Depression and Older Adults

Mark Snowden, M.D., M.P.H.Associate Professor University of WashingtonMedical Director Geriatric Psychiatry ServicesHarborview Medical Center

OVERVIEW

• Prevalence and heterogeneity• Major Depression Treatment• Minor Depression Treatment• Bereavement• Depression in Dementia• Response to Drug Failure

1 YR PREVALENCE AFFECTIVE DISORDER

Age (yrs) Odds Ratio

15-2415-24

25-3425-34

35-4435-44

45-5445-54

1.67*1.67*

1.321.32

1.351.35

1.01.0

* p<.05* p<.05(Kessler,RC et al. Arch Gen Psych Jan. ‘94)(Kessler,RC et al. Arch Gen Psych Jan. ‘94)

COHORT DEPRESSION RATES

.14

Cumulative

Depression

Rate .07

Age (yrs)Age (yrs)1414 2424 3434 4444 5454 6464 7474

00

1955-641955-64

1945-541945-54

1935-441935-44

1925-341925-34

1915-241915-24

1905-141905-14

PREVALENCE OF DEPRESSION IN GERIATRIC POPULATIONS

Setting Maj. Depr.

CommunityCommunity

Med. ClinicsMed. Clinics

Nursing Homes Nursing Homes

1 - 4%1 - 4%

5 - 10%5 - 10%

12 - 20%12 - 20%

PREVALENCE OF DEPRESSION IN GERIATRIC POPULATIONS

Setting Maj. Depr. Depr. Sxs.

CommunityCommunity

Med. ClinicsMed. Clinics

Nursing Homes Nursing Homes

1 - 4%1 - 4%

5 - 10%5 - 10%

12 - 20%12 - 20%

8 - 16%8 - 16%

17 - 35%17 - 35%

30 - 45%30 - 45%

Differential DiagnosisMaj. Depression (Partial Remission)

Dysthymia

Minor Depression

Adj. Disorder w/ depressed mood

Mood Disorder due to Medical Condition

Depression of Alzheimer’s Dementia

Bereavement

DSM IV MAJOR DEPRESSION CRITERIA

1) Depressed Mood

and/or

2) Anhedonia

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

Late Onset vs Early Onset Depression

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* P<.05

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

N=246N=246

OVERVIEW

• Prevalence and heterogeneity• Major Depression Treatment• Minor Depression• Bereavement• Depression in Dementia• Response to Drug Failure

NEW GENERATION ANTIDEPRESSANTS

• Selective Serotonin Re-uptake Inhibitors– Fluoxetine (Prozac)– Sertraline (Zoloft)– Paroxetine (Paxil)– Citalopram (Celexa)– Escitalopram (Lexapro)

SSRIs

• More Alike than Different

• Half Life:

Fluoxetine>>citalopram>sertraline=paroxetine

• Anticholinergic:

Paxil mild > fluoxetine, sertraline, citalopram

• Drug Interactions:

Fluoxetine > paroxetine > sertraline, citalopram

NEW GENERATION ANTIDEPRESSANTS

• Bupropion (Wellbutrin)

• Venlafaxine (Effexor)

• Duloxetine (Cymbalta)

• Mirtazepine (Remeron)

BUPROPION

• Different, Unknown therapeutic mechanism

• Stimulant-like structure

• Seizure Risks/Contraindication

VENLAFAXINE XR

• Low Dose: Serotonergic> Noradrenergic

• Higher Dose: More combination 5HT & NE

• Fewer Drug-Drug Interactions than SSRIs

• Hypertension Side Effect

Duloxetine

• Combined Serotonergic and Noradrenergic

• Decreased Risk Hypertension

• Some efficacy for neuropathic pain

MIRTAZEPINE

• Serotonergic and Noradrenergic mechanisms

• Mild-moderate sedation

• Associated with some weight gain

TRICYCLIC ANTIDEPRESSANTS

• Tertiary (amitriptyline, imipramine, doxepin)

• Secondary(nortriptyline, desipramine)

