1. Managing Depression in Primary Care
Diagnosis and Treatment

2. 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.

3. 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

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

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

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

7. 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: million adults ≥ 18 with at least one major depressive episode =
6.7% of all U.S. adults. 5

8. 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

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

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

11. 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:  3
Not at all  Nearly every day
3. > three points, proceed to PHQ-9 9

12. 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 : Nearly every day 10

13. 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

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

15. PART II: TREATMENT 13

16. 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

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

18. 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

19. 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

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

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

22. 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

23. 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

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

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

26. 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

27. 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

28. 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

29. 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

30. 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

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

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

33. 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

34. MDE
Low Anxiety
Buproprion
fluoxetine
High Anxiety
Sedating SSRI

35. 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

36. 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?

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

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

39. A single Spectrum Mood disorder?
MDD bad

40. 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

41. 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

42. 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 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.

43. 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.

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

45. PMS and PMDD

46. 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 

47. 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

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