depression and older adults mark snowden, m.d., m.p.h. associate professor university of washington...
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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
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
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
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