Managing Depression in Primary Care Diagnosis and Treatment

Disclosure Statement of Financial Interest I, Mark Petrini, DO NOT have a financial interest/arrangement or affiliation with any organization that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Sources STAR*D Trial (2004-present) Practice Guideline for the Treatment of Patients with MDD, Third Edition. Supplement to AJP, October, 2010 Florida Best Practices for Adults with MDD 2017 2

Practice Assumptions 15 minutes/patient Infrequent visits Not in psychiatric care 3

Learning Objectives Diagnose Major Depressive Disorder Learn Evidence-based treatment Manage treatment Failure Identify and Treat MDD with Mixed Features

DEPRESSION: the NATURE OF THE BEAST PART I DEPRESSION: the NATURE OF THE BEAST MAKING THE DIAGNOSIS 4

MDD Prevalence (from NIMH) #1 cause of disability in US ages 15-44 Combined Tx + Losses = $24 billion per annum 1/12 lifetime prevalence 2015: 16.1 million adults ≥ 18 with at least one major depressive episode = 6.7% of all U.S. adults. 5

A Treatment Priority: Preserve Function & QOL Functional impairments in Work/Family Cognitive impairments/ impaired reality testing Triple rates of non-adherence to medical treatment vs. non-depressed Double annual HC costs (does not include MH costs) 6

More problems... Substance use increases 2-4 Fold  depression severity Psychosis Suicide risk Ω≈≈ 7

Making the Diagnosis Common Screening tools: Zung Self Rating Scale: 20 items Hamilton Depression Scale: 24 items PHQ-2, PHQ-9 8

The Patient Health Questionnaire-2 (PHQ-2) Over the past 2 weeks, have you been bothered by any of the following problems? Little interest or pleasure in doing things? Feeling down, depressed or hopeless? Scale: 0  3 Not at all  Nearly every day 3. > three points, proceed to PHQ-9 9

x 2 weeks, how often have you been bothered by the following problems? 7. Trouble concentrating on things, such as reading the newspaper or watching television 8. 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 9. Thoughts that you would be better off dead or of hurting yourself in some way 10. If you checked off any problems, how difficult have those problems made it for you to do your work, take care of things at home, or get along with other people? Not difficult at all ---------> Extremely difficult 1. Little interest or pleasure in doing things 2. Feeling down, depressed or hopeless 3. Trouble falling asleep, staying asleep, or sleeping too much 4. Feeling tired or having little energy 5. Poor appetite or overeating 6. Feeling bad about yourself - or that you’re a failure or have let yourself or your family down 0: Not at all 3: Nearly every day 10

MDD without PHQ Are you depressed? SIGecapS --> Sad [sic], Interest, Guilt, Suicide Changes in function? American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. Fifth Edition. Washington, DC: American Psychiatric Association 11

Depression Confounders R/O: Personality Disorder Substance use disorder OSA, insomnia BAD: rule of 4’s 12

PART II: TREATMENT 13

MDD is a thought Disorder Profound change in reality testing A “brain storm…a howling tempest…a storm of murk, intercolated with fierce waves of anxiety, despite an outward appearance of passivity, anergy.” Darkness Visible, 1990, William Styron 14

Step 1: Normalize “This is an illness, Not a change in you” “All depressed people have SIGECAPS” “SIGECAPS remit with treatment” 15

12 Month Course Acute Phase 2-3 months Continuation Phase 4-12 months Maintenance Phase vs. Taper off Ideally see/communicate with patients 2, 4, 6, 12 weeks 16

Psychotherapy TOC for Mild-Moderate MDE’s due to psychosocial stressors (e.g. bereavement, life change, etc.) Patients with Med Intolerance or Medically complicated (e.g. Pregnancy) Effective in acute, continuation, maintenance phases CBT = IPT = Psychodynamic 17

Psychotherapy Remission rates = medication remission rates “Teach someone to fish...” Enduring remission after discontinuation Remission May be maintained with MCBT

Urgently Start Medication for….. Suicidality, Psychosis Cognitive Decline Marked Changes in function Depression of long duration Persistent stressors 18

Same efficacy for all meds/classes SSRI’s SNRI’s N/DRI Other Fluoxetine 1988 Sertraline 1991 Paroxetine 1992 Citalopram 1998 Escitalopram 2002 Fluvoxamine 2007 SMS (Serotonin Modulators and Stimulators) Vortioxetine 2013 Vilazodone 2011 Venlafaxine 2000 Duloxetine 2004 Desvenlafaxine 2008 Levomilnacipran 2013 Buproprion 1985 Mirtazipine 1996 Nefazodone 1994 Trazodone 1981 Vortioxetine (Trintellix): weight neutral in studies, = placebo arm; Vilazodone (Viibryd): serotonin partial agonist; Levomilnacipran (Fetzima) is unique because it is more of an NSRI, 19

Some AD Strategies Try Maximum dose = treatment dose Use Side effects Strategically Withdrawal: some worse than others Fluoxetine = methadone MDE: is it high anxiety or low anxiety? 20

MDE with High Anxiety Psychomotor agitation Poor sleep Ruminative/obsessive thinking Choose sedating SSRI 21

Neurovegetative MDE/ Low Anxiety Hypersomnia Low energy Hyperphagia Consider Buproprion or fluoxetine 22

