The Association between Late-life The Association between Late-life Depression and Medical IllnessDepression and Medical Illness

Maria D. Llorente MD

Professor Dept. of Psychiatry & Behavioral Sciences

Miller School of Medicine at the University of Miami

The “Graying” of The “Graying” of AmericaAmerica

By the year 2025, the world’s older population (60 and older) will approach 1.2 billion.

By the year 2030, 1 of every 5 people in the U.S. will be 65 or older.

Older Americans will number more than 65 million

U.S. Dept of Health and Human Services. Mental Health: A Report of the Surgeon General. Rockville, MD: U.S. Dept of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Mental Health Services, NIH, NIMH, 1999.

Late-Life DepressionLate-Life Depression

• Incidence of major depression declines with age, but minor depression is much more common

• Depressive symptoms occur in 15%–25% of older adults (>65 years) that fail to meet criteria but cause distress and interfere with functioning

• Fewer than half of depressed seniors are recognized as being depressed and of those who are identified fewer than half receive treatment

Primary Care is the De Facto Primary Care is the De Facto Mental Health System (in the Mental Health System (in the

United States) responsible for the United States) responsible for the care of more patients with mental care of more patients with mental

disorders than the specialty disorders than the specialty mental health sector.mental health sector.

Regier et al. Arch Gen Psychiatry 1993; 50:85-94

Depression Guideline Panel. Depression in Primary Care: Vol 1. Detection and Diagnosis. Clinical Practice Guideline No. 5. Rockville, MD: US Dept of Health and Human Services. Public Health Service, Agency for Health Care Policy and Research; no. 93-0550; 1993. Kessler RC et al. J Affect Disord. 1993;29:85-96. Kessler et al., JAMA 2003; Evans et al., J Clin Psych 1999; Astrom et al., Stroke, 1993; Tiller et al., Psychopharm 1992; Meaf et al., Neurology 1994; Cumming Am J Psych 1992.

• 16.2% of US population report at least one lifetime episode

• More than half of patients have first episode by age 40

• 25% of older cancer patients

• 25-50% of post-stroke patients

• 1/3 of Alzheimer’s patients

• 50% of Parkinson’s patients

• 30% of post-MI Patients

Epidemiology of Major Epidemiology of Major DepressionDepression

Minority ElderlyMinority Elderlyand Depressionand Depression

HISPANIC

• >65 will increase by more than 450% by 2050

• Depressive disorder prevalence in primary care increased from 4.5% to 8.6% between 1992-97

• Higher prevalence of depressive symptoms (11-40%)

• Higher depression-associated mortality from both suicide and medical disorders

AFRICAN-AMERICAN

• >65 will increase by 131% by 2030

• Lower rates of depression recognition and treatment

• Poorer medical outcomes associated with comorbid depression (EX: diabetes and stroke/hyperglycemia/renal failure/hypertriglyceridemia)

0

5

10

15

20

25

30

Community Primary CareClinic

MedicalInpatientSetting

NursingHome

Prevalenceof Major

Depression (%)

Katon W, Schulberg H. Gen Hosp Psychiatry. 1992;14:237-247.Rosen J, Mulsant BH, Pollock BG. Nursing Home Med. 1997;5:156-165.

2%–4%

5%–10%

6%–25%

6%–14%

Major Depression Is Major Depression Is Associated with Chronic Associated with Chronic

Medical IllnessMedical Illness

Preskorn SH. Outpatient Management of Depression: A Guide for the Primary Care Practitioner. 2nd ed. Caddo, OK: Professional Communications, Inc.; 1999: Chapter 2.

Impact of Untreated Depression: Impact of Untreated Depression: Morbidity & MortalityMorbidity & Mortality

• Patient morbidity

– Poorer health outcomes

– Suicide attempts

– Accidents

– Lost jobs

– Alcohol Use & Abuse

– Marital Problems

• Mortality

– Older white men have highest suicide rates

– Fatal accidents

– Death due to related medical complications

• Societal costs

– Caregiver burden

– Higher medical costs

– Increased healthcare utilization

DepressiveDisorder

Hypertension Diabetes Arthritis No ChronicCondition

Physical Function

Social Function

* P <0.05 vs depressive disorder.† Score of 100 = perfect functioning.Wells KB et al. JAMA. 1989;262:914-919.

