Sponsorship and Supportdepression in clinical practice. •Recognize the relationship between depression and cognitive ... •No 2 people will have the exact same signs and symptoms

Sponsorship and Support

This activity is supported by an educational grant from Takeda Pharmaceuticals USA, Inc.

This educational activity is provided by the North Carolina Academy of Family Physicians in collaboration with Med‐IQ.

Copyright© 2020 Med‐IQ, Inc.

William Clay Jackson, MD, DipTh, FAAFP (Chair)Clinical Assistant Professor, Department of Family Medicine and PsychiatryAssociate Director, Palliative Medicine FellowshipUniversity of Tennessee College of MedicineMemphis, TN

Michael Edward Thase, MD (Chair)Professor, Department of PsychiatryPerelman School of Medicine of the University of PennsylvaniaPhiladelphia, PA

FacultyJames Sloan Manning, MD (Presenter)Family Medicine PhysicianNovant HealthGreensboro, NC

Disclosure StatementThe content of this activity has been peer reviewed and has been approved for compliance. The faculty and contributors have indicated the following financial relationships, which have been resolved through an established COI resolution process and have stated that these reported relationships will not have any impact on their ability to give an unbiased presentation.

James Sloan Manning, MD, has indicated no real or apparent conflicts.

William Clay Jackson, MD, DipTh, FAAFPConsulting fees/advisory boards: Allergan, Inc., Otsuka America Pharmaceutical, Inc., Pfizer, Inc., Sunovion Pharmaceuticals Inc.

Michael Edward Thase, MDConsulting fees/advisory boards: ACADIA Pharmaceuticals Inc., Akili Interactive Labs, Inc., Alkermes, Allergan, Inc., Janssen Pharmaceuticals, Inc., Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Merck & Co., Inc., Otsuka America Pharmaceutical, Inc., Pfizer, Inc.Spouse Salary: Peloton Advantage

Reference of unlabeled/unapproved off label drug uses or products are mentioned in this presentation.

The peer reviewers and activity planners have no financial relationships to disclose.

Learning ObjectivesUpon completion, participants should be able to:• Apply clinical recommendations and practical methods to screen for depression in clinical practice.

• Recognize the relationship between depression and cognitive impairment and implement tools to assess cognitive impairment.

• Identify depression treatment and monitoring strategies that take into account patients’ treatment goals and preferences.

• 47‐year‐old woman – Type 2 diabetes– Overweight (BMI = 29.8 kg/m2) – Fasting blood sugar levels have slowly worsened over the past 5 years

• During her exam, she mentions:– Frequently feeling tired despite getting 7+ hours of sleep/night – Difficulty concentrating at work, which affects her job performance

• She wonders whether these problems are related to her diabetes

Patient Case: Meet Ms. Johnson

Could Ms. Johnson have depression?

• No 2 people will have the exact same signs and symptoms• Some people are not even aware of feeling sad, down, or “blue”• It is useful to think of symptom clusters or domains:

– Psychological/emotional– Physical– Cognitive

Heterogeneity of Depressive Syndromes

APA. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013.

• Psychological/emotional– Depressed mood, sadness, hopelessness– Anhedonia– Guilt, worthlessness, suicidal thoughts




• Physical– Changes in sleep, changes in appetite, fatigue, pain




• Physical– Changes in sleep, changes in appetite, fatigue, pain

• Cognitive– Impaired concentration and memory, indecision– Psychomotor retardation (slowed mentation)



The Burden of DepressionWhat Family Physicians Need to Know

• 2017 past‐year prevalence estimates for experiencing one or more major depressive episodes1– 17.3 million adults in the US, or 7.1% of all US adults– 3.2 million adolescents aged 12 to 17 in the US, or 13.3% of US adolescents

• Adults and adolescents frequently experience severe impairment1

• Depression is a leading cause of disability in the US, second only to musculoskeletal disorders2

• 30%‐70% of those who die by suicide have a depressive disorder3

Depression Is Prevalent and Disabling

1. NIMH. www.nimh.nih.gov/health/statistics/major‐depression.shtml;2. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Lancet. 2016;388:1545‐602;

3. Mental Health America. www.mentalhealthamerica.net/suicide.

36%

64%

Adolescents

29%

71%

Adults

With severe impairmentWithout severe impairment

What Kind of Healthcare Providers Do Mental Health Patients See?

