University of Pittsburgh

Management of Depression in Primary Care Ellen M Whyte, MD Medical Director, Psychiatric Services UPMC Benedum Geriatric Center Medical Director Integrated Behavioral Health – Primary Care DISCLOSURES

Grant Support in last 12 months: Geriatric Workforce Enhancement Program (HRSA) U1Q HP028736 (PI: Schulz)

Off-label use of medication will be discussed.

2 LEARNING OBJECTIVES

Improve patient outcomes by identifying patients with major depression who require early psychiatric consultation.

Improve patient outcomes by utilizing measurement based, stepped care medication management in the treatment of major depression.

Improve skill in choosing and instituting pharmacotherapy for major depression.

3 PCP AS BEHAVIORAL HEALTH PROVIDERS

Most behavioral health care in the US is delivered by the primary care provider. Ø National Comorbidity Survey (2001-2003), patients reported that they received BH treatment through 40% PCP^ (PCP only >> PCP + another BH provider) 26% Psychiatrist 21% non-physician Behavioral Health provider 9% Human Services Only 3% Complementary/Alternative Medicine ^ Patients followed by PCP: typically older, female, lower SES, rural

4 Wang et al 2006 MAJOR DEPRESSIVE EPISODE

Must endorse Sadness/depressed mood and/or Loss of pleasure/anhedonia

For at least 5 total symptoms • Impaired sleep • Poor concentration • Impaired appetite • Feelings of • Low energy worthlessness or guilt • Restlessness or looking ‘slowed • Thoughts of death or down’ suicidal thoughts

At least 2 weeks duration, more days than not Causes distress or functional impairment

5 BENEFITS OF TREATMENT

Ø Improved quality of life Ø Reduced risk Ø Mitigated disability Ø Improved medical outcomes Ø Decreased health care utilization

6 MAJOR DEPRESSIVE EPISODE

Cardinal Episode in… Major Depressive Disorder Persistent Depressive Disorder (Dysthymia + Double Depression) Bipolar Disorder – Type I and Type 2 Schizoaffective Disorder

Commonly Co-Morbid with… Personality Disorders Schizophrenia and Other Psychotic Disorders Substance Abuse Dementia (Neurocognitive Disorders) TBI, CVA, Parkinson’s Dz, other neurological disorders

7 MAJOR DEPRESSIVE EPISODE

Cardinal Episode in… **Major Depressive Disorder Major Depressive Disorder with elevated suicide risk Persistent Depressive Disorder (Dysthymia + Double Depression) Bipolar Disorder – Type I and Type 2 Schizoaffective Disorder

Commonly Co-Morbid with… Personality Disorders Schizophrenia and Other Psychotic Disorders Substance Abuse **Dementia (Neurocognitive Disorders) **TBI, CVA, Parkinson’s Dz, other neurological disorders 8 Maximizing Acute Treatment Outcomes for Depression Management in Primary Care

IMPACT PROSPECT ------STAR*D Texas Medication Algorithm Project

9 PHASES OF DEPRESSION TREATMENT

Kupfer DJ. J Clin Psychiatry 1991. 10 Maximizing Acute Treatment Outcomes for Depression Management in Primary Care

Measurement Based Care

Stepped Care

Collaborative Care

11 PHQ-9

* *

12 PHQ-9

Total Score Depressive Severity

1-4 Minimal Depression

5-9 Mild Depression

10-14 Moderate Depression

15-19 Moderately Severe Depression

20-27 Severe Depression

PHQ-9 scores > 10 have a sensitivity of 88% and a specificity of 88% for Major Depressive Episode.

13 MEASUREMENT BASED CARE

Use PHQ-9 to serially monitor response to treatment.