Social orPhysical

FunctioningScore†

*

*

*

*

*

*

*

*

Comparison of Physical and Social Comparison of Physical and Social Functioning in Other Medical Functioning in Other Medical

IllnessesIllnessesDepression impairs physical and social functioning significantly more than these

medical illnesses

0

70

75

80

85

90

95

100

Medical Outcomes and Medical Outcomes and DepressionDepression

Major Depression: Major Depression: Post-MI SurvivalPost-MI Survival

05

10152025

06 12 18

months

% Cardiac Mortality

Frasure-Smith, Lesperance, 1998

Depressed (N=35)

Non-depressed (N=187)

OR = 3.6

Major Depression and Major Depression and Congestive Heart FailureCongestive Heart Failure

• More severe medical illness and more functional impairment than non-depressed (Freedman 2001)

• Utilize more inpatient/outpatient medical services than non-depressed (Koenig, 1998)

Major Depression and Major Depression and Congestive Heart FailureCongestive Heart Failure

• Associated with increased risk of functional decline or death at 6 month f/u (Vaccarino, 2001)

• Depression is significant predictor of mortality in clinically stable CHF patients (Murberg, 1999)

• Greater severity of depression associated with 3-fold increased risk of mortality at 1 year f/u than non-depressed (Jiang, 2001)

Major Depression and Major Depression and Diabetes MellitusDiabetes Mellitus

• 28% of sample reported moderately severe symptoms of depression and/or anxiety

• Significant association between depressive symptoms and high Hgb A1C in men

• 1/3 reported they’d like counseling

Lloyd et.al. Diabet Med 2000 Mar;17(3):198-202

Major Depression and Major Depression and Diabetes MellitusDiabetes Mellitus

• Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glucose control.

• A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis.

• Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001).

Lustman et.al. Diabetes Care 2000 Jul;23(7):934-42

Major Depression and Major Depression and Diabetes MellitusDiabetes Mellitus

• 183 African-American men with diabetes

• 30% had significant depressive symptoms (CES-D >22)

• Greater depressive symptoms significantly associated with higher serum levels of cholesterol and triglycerides (P<0.050).

Gary et.al. Diabetes Care 2000 Jan;23(1):23-9

Medical Illness, Depression and Medical Illness, Depression and SuicideSuicide

• Record-linkage of 2323 suicides among 1.9 million people 50 and older in Denmark showed that neoplasms, circulatory/respiratory and digestive diseases confer increased risk; infections, nutritional, metabolic diseases increased risk for hospitalized men; did not control for mood disorders (Erlangsen et al; JAGS 2005)

• Pulmonary disease, cancer, visual impairment and neurological disorder confer risk after adjusting for mood disorders (Waern et al; BMJ 2002)

Suicide Rates By Age & Gender Suicide Rates By Age & Gender (Per 100,000)(Per 100,000)

0

20

40

60

80

85+WHITE M WHITE F AA M AA F

0

10

20

30

40

50

60

70CDC. National Center for Health Statistics; 2000

Suicide and Suicide and Lifetime Axis I Diagnosis By Lifetime Axis I Diagnosis By

AgeAge

0

20

40

60

80

100

21-54 55-74 75

Affective syndromesOther (primary psychosis, ETOH, substance, etc)No diagnosis

Conwell, Am J Psychiatry, 1994

Reasons for Underdiagnosis of Reasons for Underdiagnosis of Late-life Depression in Primary Late-life Depression in Primary

CareCare

• Over-identification with the patient

• Lack of time

• Lack of training in mental health

• False belief that older adults won’t respond to treatment

• Atypical symptoms in older adults

* Must include 1 of theseDSM-IV-TR. Washington, DC: American Psychiatric Association. 2000.

Sleep: Insomnia or hypersomnia

Interest*:Depressed mood* Loss of interest*

Guilt: Feelings of worthlessness

Energy: Fatigue

Concentration: Diminished ability to think or

make decisions

Appetite: Weight change

Psychomotor: Psychomotor slowing or agitation

Suicide: Preoccupation with death

5 Symptoms in the same 2-week period

DSM-IV-TR Criteria for DSM-IV-TR Criteria for Major DepressionMajor Depression

Clinical Features of Late-life Clinical Features of Late-life DepressionDepression

• “Depression” without sadness

• Irritability

• Prominent Anxiety

• Cognitive complaints

• Prominent vague somatic complaints

• Unexplained health worries

• Heightened pain complaints

• Loss of interest and pleasure

• Social withdrawal or avoidance of social interactions

• Multiple primary care visits without resolution of the problem

• Unexplained functional decline

Early-onset v. Late-onsetEarly-onset v. Late-onset Early-onset• Index episode in childhood

or early adult life

• First degree relatives with depression

• Less physical illness

• More psychiatric comorbidity (SUD; personality disorders)