Wang PS, et al. Arch Gen Psychiatry. 2005;62:629‐40.

12.3%16.0%

22.8%

8.1% 6.8%Patie

nts, %

Psychiatrist Non‐PsychiatristMental Health

Specialist

General MedicalClinician

Human ServicesResource

Complementary &Alternative Medical

Clinician

Healthcare Clinician(Treatment could be sought from > 1 source)

5

10

15

20

25

0

Underrecognition and Undertreatment of MDD in Primary Care (Mathematical Model)

Pence BW, et al. Curr Psychiatry Rep. 2012;14:328‐35.

Primary Care Population

MDD Prevalence12.5%



MDD Population

Recognized clinically Unrecognized

47%

MDD Population

Any treatment No treatment

24%



9%



MDD Population

9%Adequate treatmentNo/inadequate treatment



MDD Population

Symptom remission No remission

6%

New Zealand2,b

MDD “Prevalence” Increases With Careful, Prospective Assessment

Seek and Ye Shall Find

1. Kessler RC, et al. JAMA. 2003;289:3095‐105; 2. Jaffee SR, et al. Arch Gen Psychiatry. 2002;59:215‐22.

40

35

30

20

10

0

25

15

5

RetrospectiveAssessment

ProspectiveAssessment

USA1,a

Major Dep

ression

Lifetim

e Prevalen

ce, %

aDoes not include Alaska and Hawaii.bIncludes only the South Island.

25%

37%

38% Receiving evidence‐based therapyNo medication or psychotherapyInadequate treatment

Even Adults With Severe Symptomsa Often Do Not Receive Optimal Care

aSevere symptoms defined as PHQ‐9 score > 20. Shim RS, et al. J Am Board Fam Med. 2011;24:33‐8.

Screening for Depression Best Practices for Family Physicians

• For adults, including pregnant and postpartum women:– Improves the identification of depression– When combined with adequate support systems, improves clinical outcomes

• For screen‐positive adults and older adults:– Treatment with antidepressants, psychotherapy, or both decreases clinical morbidity

• For screen‐positive pregnant and postpartum women:– CBT improves clinical outcomes

• Little to no associated risk

Benefits of Screening in Primary Care: USPSTF

Siu AL, et al. JAMA. 2016;315:380‐7.

1. Screening across adult care settings, regardless of risk factors2. Optimal timing and interval remains to be determined3. Pragmatic approach

– Screen all adults who have not been screened previously– Use clinical judgment around risk factors, comorbid conditions, and life events to determine whether additional screening is warranted for high‐risk patients

Who and When to Screen: USPSTF

Siu AL, et al. JAMA. 2016;315:380‐7.

• Ms. Johnson is a 47‐year‐old woman with type 2 diabetes• She frequently feels tired despite getting 7+ hours of sleep/night • She has been having trouble concentrating at work lately, and she is worried that it is affecting her job performance and credibility with her coworkers and supervisor

Patient Case: Assessing Ms. Johnson for MDD

What is the best way to further assess for MDD?

• Patient Health Questionnaire 9 (PHQ‐9)• Hospital Anxiety and Depression Scale in adults• Geriatric Depression Scale in older adults• Edinburgh Postnatal Depression Scale in postpartum and pregnant women

Commonly Used Screening Instruments: USPSTF

Siu AL, et al. JAMA. 2016;315:380‐7.

PHQ‐9: As Easy as Possible

Kroenke K, et al. J Gen Intern Med. 2001;16:606‐13.

Over the LAST 2 WEEKS, how often have you been bothered byany of the following problems? Not at all Several days

More than half the days

Nearly every day

1. Little interest or pleasure in doing things 0 1 2 32. Feeling down, depressed, or hopeless 0 1 2 33. Trouble falling or staying asleep, or sleeping too much 0 1 2 34. Feeling tired or having little energy 0 1 2 35. Poor appetite or overeating 0 1 2 36. Feeling bad about yourself—or that you are a failure or have let

yourself or your family down 0 1 2 3

7. Trouble concentration on things, such as reading the newspaper or watching television 0 1 2 3

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

0 1 2 3

9. Thoughts that you would be better off dead or of hurting yourself in some way 0 1 2 3

Developed by Spitzer RL, Williams JBW, Kroenke K, et al.