PHQ-9 scores (as well as patient’s impression) determine next step of treatment. ------Reflected in MIPS 371 “Depression Utilization of the PHQ-9 Tool” (q 4 months while treating depression)

Flowsheet available in EPIC “PHQ-9 [1357]”

14 STEPPED CARE Medication Management is time focused and algorithm driven and leverages measurement based care. -- initiate treatment with simple medications (e.g., SSRI), but other choices may be reasonable. -- titrate to maximum tolerated doses of antidepressants quickly. -- patient status assessed at weeks 2,4,6,9,& 12 -- decision regarding continuation vs. change in medication regime every ∼ 6-8 weeks.

15 STEPPED CARE General Rule:

After 6-8 weeks at a therapeutic dose of an antidepressant, assess response and adjust treatment plan....

After an additional 6-8 weeks, assess response and adjust treatment plan...

Repeat until patient is ‘symptom free’ and enters Continuation Phase of Treatment.

16 STEPPED CARE General Rule: After 6-8 weeks at a therapeutic dose of an antidepressant….

IMPLICATION: Titrate to maximum tolerated (therapeutic) antidepressant dose quickly.

Sertraline start at 12.5-25mg/d (↑to 50mg over 1-3 weeks) start 30mg/d x 7 days, then↑ 60mg/d [or start 20mg/d x 7 d then ↑ 40mg (renal)] Mirtazapine start at 15mg/hs x 1-2 weeks, then↑30mg/hs

17 STEPPED CARE

General Rule: After 6-8 weeks…assess response and adjust treatment plan.

IMPLICATION: Response based on Ø Change in PHQ-9 scores Ø Patient’s subjective report

18 STEPPED CARE Full Response = PHQ-9 demonstrates nearly 100% resolution or symptoms and patient reports ‘back to normal’.

RECOMMENDATIONS: Ø Pt exits ACUTE treatment Ø Pt enters CONTINUATION treatment

19 STEPPED CARE Non-Response = PHQ-9 ↓ by < 30% and/or patient is reporting little to no change

RECOMMENDATIONS: Ø Switch antidepressants

Examples: SSRI à SSRI (Limit to 2 SSRI trials) SSRI à SNRI SSRI or SNRI à Mirtazapine (Remeron) SSRI or SNRI à (Wellbutrin)

20 STEPPED CARE Partial Response = PHQ-9 ↓ by > 30% and/or patient is reporting improvement RECOMMENDATIONS: Ø Watchful waiting for patients reporting near complete resolution of symptoms. Ø Dose increase (if possible) to maximum dose (e.g., 50mg à 200mg/d; mirtazapine 30mg à 45mg) Ø Augmentation with a 2nd medication with different mechanism of action Examples: SSRI/SNRI + bupropion SSRI/SNRI + mirtazapine SSRI/SNRI + atypical SSRI/SNRI + lithium 21 Discuss psychotherapy as treatment option

MOA = mechanism of action PROSPECT Algorithm STEPPED CARE: General Rule:

After 6-8 weeks at a therapeutic (max) dose of an antidepressant, assess response and adjust treatment plan....

Repeat until patient is ‘symptom free’ and enters Continuation Phase of Treatment…

or refer to psychiatry after failure of 2 – 4 treatment trials.

24 ACUTE TREATMENT- BASELINE

Patient with elevated PHQ-9 score (including mood/anhedonia)

Assess suicide risk à thoughts that life is not worth living desire for death (e.g., “wish I would not wake up”) *suicidal ideation ^suicide plan (including giving away possessions, etc) ^suicide intent

reasons for living (protective factors) *risk factors (e.g., substance abuse, interpersonal loss) history of suicide attempt ^requires emergency assessment; *consider emergency assessment 25 ACUTE TREATMENT- BASELINE Clarify diagnosis Screen for mania Screen for substance abuse Screen for psychosis (“what has been worrying you recently”)

Review prior depression tx and family hx of tx à informs medication choices

Assess for medical contributions to depression Thyroid function Sleep apnea Hypercalcemia Vit B12/ Vit D Pancreatic CA

