

Alan F. Schatzberg, MD

●  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.

Disclosures

Learning Objective

Use validated assessment tools to detect and measure the severity of geriatric depression

1

Learning Objective

Implement treatment for geriatric depression based on evidence-based best practice

2

Geriatric Depression

● Common ● Treatable ● Underdiagnosed

and undertreated ● Significant disease

burden !  Morbidity !  Mortality

Prevalence of Elderly Depression in Different Care Settings

Barua A, et al. Annals of Saudi Medicine. 2011;31(6):620-624. PMID: 22048509.

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%

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):203-229. PMID: 22370499.

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

Ellison JM, et al. Psychiatric Clin N Am. 2012;35(1):203-229. PMID: 22370499.

●  SOCIAL !  Loneliness, isolation !  Recent bereavement !  Lack of a supportive social

network !  Decreased mobility !  Due to illness or loss of driving

privileges

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):406-413. PMID: 23237315.

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

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

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.

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):148-154. PMID: 22236655.

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):37-49. PMID: 7183759.

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):37-49. PMID: 7183759.

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):37-49. PMID: 7183759.

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):99-143. PMID: 22609700.

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):99-143. PMID: 22609700.

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):326-331. PMID: 22019084.

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):326-331. PMID: 22019084.

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):203-229. PMID: 22370499.

What Do We Know About Elderly Suicide?

● Higher rate, higher lethality, greater determination, and fewer warning signs1

● Risk factors: past history of suicide, physical illness, psychiatric illness, and certain personality traits1

● Majority make contact with a primary care physician one month before their suicide (but not necessarily for a mood problem), and most remain undetected2

● Paradoxically, risk increases as patient begins to respond to treatment2

1 Conwell Y, et al, Biol Psychiatry. 2002;52(3):193-204. PMID: 12182926. 2 Chiu HF, et al. Acta Psychiatr Scand. 2004;109(4):299-305. PMID: 15008804.

Centers for Disease Control and Prevention [CDC] National Center for Health Statistics; National Institute of Mental Health. CDC Website. http://www.cdc.gov/violenceprevention/suicide/statistics/trends02.html. 2013

National Suicide Statistics at a Glance

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 0.91

●  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):1939-1945. PMID: 17989386.; UK ECT Review Group. Lancet. 2003;361(9360):799-808.PMID: 12642045.; Husain MM, et al. J Clin Psychiatry. 2004;65(4):485-491. PMID: 15119910.

Relief of Suicidal Intent by ECT: Relief Is Rapid

HRSD24 = Hamilton Depression Rating Scale, 24-item. Kellner PT, et al. Am J Psychiatry. 2005;162:977-998. PMID: 15863801.

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Relief of Suicidal Intent by ECT: Number of ECT Needed

Kellner PT, et al. Am J Psychiatry. 2005;162:977-998. PMID: 15863801.

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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):1939-1945. PMID: 17989386.

New Treatments on the Horizon

● Transcranial magnetic stimulation (TMS) ● Transcranial direct current stimulation

(tDCS)

Prolonging Remission in Depressed Elderly (PRIDE)

Sponsor & DSMB

Clinical Centers

PI: Kellner Hoboken: Greenberg

PI: Lisanby

PI: Young PI: Sampson

PI: Petrides

PI: Husain

PI: McCall

Data Coordinating

Center

PI: Knapp

Clinical Coordinating Centers Multiple-PI: Kellner Multiple-PI: Lisanby

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 late-life depression

! To compare the functional outcomes and tolerability, PHARM versus STABLE

Li = lithium; VLF=venlafaxine. Borroughs H, et al. Fam Pract. 2006;23(3):369-377. PMID: 16476699

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

Luber B, et al. Brain Res. 2007;12;1128(1):120-129. PMID: 17113573.

Day 1 Day 2 Day 3 Day 4

TMSFrontal

ShamFrontal

TMSParietal

ShamParietal

Block 1 Block 2 Block 3 Block 4 Block 5 Block 6

Retention1 Hz

Retention5 Hz

Retention20 Hz

Probe1 Hz

Probe5 Hz

Probe20 Hz

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

Sleep-deprived 60 hrs, N = 15. Luber B, et al. Cereb Cortex. 2008;18(9):2077-2085. PMID:18203694.

Set size 6

r = - 0.58, p < 0.025

Tues 8 AM

Sleep Deprivation

Thurs 12 PM

TMS

Cerebral Cortex

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.

Questions & Answers

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