• Sad mood

Late-onset• Index episode after age 50

• Less genetic predisposition

• Chronic physical illness

• Poorer treatment response with more chronic course

• Increased mortality

• Abnormal brain imaging

• Les psych comorbidity

• Apathy and anhedonia

Euthymia

Symptoms

Syndrome

Treatment phases

Prog

ression

to disorder

Acute(6–12 wk)

Continuation(4–9 mo)

Maintenance( 1 yr)

TimeTime

Incr

ea

sed

Incr

ea

sed

sev

eri

tys

eve

rity

RelapseRelapse

ResponseResponse

RemissionRemission

RecurrenceRecurrenceRelapseRelapse

Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28.

+

+

Phases of Treatment for DepressionPhases of Treatment for Depression

APA Practice Guidelines for the Treatment of Psychiatric Disorders. 2000.

Treatment GoalTreatment Goal

The goal of treatment with either antidepressant medication or

psychotherapy in the acute phase is the remission of

major depressive disorder symptoms

PseudodementiaPseudodementia

• Patients may present with complaints of loss of memory

• Frequent “I don’t know responses” on exam

• Often a prodrome of dementing illness (as many as 50% may develop dementia within 5 years)

• If prodromal, usually late-onset, with prominent psychomotor retardation and/or psychotic features

• Consider frequent neurocognitive testing, and early use of cognitive-enhancing agents.

Vascular depressionVascular depression

• Frontostriatal disconnection/dysfunction (Executive dysfunction – impairment in IADLs)

• Prominent psychomotor slowing and apathy

• Poorer response to treatment, higher risk of relapse and recurrence

• Limited vegetative symptoms and little depressive ideation

• Brain imaging abnormalities: enlarged ventricles, white matter hyperintensities

Post-stroke depressionPost-stroke depression

• 3-6 months after CVA

• Prominent vegetative features

• Larger lesion volumes

• Likely biological pathogenesis

• 12-24 months after CVA

• Fewer vegetative symptoms, more apathy

• Associated with significant social and physical impairments

Depression with PsychosisDepression with Psychosis

• 4% of depressed elderly

• 45% of psychiatrically hospitalized elderly

• Frequent and severe anxiety and agitation

• Somatic delusions common, but few hallucinations

• Nihilistic beliefs, hopelessness

• Often have suicidal ideations

• ECT indicated as first-line treatment

Minor Depression Minor Depression

• Subsyndromal Depression

• Associated with significant functional impairment and disability, lower quality of life and increased medical care utilization

• Associated with progression to depression at one year follow-up

• DSM-IV-TR: qualitatively similar to major depression, but only 2-4 symptoms needed

Caregiver Depression Caregiver Depression

• Often seen in those caring for older adult with dementia

• Associated with changing roles, increased responsibility, risk of social isolation, grief surrounding loss of demented person

• Often fail to recognize stress/burden, but report fatigue, insomnia, social withdrawal, and feeling “burned out”

• Affects quality of caregiving

Caregiver Depression Caregiver Depression

Barriers to open discussion:• Need to protect themselves from feelings of

disloyalty due to “complaining about” loved one

• May represent failure as caregiver

• Family already burdened with demented loved one, don’t want to add to burden

• Fear of own feelings of anger, guilt, ambivalence

• Need to approach from the perspective of enhancing the care provided

Family Intervention and Nursing Home Placement

0

0.2

0.4

0.6

0.8

1

1 2 3 4 5 6 7 8

Survival time (year)

Cu

mu

lati

ve

pro

po

rtio

n o

f s

urv

ivin

g p

ati

en

ts

Treatment ControlMittelman, JAMA 1996

Bereavement Bereavement • Losses frequently encountered in late-life that lead to

bereavement

• Features that distinguish depression from bereavement:

•Guilt

•Suicidal thoughts

•Morbid preoccupation wit h worthlessness

•Psychomotor retardation

•Prolonged and marked functional impairment

•Complex hallucinations (not just thinking they heard voice of loved one, or transiently saw their image

Comorbidity of Depression & Comorbidity of Depression & AnxietyAnxiety

• Nearly 3/4 of community-dwelling adults with lifetime Major Depression also meet criteria for at least 1 other DSM-IV diagnosis