• One‐half of primary care patients with MDD have comorbid anxiety1

• Generalized Anxiety Disorder 7‐item (GAD‐7) scale2– Validated screening tool in primary care2

– Sensitive to change over time, can be used to monitor symptom severity3

Anxiety and MDD

1. Gaynes BN, et al. Ann Fam Med. 2007;5:126‐34; 2. Spitzer RL, et al. Arch Intern Med. 2006;166:1092‐7; 3. Kertz S, et al. Clin Psychol Psychother. 2013;20:456‐64.

Over the LAST 2 WEEKS, how often have you been bothered by any of the following problems? Not at all Several days

More than half the days

Nearly every day

1. Feeling nervous, anxious, or on edge 0 1 2 32. Not being able to stop or control worrying 0 1 2 33. Worrying too much about different things 0 1 2 34. Trouble relaxing 0 1 2 35. Being so restless that it’s hard to sit still 0 1 2 36. Becoming easily annoyed or irritable 0 1 2 37. Feeling afraid as if something awful might happen 0 1 2 3

• Present in 20%‐40% of patients with MDD1‐3

• Includes deficits in3,4– Attention– Verbal and nonverbal learning– Short‐term and working memory– Visual and auditory processing– Problem solving– Processing speed– Motor function – Executive function (i.e., ability to formulate goals, plan, and perform effectively)

Cognitive Impairment and MDD

1. Gualteri CT, et al. J Clin Psychiatry. 2008;69:1122‐30; 2. McIntyre RS, et al. Depress Anxiety. 2013;30:6:515‐27; 3. Lam RW, et al. Can J Psych. 2014;59:649‐54; 4. Alves MRP, et al. CNS Neurol Disord Drug Targets. 2014;13:1026‐40.

• Depression has a more profound effect than aging on overall memory accuracy and processing speed1,2

• There is correlation between cognitive dysfunction and MDD severity3

• Patients with MDD and high levels of anxiety are more likely to experience subjective cognitive dysfunction4

• Cognitive performance predicts depressive symptoms at baseline and at 12‐month follow‐up in first‐episode patients5

• Treatments have differing effects5

• Executive function predicts functioning in patients with remitted MDD6

Cognitive Impairment and MDD

1. Sejunaite K, et al. Psychiatry Res. 2018;261:456‐63; 2. Albert KM, et al. Depress Anxiety. 2018;35:694‐9; 3. McIntyre RS, et al. CNS Spectr. 2016;21:362‐6; 4. Cha DS, et al. J Affect Disord. 2018;238:228‐32;

5. Baune BT, et al. Inter J Neuropsychopharmacol. 2018;21:97‐107; 6. Knight MJ, et al. J Affect Disord. 2018;235:129‐34.

• Conventional depression rating scales do not assess cognition1

• Subjective tools – BC‐CCI: British Columbia Cognitive Complaints Inventory2

– CPFQ: Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire3,4

– PDQ: Perceived Deficits Questionnaire1,5

• Composite objective and subjective tool1– THINC‐it®

Cognitive Tools Available for Office Screening

1. Ragguett RM, et al. Evid Based Mental Health. 2016;19:106‐9; 2. University of British Columbia. https://workingwithdepression.psychiatry.ubc.ca/leaps/the‐british‐columbia‐cognitive‐complaints‐inventory‐bc‐cci; 3. Russo M, et al. Depress

Anxiety. 2015;32:262‐9; 4. Fava M, et al. Psychother Psychosom. 2009;78:91‐7; 5. Lam RW, et al. Value Health. 2013;16:A330.

Due to copyright laws, the image on this slide cannot be reproduced. Please refer to the website referenced below if you wish to access the tool for individual clinical use.

A Cognitive Screening Tool: BC‐CCI

Tool available at https://workingwithdepression.psychiatry.ubc.ca/files/2013/07/BC‐CCI‐Expanded‐2013.pdf.