• Secondary have fewer side effects

Anticholinergic: desipramine < nortriptyline

Orthostatic Hypotension: nortriptyline < desipramine

Sedation: nortriptyline > desipramine

OTHER CONSIDERATIONS

• Sedation– more with mirtazepine

• Sexual Dysfunction– less with bupropion

• Hypertension Risk– venlafaxine

• Seizure History– bupropion contraindicated

GERIATRIC DOSING

NortriptylineFluoxetineSertralineParoxetineCitalopramDuloxetineBupropionVenlafaxineMirtazepine

___Initial (mg)__

10102510102075

37.515

Est. therapeutic Dose

50-12510-40

50-20020-6020-4040-60

200-450150-375

30-45

Antidepressant Duration

• Low Dose: 1-2 wks before change

• Intermediate dosing: 2-4 wks

• Maximum Dose: 4-6 wks

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

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.

Intervention Example:Depression Care Management (Clinic)

Improving Mood-Promoting Access to Collaborative Treatment (IMPACT)

• 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

Unutzer J et al. JAMA2002;288:2836-2845

IMPACT OUTCOMES12 Months

0

10

20

30

40

50

60

50% HSCL reduction Remission

IMPACTUsual Care

%

45

1925

8

• Prevalence and heterogeneity• Major Depression Treatment• Minor Depression Treatment• Bereavement• Depression in Dementia• Response to Drug Failure

Minor DepressionResearch Criteria for Further

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

• Depressed Mood or Anhedonia

• No hx major depression, Mania

• Not Dysthymic

Minor Depression and Dysthymia 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

Minor Depression and Dysthymia 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

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

HSCL-D-20 Scores by Treatment Assignment

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

HSCL-D-20 Scores of Patients With Minor Depression

Remission Rate

• Minor Depression– Paroxetine 53% PST 44% Placebo 49%

• Dysthymia– Paroxetine 46% PST 51% Placebo 40%

No treatment statistically significant vs Placebo

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

PROSPECTPrevention 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 CareBruce ML et al, JAMA 2004; 291(9): 1081-1091

PROSPECTPrevention 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

NURSING HOMEMINOR 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

PEARLSProgram 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 CareCiechanowski P et al, JAMA2004; 291:1569-1577

PEARLSRESULTS

• 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, JAMA2004; 291:1569-1577

Problem Solving Treatment

• 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

Explanations/Strategies

• 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

Prevalence and heterogeneityMajor Depression TreatmentMinor Depression TreatmentBereavementDepression in DementiaResponse to Drug Failure

Bereavement

• 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

Bereavement Related Major Depression

• 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 JPsychiatry 1999;156:202-208

Bereavement Related Major Depression

• 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 JPsychiatry 1999;156:202-208

Bereavement Summary

• 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

Prevalence and heterogeneityMajor Depression TreatmentMinor Depression TreatmentBereavementDepression in DementiaResponse to Drug Failure

Depression in Alzheimer’s DiseaseSertraline

• 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 Psychiatry2000; 157(10): 1686-1689

Sertraline in Severely Demented Patients

• 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. AmerJ Geriatr Psychiatry2000;8:66-74.

Nortriptyline in Depressed Nursing Home Residents

• 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.

Depression of Alzheimer’s Disease (Provisional)

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

Olin JT et al. Am J GeriatrPsychiatry 2002;10:125-128

Depression of Alzheimer’s Disease

• 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 GeriatrPsychiatry 2002;10:125-128

Depression in Dementia Summary

• 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

OVERVIEW

• Prevalence and heterogeneity• Major Depression Treatment• Minor Depression Treatment• Bereavement• Depression in Dementia• Response to Drug Failure

Failed Drug Trials

• Inadequate Trial– Dose too low– Duration too short

Inadequate Response

• Inadequate Response– Anything short of remission– Assumes Adequate Trial (Dose and Duration)

Switching AntidepressantsLittle 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 PatientsAlexopoulos GS et al, Postgraduate Medicine Oct 2001

Switching AntidepressantsPartial 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 PatientsAlexopoulos GS et al, Postgraduate Medicine Oct 2001

Augmentation Strategies

• 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