26 SCREEN FOR HISTORY OF MANIA

All antidepressants can trigger a mania in patients with bipolar disorder who are not on a mood stabilizer. Patients tend not to remember their manias as ‘problematic’ especially early in the disease. Screening for Mania: • Mood Disorder Questionnaire (MDQ) • Bipolar Type I (mania) >> Bipolar Type II (hypomania) • In primary care, sensitivity 0.58 & specificity 0.93 • Ask about a unique period (lasting 4+ days) of • Increased energy • Increased activity +/- decreased sleep • Increased self – confidence (can lead to ‘reckless behavior’) • Abnormal elevated/irritable mood (not ‘normal self’) 27 ACUTE TREATMENT

Pharmacotherapy + Adjunct Meds Psycho-Education Support/Encouragement Psychotherapy

28 PHARMACOTHERAPY- GENERAL PRINCIPLES All antidepressants are equally effective Cannot predict which medication will work for a particular patient Ø Genetic testing can predict side effect burden. Side effects appear early & are usually transient Choose medication based on tolerability, utility of a side effect, or history of response (patient or family) Avoid abrupt discontinuation of antidepressants Ø Especially , Age alone does not dictate medication dosing

29 ANTIDEPRESSANTS

SSRI SNRI *Prozac () Effexor (venlafaxine) Luvox (fluvoxetine) Pristiq () Paxil (paroxetine) *Cymbalta (duloxetine) *Zoloft (sertraline) Fetzima () Celexa () ATYPICAL Lexapro (escitalpram) *Remeron (mirtazapine) + Viibryd () Wellbutrin (buprorion) Brintellix++ ()

+ ++ 5HT1A partial agonist; 5HT3antagonist & 5HT1A agonist

30 ANTIDEPRESSANTS

Common to All: Risk of Hypomania/Mania SSRI: nausea, diarrhea, ↑ bleeding, hyponatremia (SIADH), syndrome (rare), sexual SE SNRI: same as SSRIs plus orthostatic hypotension, hypertension, exacerbate closed angle glaucoma

Bupropion: activation/anxiety, insomnia, tremor, seizure^ (1/1000) [low incidence weight gain and sexual SE]

Mirtazapine: sedation (at lower doses), weight gain, ↑ triglycerides, [low incidence hyponatremia and sexual SE]

^SR/XL versions better tolerated, lower sz incidence 31 ANTIDEPRESSANTS

SSRI: Fluoxetine, paroxetine, -avoid in elderly d/t CYP inhibition Citalopram - monitor QTc above 20mg/d Sertraline - competes with warfarin - protein binding

SNRI: Duloxetine - renal dosing; pain benefit Venlafaxine – likely pain benefit; + orthostatic BP, HTN risk, significant withdraw syndrome

Bupropion: weight neutral; tremor, sz risk, anxiety

Mirtazapine: helps with sleep; + weight gain

32 Psycho-Education

Key points • People can and do get better: Treatment works! • Medication compliance is important; slow onset of benefit • Side effects occur early & are usually transient; can be managed • Three stages of treatment (Acute + Continuation +/- Maintenance) • Role of psychotherapy • Importance of behavioral activation (little steps) • Importance of good sleep hygiene

33 PSYCHOTHERAPY

Appropriate as treatment, without medications, for mild depression and as an adjunct to medication in moderate to severe cases. Structured, brief psychotherapies are preferred and more likely to be reimbursed by insurance companies. Likely needs to be de-mystified for patients. Safe place to tell your story Safe place to consider your options Learn skills to manage depression/anxiety 34 BRIEF STRUCTURED PSYCHOTHERAPIES

Cognitive Therapy (CBT): Identify and correct core beliefs that lead to and/or reinforce depression; alter behaviors that lead to and/or reinforce depression.

Problem Solving Therapy (PST): Reduce learned helplessness by teaching an explicit process of solving problems. Includes 6 problem solving steps plus behavioral activation.

Interpersonal Therapy (IPT): Focus on 1 of 4 areas associated with depression -- grief, role transitions, role disputes, interpersonal deficits that lead to isolation.