Managing DepressionAligning Treatment Goals and Patient Expectations

• Ms. Johnson’s PDQ results suggest that she’s having trouble focusing and sustaining attention

• A referral to a clinical psychologist for cognitive testing yields similar results

• Would you recommend any additional testing?– What about neuroimaging?

Patient Case: Using Screening Results for Treatment Planning

Pharmacologic1 Psychotherapy2,3Other Nonpharmacologic

Treatments1,2,4

Antidepressants CBT ExerciseAugmentation (e.g., lithium, T3,a atypicals)

Interpersonal therapy Electroconvulsive therapy

Psychedelics (e.g., ketaminea) Mindfulness‐based cognitive therapy

Phototherapy

Vagus nerve stimulationRepetitive transcranial magnetic stimulation

Management Strategies for MDD

1. VandenBerg AM, et al. In: DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. 2020; 2. Loosen PT, et al. In: Ebert MH, et al, eds. Current Diagnosis & Treatment: Psychiatry. 2nd ed. 2008;

3. MacKenzie MB, et al. Neuropsychiatr Dis Treat. 2018;14:1599‐605; 4. Golden RN, et al. Am J Psychiatry. 2005;162:656‐62.aOff‐label use.

Modalities for Acute‐Phase MDD Treatment

APA. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf.

Due to copyright laws, the table on this slide cannot be reproduced. Please refer to the article referenced below if you wish to access the table.

Remission and Response in MDD: Goals of Treatment

Trivedi MH, et al. Am J Psychiatry. 2006;163:28‐40.

Response 50% decrease in baseline depression scoresRemission Being virtually asymptomatic for 2 consecutive weeks:

• Hamilton Depression Rating Scale (HDRS) score ≤ 7• PHQ‐9 score < 5• Quick Inventory of Depressive Symptomatology–Self‐Report

(QIDS‐SR) score ≤ 5

Partial remission is associated with:• Significant and persisting social and occupational function

impairment• Increased risk of relapse• Increased chronicity of depressive episodes• Shorter durations between episodes• Increased all‐cause mortality• Increased risk of suicide

The Importance of Attaining and Maintaining Remission—Why We Care

Romera I, et al. Eur Psychiatry. 2010;25:58‐65; Thase ME. J Clin Psych. 2009;70:4‐9.

• For most patients, remission requires repeated trials of “sustained, vigorously dosed” antidepressant medication

• If the first pharmacologic treatment fails, switch or augment– Both approaches are reasonable

• Likelihood of achieving remission substantially decreases after 2 adequate drug trials– Suggests need for more complicated regimens, nonpharmacologic combinations, and/or psychiatric consultation

Achieving Remission in the “Real World”

Gaynes BN, et al. Cleve Clin J Med. 2008;75:57‐66.

• Is collaborative– Allows patients and their providers

to make decisions together – Takes into account: Best scientific evidence available Patient’s values and preferences

• Honors– Provider’s expert knowledge– Patient’s right to be fully informed of

all care options and their potential harms and benefits

• Provides patients with support to make the best individualized care decisions

• Allows providers to feel confident in the care they prescribe

Working Together to Pick the Best Treatment: What Is Shared Decision Making?

Informed Medical Decisions Foundation. AHRQ. https://innovations.ahrq.gov/qualitytools/informed‐medical‐decisions‐foundation‐tools‐providers.

• Preference predicts both therapeutic alliance and attrition in treatment for depression

• Matching patients who have a treatment preference to the treatment they prefer yields better outcomes than a mismatch– Patients who favorably endorsed psychosocial strategies indicated a preference for psychotherapy and a rejection of antidepressant medication

– Endorsement of a biomedical explanation of depression was associated with preference for antidepressant medication

Begin With Learning Your Patient’s Treatment Preferences and Past Experiences

Steidtmann D, et al. Depress Anxiety. 2012;29:896‐905.

Commonly Used Antidepressants

VandenBerg AM, et al. In: DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. 2020;Anderson IM, et al. J Psychopharmacol. 2008;22:343‐96.

