Depression and Older Adults
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Depression and Older Adults. Mark Snowden, M.D., M.P.H. Associate Professor University of Washington Medical Director Geriatric Psychiatry Services Harborview Medical Center. OVERVIEW. Prevalence and heterogeneity Major Depression Treatment Minor Depression Treatment Bereavement

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Depression and Older Adults

Mark Snowden, M.D., M.P.H.

Associate Professor

University of Washington

Medical Director Geriatric Psychiatry Services

Harborview Medical Center


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OVERVIEW

  • Prevalence and heterogeneity

  • Major Depression Treatment

  • Minor Depression Treatment

  • Bereavement

  • Depression in Dementia

  • Response to Drug Failure


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1 YR PREVALENCE AFFECTIVE DISORDER

Age (yrs) Odds Ratio

15-24

25-34

35-44

45-54

1.67*

1.32

1.35

1.0

* p<.05

(Kessler,RC et al. Arch Gen Psych Jan. ‘94)


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COHORT DEPRESSION RATES

.14

Cumulative

Depression

Rate .07

1935-44

1945-54

1955-64

1925-34

1915-24

1905-14

0

14 24 34 44 54 64 74

Age (yrs)


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PREVALENCE OF DEPRESSION IN GERIATRIC POPULATIONS

SettingMaj. Depr.

Community

Med. Clinics

Nursing Homes

1 - 4%

5 - 10%

12 - 20%


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PREVALENCE OF DEPRESSION IN GERIATRIC POPULATIONS

SettingMaj. Depr.Depr. Sxs.

8 - 16%

17 - 35%

30 - 45%

Community

Med. Clinics

Nursing Homes

1 - 4%

5 - 10%

12 - 20%


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Differential Diagnosis

Maj. Depression (Partial Remission)

Dysthymia

Minor Depression

Adj. Disorder w/ depressed mood

Mood Disorder due to Medical Condition

Depression of Alzheimer’s Dementia

Bereavement


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DSM IV MAJOR DEPRESSION CRITERIA

1) Depressed Mood

and/or

2) Anhedonia


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DSM IV MAJOR DEPRESSION CRITERIA

3) Anorexia/wt loss

4) Insomnia or Hypersomnia

5) Psychomotor Agitation or Retardation

6) Fatigue

7) Feelings of Worthlessness/Guilt

8) Indecisiveness/Trouble Concentrating

9) Recurrent Thoughts of Death/Suicide


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Late Onset vs Early Onset Depression

N=246

Symptom Odds Ratio

Loss of Interest * 4.01

Motor Retardation 0.57

Guilt Feelings 1.16

Pessimism 1.87

Psychotic Sxs. 0.58

Gen. Anxiety 0.72

* P<.05

(Krishnan et al. Am J Psychiatry, 5/95)


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OVERVIEW

  • Prevalence and heterogeneity

  • Major Depression Treatment

  • Minor Depression

  • Bereavement

  • Depression in Dementia

  • Response to Drug Failure


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NEW GENERATION ANTIDEPRESSANTS

  • Selective Serotonin Re-uptake Inhibitors

    • Fluoxetine (Prozac)

    • Sertraline (Zoloft)

    • Paroxetine (Paxil)

    • Citalopram (Celexa)

    • Escitalopram (Lexapro)


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SSRIs

  • More Alike than Different

  • Half Life:

    Fluoxetine>>citalopram>sertraline=paroxetine

  • Anticholinergic:

    Paxil mild > fluoxetine, sertraline, citalopram

  • Drug Interactions:

    Fluoxetine > paroxetine > sertraline, citalopram


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NEW GENERATION ANTIDEPRESSANTS

  • Bupropion (Wellbutrin)

  • Venlafaxine (Effexor)

  • Duloxetine (Cymbalta)

  • Mirtazepine (Remeron)


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BUPROPION

  • Different, Unknown therapeutic mechanism

  • Stimulant-like structure

  • Seizure Risks/Contraindication


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VENLAFAXINE XR

  • Low Dose: Serotonergic> Noradrenergic

  • Higher Dose: More combination 5HT & NE

  • Fewer Drug-Drug Interactions than SSRIs

  • Hypertension Side Effect


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Duloxetine

  • Combined Serotonergic and Noradrenergic

  • Decreased Risk Hypertension

  • Some efficacy for neuropathic pain


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MIRTAZEPINE

  • Serotonergic and Noradrenergic mechanisms

  • Mild-moderate sedation

  • Associated with some weight gain


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TRICYCLIC ANTIDEPRESSANTS

  • Tertiary (amitriptyline, imipramine, doxepin)