35 DEPRESSION MANAGEMENT

Recommendations are for contact at a minimum at 2, 4, 6, 9, 12 weeks during acute treatment.

• monitor side effects • monitor/encourage compliance • monitor response • re-assess suicide risk

Goal is complete resolution of symptoms à residual symptoms predict recurrence of depressive episode

36 PHASES OF TREATMENT

Kupfer DJ. J Clin Psychiatry 1991. 37 PHASES OF DEPRESSION TREATMENT

Acute Phase: From onset of treatment to resolution of ALL symptoms. [If medically ill, resolution of depressed mood, anhedonia, low self esteem, passive death wish/suicidal thoughts.] Continuation Phase: patients advised to remain on medications for 6-9 months AFTER resolution of ALL symptoms; followed by slow taper and discontinuation. Maintenance Phase: Prevention of recurrence after 6-9+ months symptom free.

38 PROGNOSIS

Major depression is a recurrent illness but full inter-episode remission is the norm.

~ 60% of patients who have one episode of major depression will have a 2nd episode. ~ 90% of patients who have 3 episodes of major depression will have a 4th episode. ~ 2/3 of patients have full recovery between episodes. ~ 1/3 of patients have partial recovery between episodes and are at high risk for recurrence.

39 MAINTENANCE TREATMENT - ADULTS

If first lifetime episode, uncomplicated… Ø taper & discontinue antidepressant after completion of continuation phase (at least 6 months of ‘wellness’).

If 3rd or more lifetime episode [or at least one episode with significant suicidality and/or functional impairment]… Ø indefinite continuation of ‘full dose’ antidepressant regime.

APA Practice Guidelines for Depression 2000 40 Maximizing Outcomes in Depression ACUTE TREATMENT

Measurement Based Care

Stepped (time sensitive) Care

Collaborative Care

41 Collaborative Care Model IMPACT STUDY Collaborative Care Management of Late-Life Depression in Primary Care Setting

Patients: N = 1,801; 60 + years old Inclusion Criteria: MDE (17%), Dysthymia (30%) or both

43 Unutzer et al 2002 IMPACT Results

IMPACT Usual Care N=906 N=895 Any Antidepressant Use 73% 57.2% Any Psychotherapy or 42.7%1 15.6% specialty BH visit Any Antidepressant or 82.3% 61% Psychotherapy Response 44.7% 19.2% Remission 25% 8.3% All differences statistically significant 1 30% received PST-PC; 11% met with study psychiatrist

44 Unutzer et al 2002 PROSPECT STUDY Prevention of Suicide in Primary Care Elderly: Collaborative Trial

Patients: N = 578; 60 + years old Inclusion Criteria: CES-D > 20 CES-D < 20 (5% random sample) CES-D < 20 + prior hx of depression

45 Bruce et al 2004 PROSPECT Results

Prospect Usual Care N=320 N=278 Any Antidepressant Use 66.3%^ 44.2% Psychotherapy Only 15%^ 1.3% Any Antidepressant and 6.8% 13.6% Psychotherapy Response @ 4-8-12 mo 43%^-46%^-52% 29%-36%-42%

Remission @ 4-8-12 mo 48%^-50%-55% 34%-44%-53%

^differences statistically significant

46 Bruce et al 2004 UPMC Behavioral Health Care UPMC Western Psychiatric Hospital Supports for Primary Care Providers q INTEGRATED BEHAVIORAL HEALTH SERVICE q OPTIMUM STUDY q TELEPHONIC PSYCHIATRIC CONSULTATION q GREAT-MH EVALUATION-REFERRAL PROGRAM

47 INTEGRATED BEHAVIORAL HEALTH SERVICE Collaborative Care-lite Model, started March 2015

Goal: Improve Behavioral Health access for patients w/o current BH providers by partnering with PCPs

Short –Term Model of Care: 6-10 months

Ages 18+

All diagnoses are eligible, including depression, anxiety, stress- management, etc.

