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

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Seda

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Α1

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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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