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LATE- LIFE DEPRESSION IN PRIMARY CARE:
The Mind Body InterfaceShilpa Srinivasan, MD, DFAPAProfessor of Clinical Psychiatry
Training Director: Geriatric Psychiatry Fellowship ProgramUSC School of Medicine
July 12, 2017
Disclosures
§ No relevant relationships to disclose.
Objectives
§ By the end of this presentation, participants will be able to:
§ Understand the prevalence and impact of depression§ Discuss medical co-morbidities that may impact
depression§ Review depressive syndromes and diagnostic
challenges§ Compare/contrast validated screening tools§ Review evidence-based treatment options
Depression is Common§ Lifetime prevalence of major depressive
disorder (MDD) in general population: 15-17% [1]
§ Frequently treated by primary care physicians
§ Up to 50% undiagnosed/untreated [2]
1. Kessler RC et al2. Pratt LA et al.
Depression in Older Adults
§ Prevalence of MDD in geriatric population: ~4% [1]
§ F>M (4.4% vs 2.7%) [2]§ 15-25% with sub-syndromic depression [3]
1. Gonzalez et al2. Steffens et al3. Mckinney et al
Depression is Costly§ Depression is 3rd leading cause of global burden of
disease§ By 2020, Major Depression will be the second leading
cause of disability worldwide [1]§ Total economic burden of MDD estimated to be $210.5
billion per year, representing a 21.5% increase from $173.2 billion per year in 2005. ú 48%-50% attributed to the workplace, including absenteeism
(missed days from work) and presenteeism (reduced productivity while at work)
ú 45%-47% are due to direct medical costs (e.g., outpatient and inpatient medical services, pharmacy costs shared by employers, employees, and society
ú About 5% of the total expenditures are related to suicide[2]
1. World Health Organization. 2. Greenberg PE et al.
Burden of Disease
Wells KB et al.
Higher costs of
ambulatory care
Decreased adherence
Loss of workplace
productivity
Increased number of
medical appointments
Increased length
of hospital stay
Healthcare Utilization
Saravay SM, et al; Verbosky LA et al; Greden JF, et al
Depression and Adherence
§ 3-fold decrease in adherenceú DM+ depressionú MI+ depressionú CAD+ depression/dysthymia
§ 4-fold higher health care costs
Katon WJ
Depression Medical Illness
§ Bi-directional relationship
ú Depression associated with poorer medical outcomes
ú Medical co-morbidities negatively impact course of depression
McKinney et al
Biologic Factors
Depression
Medical illness
Vascular risk
factors
Substance- relatedGenetics
Med-related
Depression and Medical Illness
5045
3320-30
2420
0
10
20
30
40
50
60
Hypothyroid MI Macular degeneration
Diabetes Cancer CAD
Com
orbi
dity
with
dep
ress
ion
(%)
Medical condition
Hypothyroid
MI
Mac Degen.
Diabetes
Cancer
CAD
Katon et al; Raj et al
2 to 3-fold higher rates of major depression vs. age- and gender-matched primary care patients
Post-MI Depression: Morbidity and Mortality
OR 95% CI
van Melle et al.