Drug Class and Representative Agents Select Safety and Efficacy Information for the ClassSelective serotonin reuptake inhibitors (SSRIs)Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

Comparable efficacy to other classes Side effects include GI symptoms, anxiety, headache, somnolence, insomnia, and

sexual dysfunction Serotonin‐norepinephrine reuptake inhibitors (SNRIs)Newer‐generation agents:desvenlafaxine, duloxetine, venlafaxine, levomilnacipran

May have modestly greater efficacy than SSRIs Safety similar to SSRIs (nausea, sexual dysfunction, activation; also increased

sweating, hypertension) More severe discontinuation/withdrawal syndrome than with SSRIs

Tricyclic antidepressants (TCAs):amitriptyline, desipramine, doxepin, imipramine, nortriptyline

Comparable efficacy to SSRIs but with known side effects, such as anticholinergic effects, sedation, weight gain, sexual dysfunction, and orthostatic hypotension

Monoamine oxidase inhibitors (MAOI)Phenelzine, selegiline,atranylcypromine, isocarboxazid

More effective than TCAs for atypical symptoms of depression Side effects include orthostatic hypotension, weight gain, and sexual side effects

aOff‐label use.

Commonly Used Antidepressants

VandenBerg AM, et al. In: DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. 2020.

Drug Class and Representative Agents Select Safety and Efficacy Information for the Class

Norepinephrine and dopamine reuptake inhibitor (NDRI)Bupropion One of the most activating antidepressants; may be useful for decreased motivation,

low energy, and fatigue Side effects include nausea, vomiting, tremor, insomnia, and dry mouth

Mixed serotonergic effects (Mixed 5‐HT)Vilazodone, vortioxetine SSRI and 5‐HT1A partial agonists

Vortioxetine is also a 5‐HT3, 5‐HT1D, and 5‐HT7 antagonist and 5‐HT1B partial agonist; may have fewer cognitive side effects than other agents

Side effects similar to those of SSRIs

Presenting symptoms• Prior positive response• Response in other family members

• Short‐term side effects• Long‐term side effects• Interaction with nonpsychiatric medication(s)

• Patient preference • Patient age• Cost of medication• Concurrent medical disorders• Concurrent psychiatric disorders

Considerations in Medication Selection

VandenBerg AM, et al. In: DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. 2020.

• Limited efficacy– 50%‐60% intention‐to‐treat response rates– ~10%‐20% advantage vs placebo

• Intolerable side effects for 10%• Inconsistent effects on key symptoms (e.g., insomnia, anxiety, cognition)

• Relatively slow onset of action for some patients

Limitations of Conventional Antidepressant Medication

Thase ME. Curr Psychiatry Rep. 2011;13:476‐82; Connolly KR, et al. Drugs. 2011;71:43‐64;VandenBerg AM, et al. In: DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. 2020.

Antidepressants and Cognition

1. Herrera‐Guzman I, et al. J Psychiatr. 2009;43:855‐63; 2. Herrera‐Guzman I, et al. Psychiatry Res. 2010;177:323‐9; 3. Bortolato B, et al. BMC Med. 2016;14:9;

4. Kaser M, et al. Psychol Med. 2017;47:987‐9; 5. McIntyre RS, et al. Int J Neuropsychopharmacol. 2014;17:1557‐67;

6. Das S, et al. Ther Adv Psychopharmacol. 2016;6:39‐54.

Agent Therapeutic Class Effects on CognitionEscitalopram1,2 SSRI Working and episodic memory, executive functionDuloxetine1,2 SNRI Working and episodic memory, processing speed,

executive functionBupropion3 NDRI Immediate, delayed verbal and nonverbal memoryVortioxetine4,5 Mixed 5‐HT Overall improvement (across domains)Brexpiprazole6 Second‐generation

antipsychoticImprovement in patients with schizophrenia

Meta‐Analysis of Antidepressant Effects on DSST in Patients With MDD1

1. Adapted with permission from Baune BT, et al. Int J Neuropsychopharmacol. 2018;21:97‐107; 2. US FDA. www.fda.gov/media/77404/download.

Due to copyright laws, the image on this slides cannot be reproduced. Please refer to the article referenced below if you wish to access the figure.