48 INTEGRATED BEHAVIORAL HEALTH SERVICE

PCP identifies need Phone/email if unsure evaluation is indicated Enter EPIC Order Evaluation with Behavioral Refer to Health Specialist (LCSW) specialty or community services Brief therapy with Psychiatric Input Behavioral Health Specialist § Phone § In person

Short-term treatment completed

Back to PCP INTEGRATED BEHAVIORAL HEALTH SERVICE LocationIntegrated Providers Therapists Psychiatrist CMI Hampton L. Bonavita & A. Zajacs Umang Shah, MD CMI Absolute Justin Miller (Em Ketterer MD for RFP patients) CMI Steel City Sarah Johnson RFP Aspinwall -----

RFP Millvale Rebecca Weiss

RFP Penn Hills Kirsten Yaggi Emily Ketterer, MD CMI VFM Natrona Ben Fisher Partners-in-Health Rachel Porterfield CMI White Oak Ingrid Edwards CMI Bethel Park Kathleen Dzura Solano Ayesha Crawford Ellen Whyte, MD Health Center Assoc (Oakland) Ben Fisher CMI Monroeville x Danielle Thorpe CMI Squirrel Hill x Connie Crain INTEGRATED BEHAVIORAL HEALTH SERVICE BH Specialist Experience (Jan-June 2019) q4,516 patient visits

q30% visits were for new patients

q48% of new patients do not return: v Referral for specialized treatment v Conflict with work hours/transportation v Patient choice v Only wanted medication recommendations

51 OPTIMUM Study Optimizing Depression Tx in Older Adults When older patients don’t respond to two antidepressant trials, what should be the next step in treatment? Collaborative care approach: üPatients stay with their primary care provider. üResearch assessors measure outcomes and reports to PCPs. üGeriatric psychiatrists provide recommendations to the PCP based on a standard algorithm (bupropion, venlafaxine, aripiprazole, lithium, ) üPatients can do the entire study by phone. Collaborative Care Model OPTIMUM Study Optimizing Depression Tx in Older Adults

• Principle Investigator Jordan Karp MD • Inclusion – Age > 60 – Major Depression – Failed > 2 trials of antidepressant meds • Exclusion – Dementia – Parkinson’s Disease

If patient is interested in hearing more about the study, email study group through EPIC In Basket at P_TRD. 55 Geriatric Psychiatric Evaluation & Referral Program

Pilot Project, funded through University of Pittsburgh Department of Psychiatry Eligible Patients Aged 60+ Any Mental Health or Cognitive Concern Consult letter to PCP Referral to research studies or clinical services Marie Anne Gebara MD, lead Locations: UPMC Primary Care – White Oak & Hampton Scheduling: 412 523-3261

56 SELECTED REFERENCES

PHQ-9 Kroenke K, Spitzer RL, Williams JB: The PHQ-9 Validity of a Brief Depression Severity Measure. J Gen Intern Med. 2001 Sep; 16(9): 606–613.

MDQ Hirschfield RMA, et al: Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire. American Journal of Psychiatry, 2000, 157: 1873-1875

Hirschfield RMA. The Mood Disorder Questionnaire: A simple, paitent-rated screening instrument for Bipolar Disorder. Journal of Clinical Psychiatry Primary Care Companion 2002, 4:9-11

Hirschfield RMA, et al: Screening for Bipolar Disorder in patients treatment for depression in a family medicine clinic. JABFP 2005, 18:233-239

57 SELECTED REFERENCES

COLLABORATIVE, MEASUREMENT BASED, STEPPED CARE Bruce et al. Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA.2004 Mar 3;291(9):1081-91 [PROSPECT]

Unutzer et al. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA.2002;288(22):2836-45. [IMPACT]

Trivedi MH, Rush AJ, Crismon ML, et al. Clinical results for patients with major depressive disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry. 2004;61:669-680. [TEXAS]

Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40. [STAR*D]

American Psychiatric Association Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition, originally published in October 2010.

58 THANK YOU!

Questions?

59