High Anxiety Low Anxiety SSRI’s SNRI’s N/DRI Other Fluoxetine 1988 Sertraline 1991 Paroxetine 1992 Citalopram 1998 Escitalopram 2002 Fluvoxamine 2007 SMS (Serotonin Modulators and Stimulators) Vortioxetine 2013 Vilazodone 2011 Venlafaxine 2000 Duloxetine 2004 Desvenlafaxine 2008 Levomilnacipran 2013 Buproprion 1985 Mirtazipine 1996 Nefazodone 1994 Trazodone 1981 23

Side Effects: top 4 Reasons People Quit Depression Trials GI (dyspepsia) 20%, Headache 15% Sexual SE’s 15-30%, Weight gain 20% Usually Resolve < 1 week   24

Advising about SE’s GI: wait it out, supportive measures HA: wait it out, OTC analgesics Sexual SE’s (decreased libido, anorgasmia) Weight gain: “You’re an American, self control may not come” 25

Initial Treatment Failure STAR*D trial; Biological Psychiatry 2008. non-remission after 4-6 weeks at full dose ∆ SSRI  non-SSRI ∆ non-SSRI  SSRI Remission by Switching Groups: 28% 26

Treatment Resistant Depression no remission after two AD’s: did you miss something? Treatment non-adherence? Substance use? Endocrine, OSA? BAD? Personality Disorder? Depression with Mixed Features? (See below) 27

Tx Resistant D Strategies Augment with psychotherapy SGA neuroleptics, lithium TcMS, Ketamine  ECT 28

Consult for ElectroConvulsive Therapy Severe, Refractory MDD Severe Dysfunction: psychosis or catatonia high suicide risk or Advanced eating disorders elderly

Success: Remission Continue treatment for 9 months after remission taper medication over one month; fluoxetine = Methadone Decrease talk therapy weekly, bimonthly, monthly If 3 MDE’s: 60%-80% recurrence within two years Recurrence  episode(s) severity, FH, stressors, residual symptoms 29

MDE Low Anxiety Buproprion fluoxetine High Anxiety Sedating SSRI

Partial Remission Remission ≥ 2 MDE’s, assess tx hx, FH Maximize dose Augment: psychotherapy, SGA, Lithium Remission Continuation Phase: 9-12 months 1-2 MDE’s: taper over 4-6 weeks ≥ 2 MDE’s, assess tx hx, FH

Substance Use Disorders? Personality DO? no response 4-6 weeks Reassess SSRI  Non-SSRI Non-SSRI -> SSRI Substance Use Disorders? Personality DO? BAD or Mixed Depressive Disorder? OSA, Medical Illness?

Depression with Mixed Features: New to DSM V Diagnostic battle, befogged data Undeniable Clinical Reality Can be managed in Primary care

MDD vs. BAD Two distinct Disorders? Severe Depression Mild Depression Depression Hypomania Mania

A single Spectrum Mood disorder? MDD bad

DSM V Criteria: ≥ 3 during MDE elevated or expansive mood inflated self-esteem pressured speech racing thoughts increase goal-directed activity increased risky behavior decreased need for sleep For most days x 2 weeks

Typical Clinical Presentation Poor Response to AD’s and…. high anxiety with irritability and lability Impulsivity with Irritability and Lability psychomotor agitation with Irritability and Lability

Treating MDD with Mixed Features Two Guidelines 2015 Florida Medicaid Guidelines First line = Sga’s or AD’s or mood Stabilizers, but… AD’s may destabilize, tip into Mania (6%- 11%) poor evidence for Mood stabilizers Florida Medicaid Drug Therapy Management Program for Behavioral Health. 2015 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults. University of South Florida. Sponsored by the Florida Agency for Health Care Administration. December 2015. McIntyre RS, Suppes T, Tandon R, et al. Florida best practice psychotherapeutic medication guidelines for adults with major depressive disorder. J Clin Psychiatry.

Expert consensus Guidelines (Evidence based) SGA’s = first Line Evidence for quetiapine, olanzapine, asenapine, ziprasidone, lurasidone No antidepressants first or second line Poor evidence for Mood Stabilizers Stahl SM, Morrissette DA, Faedda G, et al. Guidelines for the recognition and management of mixed depression. CNS Spectr. 2017;22(2):203–219.

Thanks to: Pri Med Department of Medicine, New York Presbyterian/ Columbia University

PMS and PMDD

ACOG Diagnostic Criteria for PMS ≥ 1 symptom 5 days before menses Symptoms must appear in three consecutive menstrual cycles:  Affective: Depression, anger, irritability, anxiety, confusion, social withdrawal  Somatic: Breast tenderness, abdominal bloating, headache, swelling of extremities    dysfunction in social or economic performance Be relieved within 4 days of menses, not recur before cycle day 13  Occur in the absence of Medication/hormone therapy, or drug or alcohol use 

PMDD Affects 3% - 8% premenopausal women ≥ 5 Emotional and Physical Symptoms ≥ 2 Menstrual Cycles Significant Functional Impairment Limited to luteal Phase, remits with menses 15% lifetime SA’s in women with PMDD, independent of MDD Remit within one week of menses

PMDD Treatment First Line: SSRI’s > SNRI’s > DNR’s Cochrane Review of 31 RCTs, 4372 participants Luteal phase only = Continuous Treatment