0

0.1

0.2

0.3

0.4

0.5

0.6

DUL VOR 10/20 DUL VOR 5 mg VOR 10 mg VOR 20 mg

Vortioxetine Therapy Improves DSST Performance in 3 Clinical Trials of MDD

1. Mahableshwarkar AR, et al. Neuropsychopharmacol. 2015;40:2025‐37; 2. Katona C, et al. Int Clin Psychopharmacol. 2012;27:215‐23; 3. McIntyre RS, et al. Int J Neuropsychopharmacol. 2014;17:1557‐67; 4. Harrison JE, et al. Int J Neuropsychopharmacol. 2016;pyw054; 5. US FDA. www.fda.gov/media/77404/download.

DSST – Replication: Number of correct symbols, change from baseline at week 8DSST measures executive functioning, working memory, attention, and speed of processing4

The effect of vortioxetine on DSST performance is not mediated solely through an improvementin general depressive symptoms (measured by MADRS/HAM‐D24)1,2

Limitations: May include patients without clinically relevant cognitive dysfunction due to lack of diagnostic criteria; duration of treatment. Common adverse events with vortioxetine include: nausea, headache, diarrhea, dry mouth, constipation, hyperhidrosis, and somnolence.1‐3Risks: Prescribing information for all antidepressants contain a boxed warning regarding increased risk of suicidal thoughts/behavior in children, adolescents, and young adults. Patients of all ages should be monitored closely for worsening of symptoms and suicidal thoughts/behaviors.

Stan

dardize

d Effect Size

vs P

lacebo

aP < .05 bP < .001

n = 187 n = 175 n = 136n = 128 n = 204N = 193

Connect1(ANCOVA, OC, LS means)

Elderly2(ANCOVA [FAS], LOCF)

FOCUS3(FAS, MMRM)

a a

b b

Monitoring and Adjusting TherapyBest Practices for Family Physicians

• Ms. Johnson starts pharmacologic therapy and is considering CBT but wants to discuss it with her husband– How often should she be seen for pharmacotherapy visits?– How will you evaluate effectiveness?– How will you evaluate safety and side effect burden?– At what point would you change therapy because of lack of response?– What is the minimum level of improvement that is acceptable?

Patient Case: Monitoring and Managing Therapy

• MBC consists of several simple components: – Accurately assessing symptom severity– Ensuring adequate antidepressant dosage– Assessing medication tolerability– Monitoring and promoting treatment adherence– Ensuring treatment safety

• Treatment can be monitored quickly and easily with empirically validated assessment tools

• MBC has been shown to improve outcomes compared with usual treatment

Essentials of Measurement‐Based Care

Morris DW, et al. Curr Psychiatry Rep. 2011;13:446‐58.

• Monitor depression severity closely with PHQ

• Make decisions at critical decision points

• Use an evidence‐based treatment algorithm

• Manage aggressively during the acute phase and treat to remission

• Continue to monitor during continuation and maintenance phases

Implementing Measurement‐Based Care

• Broadly representative sample of adult outpatients with MDD (N = 3,671)• Employed ≥ 1 acute treatment step(s) in succession, aimed at achieving remission (defined as QIDS‐SR16 ≤ 5)

STAR*D Trial: Remission Rates Double With Stepwise, Algorithmic Treatment

Rush AJ, et al. Am J Psychiatry. 2006;163:1905‐17.

63%

44%

38%

33%

100%Estimated Cumulative Rate of Remission

37%

56%

62%

67%

Remaining in Depression

33%

38%

44%

63%

100%

“The present results serve to highlight the need for more effective short‐ and longer‐term treatments to bothachieve and sustain remission in more depressed patients sooner in the treatment sequence.”

3 months

• Monotherapy (SSRI)1

3 months

Switch to one of the following:• Monotherapy(3 options)

• Augmentation therapy(2 options)

• Augmentation with CBT

• CBT 2

3 months



3

3 months



4

Trea

tmen

t Steps

Limitations: May include open‐label design and self‐reported assessment of the QIDS‐SR16.