  • Secondary(nortriptyline, desipramine)

  • Secondary have fewer side effects

    Anticholinergic: desipramine < nortriptyline

    Orthostatic Hypotension: nortriptyline < desipramine

    Sedation: nortriptyline > desipramine


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OTHER CONSIDERATIONS

  • Sedation

    • more with mirtazepine

  • Sexual Dysfunction

    • less with bupropion

  • Hypertension Risk

    • venlafaxine

  • Seizure History

    • bupropion contraindicated


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GERIATRIC DOSING

___Initial (mg)__

10

10

25

10

10

20

75

37.5

15

Est. therapeutic Dose

50-125

10-40

50-200

20-60

20-40

40-60

200-450

150-375

30-45

Nortriptyline

Fluoxetine

Sertraline

Paroxetine

Citalopram

Duloxetine

Bupropion

Venlafaxine

Mirtazepine


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Antidepressant Duration

  • Low Dose: 1-2 wks before change

  • Intermediate dosing: 2-4 wks

  • Maximum Dose: 4-6 wks


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Intervention Example:Depression Care Management (Clinic)

  • Identification of depressed persons with a screening instrument

  • Measurement-based care

    • Psychotherapy

    • Antidepressants

  • Depression care manager (DCM) (MSW,Ph D, RN)

    • Treatment monitoring

    • Follow-up

    • Coordinate care with PCP

  • Goals

    • Improve low rates of engagement

    • Enhanced adherence to depression treatment


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Intervention Example:Depression Care Management (Clinic)

Core Elements

  • Active identification of depression

  • Evidence- and measurement-based treatment and outcomes

  • A person trained to support and deliver the treatment (“depression care manager”, DCM)

  • A consulting psychiatrist.


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Improving Mood-Promoting Access to Collaborative Treatment (IMPACT)

Unutzer J et al. JAMA

2002;288:2836-2845

  • RCT: N=1801, 60 yrs and older

  • 18 primary care clinics/ 5 states

  • Intervention: Depression Care Manager (RN or Ph.D) w/ supervising psychiatrist

    • Education

    • Care management

    • Support of antidepressants from PCP

    • Problem Solving Treatment

  • Usual Care Control


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IMPACT OUTCOMES (IMPACT)12 Months

45

%

25

19

8


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  • Prevalence and heterogeneity (IMPACT)

  • Major Depression Treatment

  • Minor Depression Treatment

  • Bereavement

  • Depression in Dementia

  • Response to Drug Failure


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Minor Depression (IMPACT)Research Criteria for Further Study

  • 2-4 of 9 criteria sxs for Maj. Depression

  • Depressed Mood or Anhedonia

  • No hx major depression, Mania

  • Not Dysthymic


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Minor Depression and Dysthymia (IMPACT)

in Primary Care Elderly

  • N= 415 pts>/=60yr

  • 11 wk, multi-center trial

  • 3-4 sxs at least 4wks AND Ham-D >9

  • RCT paroxetine vs placebo+usual care vs PST

Williams JW et al. JAMA

284:1519-1526, 2000


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Minor Depression and Dysthymia (IMPACT) in Primary Care Elderly

  • Mean change HSCL-20(1-4 points)

    • Paroxetine 0.61 PST 0.52 placebo 0.40

  • Statistically significant for paroxetine, not PST

Williams JW et al. JAMA

284:1519-1526, 2000


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HSCL-D-20 Scores by Treatment Assignment (IMPACT)

Williams, J. W. et al. JAMA 2000;284:1519-1526.


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HSCL-D-20 Scores of Patients With (IMPACT)

Minor Depression

Williams, J. W. et al. JAMA 2000;284:1519-1526.