2.382.59
1.95
0
0.5
1
1.5
2
2.5
3
3.5
4
All-cause mortality Cardiac mortality New CV events
Depression and Diabetes: Morbidity and Mortality
0 1 2 3 4 5 6 7 8 9 10 11 12
Depression only
DM only
Depression +DM
DM only
DM only
Depression + DM
Depression + DM
1.2
1.88
2.5
1.37
9.3
2.64
11.32
Microvascular complications [1]
Macrovascular complications [1]
All-cause mortality [2]
Black et al Egede et al
HIV Statistics§ 1.1 million Americans
living with HIV§ By age, of persons
diagnosed with HIV in the United States in 2015:
§ 4% were aged 13-19 § 37% were aged 20-29 § 24% were aged 30-39 § 17% were aged 40-49
Source: CDC. Diagnoses of HIV infection in the United States and dependent areas, 2015. HIV Surveillance Report 2016;27
HIV in Older Adults
cdc.gov HIV Surveillance Report 2015;26
§ 17%: age 50+ú 12% (4,870) age 50-59 ú 5% (1,855) age 60 +
SC STD/HIV/AIDS Data 2015
SC Statistics- 2015§ AIDS prevalence:
ú SC ranked 17th in the nation (2015) (13th in 2014)
ú Columbia ranked #11ú Charleston SC #39ú Greenville #55
SC STD/HIV/AIDS Data 2015
HIV and Depression
§ Depression is the most prevalent psychiatric disorder in HIV patients
§ Lifetime rates are estimated between 35-50%
§ Depression in HIV patients correlates with poorer outcomes:ú Lower CD4 countsú Higher rates of noncomplianceú Longer time to HAART initiation ú Shorter time to AIDS diagnosis
Pyne JM et al
HIV and Depression
§ 39% of HIV infected community dwelling older adults with major depression
§ 27% considered suicide§ Stressors:
ú Less social supportú Less surviving peersú Fewer family/caregiversú Higher co-morbid health problems
Heckman et al
Risk Factors for Depression in HIV Patients
§ History of mood disorder
§ Substance abuse
§ Anxiety disorder
§ History of suicide attempt
§ Family psychiatric history
§ Polypharmacy
l Inadequate social support
l Non-disclosure of status
l Multiple losses
l Advancing illness
l Financial stressors
l Treatment failure
Psychiatric Side Effects of HAART
§ Zidovudine- confusion, agitation, insomnia, mania, depression
§ Efavirenz- confusion, stupor, agitation, amnesia, hallucinations, insomnia, abnormal or vivid dreams
§ Ritonavir- anxiety§ Didanosine- lethargy,
nervousness, anxiety, depression, psychosis
§ Stavudine sleep and mood disorders
§ Enfuvirtide- anxiety, depression
§ Steroids- mania, depression, psychosis
§ Interferon- depression, delirium
§ Interleukin-2- depression, disorientation, confusion and coma
§ Vinblastine- depression, cognitive impairment
§ Antibiotics- can often cause delirium, psychosis
DSM-5 Criteria- Major Depressive Episode
Five or more of nine symptoms present for ≥ 2 weeks . Must include symptom 1 or 2.
1. Depressed moodOR
2. Anhedonia (loss of interest)+
3. Weight change (loss or gain)4. Changes in sleep (too much or too little)5. Decreased energy6. Decreased concentration7. Psychomotor agitation or retardation8. Guilt9. Suicidal thoughts§ Must cause impairment in function§ Must not be due to medical illness/ substance use.
American Psychiatric Association, 2013
S- SleepI- InterestG- GuiltE- EnergyC- ConcentrationA- AppetiteP- PsychomotorS- Suicide
DSM-5: Other Variants
§ Persistent Depressive Disorder (Dysthymia)
§ Premenstrual Dysphoric Disorder§ Recurrent brief depression§ Substance/Medication Induced
Depressive Disorder§ Depressive Disorder due to Another
Medical Condition§ Unspecified Depressive Disorder
American Psychiatric Association, 2013
Diagnostic Challenges
Barriers
Time
Adherence
StigmaTreatment resistance
Under-diagnosis
/ mis-diagnosis
Suspect Depression in Primary Care Settings
§ Treatment resistant medical condition
§ Persistent “somatic” complaints:ú Painú Headacheú Fatigueú Insomniaú GI symptomsú Malaise
§ Frequent calls and visits for non-targeted symptoms
§ High service utilization
§ Frequent medication-related (side) effects
Depression Clues
§ Suspect in hospitalized patients:ú Post CABG, MI, strokeú Delayed recoveryú Treatment non-
adherence/ refusal§ Additional indicators:
ú Apathy, withdrawalú Irritability, isolationú Agitationú Delayed rehabilitationú Sleep disturbances
Screening Tools§ Brief tools
ú Single question regarding “depressed mood” Sensitivity 72%, Specificity 83%
ú Two-item screen- low mood and anhedonia Sensitivity 91%, Specificity 86% [1]
§ PHQ (Patient Health Questionnaire)ú Self-report tool (2 or 9 items) derived from PRIME-MDú Assessing symptoms and functional impairmentú Deriving a severity score to help select and monitor
treatment : score 5, 10, 15, 20: mild, mod, mod severe, severe
1. Mitchell AJ2. Lowe B et al. 3. Spitzer et al. 4. Kroenke K et al
Patient Health Questionnaire (PHQ-9); Screening Questions.