• Most (59.2%) of these are anxiety disordersKessler et al., JAMA 2003

• 86% of older adults with anxiety disorders also met criteria for a depressive disorder

PRISM-E, (Bartels et al, Am J Psych 2005)

Comorbidity of Depression & Comorbidity of Depression & AnxietyAnxiety

• In older adults, comorbid anxiety disorder and depression is associated with:

- greater symptom severity

- poorer social functioning

- more difficult course of illness

- decreased or delayed treatment response

- higher level of suicidality

Angst 1999, Roy-Byrne 2000, Lenze 2000, 2001, Bartels 2002

Do Anxiety Symptoms Also Respond Do Anxiety Symptoms Also Respond to Antidepressant Medication to Antidepressant Medication

Treatment? Treatment?

• A randomized, double-blind, flexible-dose study

• 24 wk treatment

• Citalopram (Celexa) N = 52

• Paroxetine (Paxil) N = 52

• Dose range: 20–40 mg/d

• Outcome measures: HAMD-24, HAMA

• Outpatients age18–65 years

• DSM-IV major depression and mixed anxiety/depression

• HAMD-24 baseline score 18 for depressive symptoms

• HAMA baseline score 17 for anxiety symptoms

Study Design Inclusion Criteria

Jefferson J, Greist JH. Poster presented at APA, 2001.

Effects on Depression: Effects on Depression: Citalopram vs ParoxetineCitalopram vs Paroxetine

Jefferson J, Greist JH. Poster presented at APA, 2001.

-20

-16

-12

-8

-4

0

0 1 2 4 6 8 12 16 20 24

Citalopram Paroxetine

Treatment Week

HAMD-24Mean ChangeFrom Baseline

20–40 mg/d(n = 52)

20–40 mg/d(n = 52)

Effects on Anxiety: Effects on Anxiety: Citalopram vs ParoxetineCitalopram vs Paroxetine

Jefferson J, Greist JH. Poster presented at APA, 2001.

-16

-12

-8

-4

0

0 1 2 4 6 8 12 16 20 24

Citalopram Paroxetine

Treatment Week

HAMAMean ChangeFrom Baseline

20–40 mg/d(n = 52)

20–40 mg/d(n = 52)

Antidepressant DosesAntidepressant DosesMedication Initial

Dose (mg/d)

Usual Dose

Adult Geriatric

Concerns

Fluoxetine (Prozac) 10 20-40 10-20 P450 interactions

Sertraline (Zoloft) 25 100-250 75-150 P450 interactions

Paroxetine (Paxil) 10 20-60 20-40 Anticholinergic

Citalopram (Celexa) 10 20-60 20 Somnolence

Escitalopram (Lexapro) 10 10-20 10 Nausea/insomnia/activation

OTHERS

Bupropion (Wellbutrin) 75 100-300 150 Seizures

Nefazodone (Serzone) 50 200-400 100-150 Hepatitis

Trazodone (Desyrel) 25-50 100-400 75-150 Anticholinergic

Mirtazapine (Remeron) 15 15-45 15-45 Somnolence

Venlafaxine (Effexor) 25 150-225 75-150 BP

Keller MB, et al. Arch Gen Psychiatry. 1992;49:809-816.

Hypotheses for Low Remission Rates in Major Depression

• Patients satisfied with incomplete response

• Patients, clinicians do not expect remission

• Treatments may not be well tolerated

• Physicians not comfortable or familiar with recommended optimal dosages

Electro-convulsive therapyElectro-convulsive therapy

Indicated in patients who:

• Are acutely suicidal

• Have major depression with psychotic features

• Have failed 2 adequate trials of antidepressants

• Cannot tolerate antidepressant tx

• Have previously responded to ECT and prefer this tx

Patients on average need 6-8 treatments

General Principles of Late-life General Principles of Late-life Depression ManagementDepression Management

• Education for patient/family that meds are not effective until patient has taken them for the right amount of time (usually 3-6 weeks) in the right dose

• Start low, go slow, but go – need to reach therapeutic dose

• Minimum duration is 9-12 months after symptom remission for first episode

• Recommend long-term treatment in patients with 2 or more lifetime episodes

Evidence-based Management of Late-life Depression

• Annual screening for depression in all patients

• Patients who screen positive are assessed within 6 weeks for a depressive disorder and/or suicidal ideas

• Those who assess positive require treatment with either therapy/ medication alone or in combination

• At least 3 follow-up visits within first 3 months

• Index episode treated for at least 9-12 months

• Recurrent episode maintained on antidepressant long-term