• Early improvement at 2 weeks predicts response– Lack of improvement in the first 2 weeks of treatment may indicate the need to

consider changes in management

Limitations: Included primarily patients with acute MDD; results may not apply to chronic or complicated depression.

Do We Reassess Too Late?

Szegedi A, et al. J Clin Psychiatry. 2009;70:344‐53.

53%

Early Improvement at Week 2 (n = 4,284)(≥ 20% reduction in HDRS17 scores)

89%

No Improvement at Week 2 (n = 2,263)

Went on to have a stable response at 4‐8 weeksDid NOT go on to have a stable response at 4‐8 weeks

2.98

‐4.82

‐9.31

‐4.17

1.71

‐10.05

‐13.4

‐8.59

‐16‐14‐12‐10‐8‐6‐4‐2024

Mild/Moderate Severe Very Severe All

Treatment as usualAlgorithm‐guided treatment

Care That Is Metrics‐Based, Algorithmic‐Guided—And Better

Trivedi MH, et al. Arch Gen Psychiatry. 2004;61:669‐80.

Chan

ge in

IDS‐C 3

0Total Score

Change in IDS‐C30 Scores From Baseline to 1 Year With Algorithm‐Guided Treatment vs Treatment as Usual, Categorized by Depression Severity

Limitations: Lack of randomization in this matched‐clinic, prospective, observational study.

P = .60 P = .01 P = .09 P = .002

• Do more than measure—incorporate outcomes into the clinical encounter

• Use patient‐reported outcomes—they are more accurate than clinician‐reported outcomes

• Collect metrics frequently to gauge clinical state• Use measures that closely correlate to depression• Use instruments that are reliable and sensitive to change• Use methods that are low cost and easy to implement

Making Metrics Work

Dissemination of Integrated Care Within Adult Primary Care Settings: The Collaborative Care Model. APA/APM Report. 2016;11.

• Misdiagnosis (e.g., bipolar disorder)• Depression severity and chronicity• Specific depressive subtypes

– Psychotic depression, atypical depression, melancholic features• Psychiatric comorbidities

– Anxiety disorders, panic disorder, personality disorder• Medical comorbidities

– Cardiovascular disease, chronic pain• Age at onset < 18 years• Substance abuse• Pharmacokinetics, pharmacogenetics• Patient nonadherence to treatment

Factors Associated With Treatment Resistance

Gaynes B. J Clin Psychiatry. 2009;70:10‐5.

• In an observational study (N = 147) of patients taking antidepressant therapy for any condition:

Patient Medication Nonadherence May Be Underappreciated by Physicians

Hunot VM, et al. Prim Care Companion J Clin Psychiatry. 2007;9:91‐9.

19%50%

Only 19% took their medications according to clinical guidelines during the 6‐month

dosing period

50% of patients discontinued

treatment altogether

89% did not inform their doctor

Of those whostopped prematurely:

• Primary care physician communication associated with adherence– How to take the medication (e.g., daily)– Short‐term, long‐term expected effects of the medicationMay take 2‐4 weeks to see effect

– Medication must be continued even when patient is feeling better– Patient must not stop the medication without calling first– Instructions on resolving questions and concerns– How the medication is thought to work– Antidepressants are not “addictive”

Increasing Adherence for Antidepressants

Brown C, et al. Med Care. 2005;43:1203‐7; Lin EH, et al. Med Care. 1995;33:67‐74.

Conclusions

• Remission and functional recovery are the goals • Metrics point the way to response, remission• Most efficacious/safest treatments first• Both pharmacologic and nonpharmacologic approaches work, but severe symptoms typically require pharmacologic treatment

• Subsequent interventions tend toward increased complexity and increased risk

• Patient presentation determines entry point• Patient preferences are important for adherence, efficacy

Principles of MDD Treatment

• MDD is underdiagnosed and often untreated or undertreated in the US

• Metrics can assist in the recognition and management of patients with MDD

• Treatment to remission is the goal

• Achieving and maintaining remission often require repeated trials of robust interventions (pharmacologic and nonpharmacologic), which are sustained over time

Key Takeaways

Documents

Sponsorship and Supportdepression in clinical practice. •Recognize the relationship between depression and cognitive ... •No 2 people will have the exact same signs and symptoms