Over the last two weeks, how often have you been bothered by the following problems?
Not at all Several days
More than half the days
Nearly every day
A. Little interest or pleasure in doing things?
0 1 2 3
B. Feeling down, depressed of hopeless?
0 1 2 3
C. Thoughts that you would be better off dead or of hurting yourself?
0 1 2 3
A+B = PHQ-2score ≥ 3, Sensitivity 82%, Specificity 96% for MDD
Kroenke K et al
Over the last two weeks, how often have you been bothered by the following problems?
Not at all
Several days
More than half the days
Nearly every day
Feeling tired or having little energy? 0 1 2 3Poor appetite or overeating? 0 1 2 3Trouble falling or staying asleep, or sleeping too much?
0 1 2 3
Feeling bad about yourself – or that you are a failure or have let yourself or your family down?
0 1 2 3
Trouble concentrating on things, such as reading the newspaper or watching television?
0 1 2 3
Moving or speaking so slowly that other people could have noticed? Or the opposite – being so fidgety or restless that you have been moving around a lot more than usual?
0 1 2 3
If C is > 0 or A + B is 3 or greater ask the following:
Kroenke K et al.
Score ≥ 10, sensitivity 88%, specificity 88% for MDD
Screening Tools§ GDS (Geriatric Depression Scale)
ú Yes/No checklistú 30 item (long version)
sensitivity 82%; specificity 78% (21 studies) cut off score of 10
ú 15 item (short) sensitivity 84%; specificity 74% (12 studies) score >5 suggestive of depression
ú 4 and 5 item (ultra short) sensitivity 92.5%; specificity 77% (limited data, 3 studies) Cut off score of 2
Mitchell AJ et al.
U.S. Suicide Rates: Age, Race, Gender
National Center for Health Statistics
Suicide and Primary Care Contact
PCP contact All ages Age 55+Contact within 1 month 45% 58%Contact within 1 year 77% 77%
Luoma et al. 2002
• Rates increase with age (20% of suicide deaths).• Highest among Americans > 65 years• Higher correlation with depression than in younger
individuals.• Many had contact with Primary Care Provider
preceding suicide
Suicide Assessment
§ Risk Factorsú Mood disorderú Previous suicide
attempt(s)ú Chronic medical illness-
HIV, COPD, CHF, chronic pain
ú Functional impairment –feelings of guilt /burden
ú Family discordú Social isolationú Impending long term
care placement
§ Protective Factorsú Spiritual/religious beliefsú Cultural attitudes against
suicideú Social connectedness
Van Orden K et al.
Suicide Warning SignsIS PATH WARM?
Ideation - Talking about death, threatening or looking for ways to hurt self Substance Abuse - Increased alcohol or drug use Purposelessness - No reason to live, feeling no sense of purpose Anxiety - Anxious, agitated, sleep disturbance Trapped - Feeling trapped, like there’s no way out Hopelessness - Loss of hope that situation will improve Withdrawal - Withdrawal from family, friends, society Anger - Anger, rage, seeking revenge Recklessness - Engaging in risky behavior Mood Changes - Dramatic changes in mood
1. Rudd et al2. http://www.suicidology.org/c/document_library/get_file?folderId=231&name=DLFE-599.pdf.
Cognition and Depression
§ Depression associated with cognitive deficitsú Reduced processing speed, executive
dysfunction§ Dementia syndrome of depression vs co-
morbid underlying cognitive disorder§ Late-life depression associated with
increased risk of dementiaú Risk factor vs prodrome?