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Remission Rate (IMPACT)

Williams, J. W. et al. JAMA 2000;284:1519-1526

  • Minor Depression

    • Paroxetine 53% PST 44% Placebo 49%

  • Dysthymia

    • Paroxetine 46% PST 51% Placebo 40%

      No treatment statistically significant vs Placebo


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PROSPECT (IMPACT)Prevention of Suicide in Primary Care Elderly: Collaborative Trial

  • N=598 elderly, 20 primary care clinics, 3 cities

  • CES-D > 20, depression dx (Maj and Minor)

  • Minor = 4 sxs, Ham-D >9, 4 wks duration

  • Intervention: Depression Care Managers

    • Antidepressant algorithm

    • Interpersonal Psychotherapy

  • Usual Care

Bruce ML et al, JAMA

2004; 291(9): 1081-1091


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PROSPECT (IMPACT)Prevention of Suicide in Primary Care Elderly: Collaborative Trial

  • Ham-D reduction

    -Minor Depression-Not statistically significant

    38% reduction vs 34%, intervention vs usual care

Bruce ML et al, JAMA

2004; 291(9): 1081-1091


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NURSING HOME (IMPACT)MINOR DEPRESSION

  • RCT: Paroxetine vs Placebo

  • N=24 without criteria Maj. Depression

  • Mean Age: 88yrs

  • Results:No differences(CGIC, Ham D, Cornell)

    • 45% placebo response rate

  • Paroxetine - Decreased MMSE

Burrows A et al. Depress Anx 2002; 15(3):102-10


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PEARLS (IMPACT)Program to Encourage Active and Rewarding Lives for Seniors

  • RCT N=138 pts, > 59 yrs old

  • Minor Depression (51%), Dysthymia (49%)

  • PEARLS

    • Problem Solving Treatment

    • Physical and Social Activation

    • Pleasant Events Planning

    • Antidepressant Consultation

  • Versus: Usual Care

Ciechanowski P et al, JAMA

2004; 291:1569-1577


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PEARLS (IMPACT)RESULTS

  • Decrease (50% or more) depression score

    • 43% intervention group vs 15% usual care

  • Remission

    • 36% intervention group vs 12% of usual care

Ciechanowski P et al, JAMA

2004; 291:1569-1577


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Problem Solving Treatment (IMPACT)

  • 7 Steps

    • Clarify and define the problem

    • Set realistic goals

    • Generate multiple solutions

    • Evaluate and compare solutions

    • Select a feasible solution

    • Implement the solution

    • Evaluate the outcome


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Explanations/Strategies (IMPACT)

  • Placebo Response?

    • 40-50% in most, 12-15% in PEARLS

    • Watchful waiting, less specific support

      -If persistent, then specialty care

  • Setting?

    • In home vs primary care/NH

    • May not need to wait in home-bound elderly


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Prevalence and heterogeneity (IMPACT)

Major Depression Treatment

Minor Depression Treatment

Bereavement

Depression in Dementia

Response to Drug Failure


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Bereavement (IMPACT)

  • Grief

    • Can be intense, severe sadness

    • ‘Complicated’ when involving

      • Frank psychosis

      • Persistent SI

      • Marked worthlessness

      • Guilt beyond events surrounding the death

      • Major Depression beyond 2 months of death


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Bereavement Related Major Depression (IMPACT)

  • RCT, placebo controlled, N=80,

  • All subjects >/= 50yrs old.

  • Met DSM IV criteria for major depression

  • Median time from death = 32 wks.

  • 1) Nortrip. vs. 2)Nortrip + IPT vs.

    3) IPT + placebo, vs. 4) placebo

Reynolds CF et al. Am J

Psychiatry 1999;156:202-208


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Bereavement Related Major Depression (IMPACT)

  • Depression Remission:

    1) Nortrip. = 56% 2)Nortrip + IPT =69%

    3) IPT + placebo= 29% 4) placebo=45%

    *Statistically significant medication effect

  • No tx group difference in bereavement score

Reynolds CF et al. Am J

Psychiatry 1999;156:202-208


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Bereavement Summary (IMPACT)

  • Major depression syndrome common

    • Responds to antidepressant therapy

    • No clear benefit in grief sxs.

    • Role for Interpersonal Psychotherapy less clear

    • No data re: tx minor depression in bereavement


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Prevalence and heterogeneity (IMPACT)

Major Depression Treatment

Minor Depression Treatment

Bereavement

Depression in Dementia

Response to Drug Failure


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Depression in Alzheimer’s Disease (IMPACT)Sertraline

  • 12 wk Randomized, placebo controlled trial

  • N=22 Outpatients with maj. depression

    • Avg Age = 77yrs

    • Avg MMSE = 17

  • Sertraline avg dose (81mg)

    • 8-12 point decrease Cornell Scale for Depression

    • No significant change in Ham-D, Cogn, ADLs

Lyketsos et al. Am J Psychiatry

2000; 157(10): 1686-1689


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Sertraline in Severely Demented Patients (IMPACT)

  • RCT-DB, N=31 nursing home patients, 8wks

  • All stage 6 or 7 Global Deterioration Scale

  • 84% with minor depression

  • Sertraline vs. placebo

  • Cornell Scale for Depression in Dementia

    Sertraline: pre=6, post =3

    Placebo: pre=6, post=4

  • P=NS

Magai C et al. Amer

J Geriatr Psychiatry

2000;8:66-74.


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Nortriptyline in Depressed Nursing Home Residents (IMPACT)

  • RCT-DB, N=69, 8 wks

  • Regular (50mg) vs low (10mg) Nortriptyline

  • Overall: 35% responders w/ regular dose vs

    17% with low dose

  • Demented: 41% responders with low dose

Streim JE et al. Am J Geriatr Psychiatry

2000;8:150-159.


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Depression of Alzheimer’s Disease (Provisional) (IMPACT)

Olin JT et al. Am J Geriatr

Psychiatry 2002;10:125-128

1) Clinically significant depressed mood (sad, hopeless, discouraged, tearful)

2) Decreased positive affect or pleasure to social contact, usual activities

3) Social isolation or withdrawal

4) Disruption in appetite

5) Disruption in sleep

6) Psychomotor changes (e.g. agitation, retardation)

7) Irritability

8) Fatigue or loss of energy

9) Worthlessness, hopelessness, inappropriate guilt

10) Recurrent thoughts of death, suicidal ideation


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Depression of Alzheimer’s Disease (IMPACT)

  • Removal of memory/concentration item

  • Adding

    • Social isolation/withdrawal(not due to just cogn)

    • Irritability

  • 3 sxs required instead of 5

  • Sxs over 2 wks but not necessarily daily

Olin JT et al. Am J Geriatr

Psychiatry 2002;10:125-128


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Depression in Dementia Summary (IMPACT)

  • Treatment response lower

    • Different disorder? Different neuro-circuits?

  • Low dose nortriptyline more effective than regular dose nortriptyline

  • Severity matters

    • Discontinue ineffective trials in severely demented


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OVERVIEW (IMPACT)

  • Prevalence and heterogeneity

  • Major Depression Treatment

  • Minor Depression Treatment

  • Bereavement

  • Depression in Dementia

  • Response to Drug Failure


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Failed Drug Trials (IMPACT)

  • Inadequate Trial

    • Dose too low

    • Duration too short


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Inadequate Response (IMPACT)

  • Inadequate Response

    • Anything short of remission

    • Assumes Adequate Trial (Dose and Duration)


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Switching Antidepressants (IMPACT)Little to No response

INITIAL Switch To

SSRI Bupropion or Venlafaxine

Venlafaxine SSRI

Bupropion SSRI or Venlafaxine

Recommended Mirtazapine, Nortriptyline as alternatives

No Geriatric Outcome data support yet.

Pharmacotherapy of Depressive Disorders in Older Patients

Alexopoulos GS et al, Postgraduate Medicine Oct 2001


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Switching Antidepressants (IMPACT)Partial Response

Partial Response to: ADD:

SSRI Bupropion, Lithium, or Nortrip

Bupropion SSRI or Lithium

Venlafaxine Lithium

TCA Lithium or SSRI

Pharmacotherapy of Depressive Disorders in Older Patients

Alexopoulos GS et al, Postgraduate Medicine Oct 2001


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Augmentation Strategies (IMPACT)

  • Lithium

    • Start:150mg QD-BID Goal:300-900mg/day (0.4-0.8 level)

    • More supportive data than other strategies

    • More toxicity in elderly

  • Triiodothyronine(T3)

    • Start 25 mcg: Goal 50mcg

    • Negative data at < 50mcg

    • Better tolerated in elderly than Lithium


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