1. Ellison JM et al2. Barnes DE et al
Cognitive Assessment Tools
§ Folstein MMSE- 19 items, 10 minutes§ SLUMS§ MoCA
ú May better detect mild cognitive impairment than MMSE
§ Mini-Cogú 3 item recall + clock drawing if recall 1-2/3
items after 5 minú 3 minutes to administerú Sensitivity and specificity >80%
Brodaty H et al
Treatment
‘Normalcy’
Symptoms
Syndrome
Treatment phases
Response Relapse Recurrence
Recovery
Acute Continuation Maintenance
X
Seve
rity
Time
Remission
Incompleterecovery
Chronicity
Course of Depression
Kupfer & Frank
Class Agent Initial dose (mg/day)
Max. dailydose (mg)
Special dosing considerations
Gero Renal Hepatic
SSRI Citalopram 20 60 10-20 mg Avoid CrCl < 20 ml/min ↓ dose
Escitalopram 10 40 5-10 mg Avoid CrCl < 20 ml/min 10 mg
Fluoxetine 20 80 10 mg No change ↓ dose 50%
Fluoxetine weekly 90 90 90 mg Avoid Avoid
Paroxetine 20 50 10 mg 10 mg 10 mg
Paroxetine CR 25 62.5 12.5 mg 12.5 mg 2.5 mg
Sertraline 50 200 25-50 mg 25 mg ↓ dose
SNRIs Duloxetine 60 60- 120 20-40 mg Avoid CrCl < 30 ml/min Avoid
Venlefaxine 37.5 225-375 25-50 mg CrCl<=10-70, ↓dose50% ↓dose50%
Venlefaxine XR 75 225 37.5-75 mg CrCl<=10-70, ↓dose50% ↓dose50%
Desvenlefaxine 50 400 CrCl < 30, adjust dose Avoid
DNRIs Bupropion IR 100 bid 450 37.5 mg bid Limited data Severe: 75 mg qd; 100 mg qd; 150 mg q other dayBupropion SR 150 400 100 mg
Bupropion XL 150 450 150 mg
SARIs Trazodone 50 tid 600 25-50 mg No change Limited data
NaSSa Mirtazapine 15 45 7.5 mg CrCl < 40 ml/min ↓30%
TCAs Nortriptyline 25 (divided) 150 10-25 mg No change Lower dose and slower titration recommendedDesipramine 75 (divided) 300 10-25 mg
Cate
gory
Dru
g
Ant
i M1
Seda
tion
Α1
bloc
kade
Card
iac
effe
cts
GI e
ffec
ts
Seiz
ures
Wei
ght
gain
Sexu
al
SSRIs Citalopram 0 0/+ 0 0 +++ 0 0 +++
Escitalopram 0 0/+ 0 0 +++ 0 0 +++
Fluoxetine 0 0/+ 0 0/+ +++ 0/+ 0/+ +++
Paroxetine 0/+ 0/+ 0 0 +++ 0 0/+ +++
Sertraline 0 0/+ 0 0 +++ 0 0 +++
SNRIs Duloxetine 0 0/+ 0/+ 0/+ +++ 0 0/+ +++
Venlefaxine 0 0 0 0/+ +++ 0 0/+ +++
Desvenlefaxine 0 0 0 0/+ +++ 0 0/+ +++
NDRI Bupropion 0 0 0 0 ++ +++ 0 0
NaSSa Mirtazapine 0 +++ 0/+ 0 0/+ 0 0/+ 0
New Agents
§ 2011 - Vilazodone (Viibryd)ú SSRI + 5-HT1A partial agonistú Dosing; 10 mg x7 days, 20 mg x7 days, then 40 mg
qday§ 2013 -Levomilnacipran (Fetzima)
ú Enantiomer of milnacipran (Savella) which is approved for fibromyalgia
ú SNRIú Dosing 20 mg x 2days then 40 mg qday. Range 40-
120 mg/day
New Agents
§ 2013- Vortioxetine (Brintellix- now Trintellix)ú SSRI+ 5HT1A agonist, 5HT1B partial agonist,
antagonist at 5HT3, 5HT1D, 5HT7
ú Dosing: starting dose 10 mg qday, increase to 20 mg as tolerated
ú Specifically studied in elderly (5mg dose)
Rush et al, AJP 2000
STAR*DLevel 1 Initial treatment: CITALOPRAM
Level 2 Switch to: bupropion SR, Cog Tx, sertraline, venlefaxine ER
Or augment with: bupropion SR, buspirone, Cog tx
Level 2a (For those on Cog Tx in Level 2)Switch to: bupropion SR or venlefaxine ER
Level 3 Switch to: mirtazapine or nortriptylineOr augment with: lithium or triiodothyronine(only with bupropion SR, sertraline, or venlefaxine ER group)
Level 4 Switch to: tranylcypromine or mirtazapine combined with venlefaxine ER
STAR*D TRD Data
§ STAR*D:ú Stage 1: 48.6% response, 36.8% remission
ratesú Stage 2: 27.3% response, 27.0% remission
rates (switch data)ú Stage 2: 32% response; 39% remission rates
(combination with bupropion)ú Stage 3: 16.8% response, 13.7% remissionú Stage 4: 16.3% response, 13.0% remission
Rush AJ et al
PHARMACOLOGIC ALGORITHM
Apathy, retardation
Insomnia, anxiety, anorexia
Pain Atypical, melancholic, anxious
ê ê ê ê
Bupropion or Fluoxetine
Mirtazapine or Paroxetine
Duloxetine venlafaxineIf inadequate response…
ê ê
Atypical Melancholic, anxiousê ê
MAOI TCA
Initiate agent based on cost, tolerability (sertraline or citalopram)
If response is inadequate, switch or augment SSRI, OR switch class based on symptom profile (or side effect)
Kastenschmidt EK, Kennedy GJ
Clinician Response Defined by Initial PHQ-9 Score PHQ-9 Score Diagnosis/ Severity Clinician Response
1-4 None None5-9 Minimal symptoms Support, educate to call if worse;
return in 1 month10-14 Minor depression Support, watchful waiting; re-eval in 4-8
weeksDysthymia ADT/ psychotherapyMDD (mild) ADT/psychotherapy; monthly visits
15-19 MDD (moderate) ADT/ psychotherapy; visits or phone contact q 2-4 weeks
≥20 MDD (severe) Immediate initiation of ADT and, if severe impairment or poor response to therapy, expedited referral to mental health for psychotherapy and/or collaborative management
Kroenke K, Spitzer RL
Clinician Response Defined by Subsequent Score on the PHQ-9 after 4-6 Weeks of Antidepressant Treatment at
Recommended Dose.
PHQ-9 Score or Change Outcome Clinician Response
Drop of 1 point OR No decrease OR increase
Non-response Increase dose: Augmentation; Switch; Informal or formal psychiatric
consultation; Add psychotherapy? IN PATIENT ADMISSION
2-4 points decrease Partial response Increase ADT dose/ augmentation
5 or more point decrease Response Maintain medicationFollow up in 4 weeks
PHQ-9 ≤ 4-5 Remission Maintain medicationFollow up in 4 weeks
Adapted from Oxman TE. Re-Engineering Systems for Primary Care Treatment of Depression; The Respect Depression Care Process supervising psychiatrist manual. Trustees of Dartmouth College, 2003
Psychotherapy modalities
§ Interpersonal psychotherapy§ Cognitive behavioral therapy§ Problem-solving therapy§ Behavioral therapy§ Brief focused psychodynamic therapy§ Family therapy§ Psycho-education
Psychotherapy as Monotherapy
§ Consider for:ú (Out)-patients with mild to moderate
depression.ú Patients who cannot/ will not take medication.ú Patients with predominant psychosocial
stressors.ú Patients with dysthymia or personality
disordersú Patients without psychotic features or suicidal
ideation.
Mental Health Referral
§ Unclear diagnosis§ Evidence of psychotic features§ History of bipolar symptoms (mania,
hypomania)§ Concomitant substance use§ Signs of comorbid psychiatric conditions§ Need for psychosocial interventions§ Treatment resistance§ Patient preference
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April 9,2014.2. Kessler RC et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey
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Control and Prevention; 2008. NCHS Data Brief. 1-2-2013.4. Gonzalez O et al. Current depression among adults- United States 2006 and 2008. MMWR Morb Mortal Wkl Rep
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Psychiatry 2000;57(6) 601-7.6. McKinney BC et al. The age-by-disease interaction of late-life depression. Am J Geriatr Psychiatry 2012;10: 1-15.7. Blazer DG, Depression in late life: review and commentary. J Gerontol A Biol Sci Med Sci, 2003. 58(3): p. 249-65.8. Djernes, JK, Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatr Scand, 2006.
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