From Depression to Wellness in MDD

Paul P. Doghramji, MD, FAAFP

Family Practice Physician

Collegeville Family Practice & Pottstown Medical Specialists, Inc.

Medical Director of Health Services, Ursinus College – Collegeville, PA

Attending Family Practice Physician, Pottstown Memorial Medical Center – Pottstown, PA

Learning Objectives

▪ Improve diagnosis of MDD

▪ Implement patient centered treatment approaches to

promote physical, emotional and cognitive wellness

▪ Change practice systems to improve diagnosis,

achieve remission, and return patients to complete

wellness

UNDER-treatment is common

▪ 6.7% of patients meet criteria for 12-month diagnosis of MDD

▪ 74% recognize need for treatment

▪ Of the 77% who receive treatment,

▪ 46% receive minimally adequate treatment

▪ RESULT − only 1 in 4 patients meeting criteria for diagnosis of MDD

receive adequate treatment

Thornicroft G et al. Br J Psych 2016. bjp.bp.116.188078.

Treatment Goals in Depression

1. Full remission

▪ 2-month period devoid of signs and symptoms*

▪ Lowers risk of relapse

2. Maintain recovery

3. Return to wellness

*APA 2013; DSM 5th Edition

Early Individualized TreatmentReview of 30 studies

▪ Increases likelihood of full

symptomatic and functional

recovery

▪ Allows early decisions that

optimize treatment rapidly

Habert et al. Prim Care Companion CNS Disord. 2016:18(5):10.4088/PCC.15m01926.

Meet Amanda

Annual visit

▪ 45 yo married female

▪ Hasn’t felt herself for >2 months

▪ Low energy

▪ Reduced appetite

▪ No interest in sex

▪ Husband feels she is withdrawn

▪ Insomnia - uses diphenhydramine

Practical Treatment of MDD

▪ Assess

▪ Evaluate patient safety - suicidal

▪ Address functional impairments and QOL

▪ Provide education

▪ Coordinate care

▪ Monitor status

▪ Enhance treatment adherence

APA: Practice guideline for Treatment of patients with MDD, 3rd edition 2010.

Detect and Diagnose

Have system in place to

determine if patient is

depressed

1. Screening

questionnaires

(PHQ-2 and PHQ-9)

2. DSM-5 Criteria

Maurer DM. 2012 Am Fam Phy 85(2):139-144.

For ≥ 2 weeks:

5 or more symptoms →

▪ ≥ 1 symptom =

depressed mood or loss

of interest/pleasure

▪ Symptoms = change

from previous functioning

1. Depressed mood (subjective or observed); in children and adolescents,

mood can be irritable

2. Loss of interest or pleasure

3. Change in weight or appetite

4. Insomnia or hypersomnia

5. Psychomotor retardation or agitation (observed)

6. Loss of energy or fatigue

7. Feelings of worthlessness or guilt

8. Impaired concentration or indecisiveness

9. Thoughts of death or suicidal ideation or attempt

American Psychiatric Association; 2013 Diagnostic and statistical manual of mental disorders.5th ed. Arlington.

DSM-5 Criteria for MDD

Several days

More than half of days

Nearly every day

1. Little interest or pleasure in doing things 0 1 2 3

2. Feeling down, depressed, or hopeless 0 1 2 3

3. Trouble falling or staying asleep, or sleeping too much 0 1 2 3

4. Feeling tired or having little energy 0 1 2 3

5. Poor appetite or overeating 0 1 2 3

6. Feeling bad about yourself—or that you are a failure and that you have let yourself or your family down

0 1 2 3

7. Trouble concentrating on things, such as reading the newspaper or watching televisions

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

Add columns:

Total: 0

10. If you checked off any problems, how difficult has it been for you to do your work, take care of things at home, or get along with other people?

Not difficult at all

Somewhat difficult

Very difficult

Extremely difficult

PHQ-2

Patient Health QuestionnairePHQ-2 or PHQ-9

Interpreting PHQ-9

PHQ-9 Score

DSM-IV-TR Criterion

Symptoms Depression Severity Proposed Treatment Action

1-4 Few None None

5-9 5 Mild depressive symptoms Watchful waiting, repeat PHQ-9 at follow-up

10-14 5-6 Mild Major DepressionTreatment plan, considering counseling,

follow-up and/or pharmacotherapy

15-19 6-7 Moderately Major DepressionImmediate initiation of pharmacotherapy

and/or psychotherapy

20-27 7 Sever Major Depression

Immediate initiation of pharmacotherapy

and, if severe impairment or poor response

to therapy, expedited referral to a mental

health specialist for psychotherapy and/or

collaborative management

Back to Amanda

▪ PHQ-9 Score = 11

▪ DSM-5 Criteria = 5

▪ Rule out

▪ Bipolar disorder

▪ Medication induced

Meds That May Cause Depressive Symptoms

Neurologic Oncologic Cardiovascular

Barbiturates Vincristine β-Blockers (controversial)

Anticonvulsants Vinblastine Clonidine

Levodopa Pemetrexed Methyldopa

Amantadine L-Asparaginase Reserpine

Flunarizine Paclitaxel Hydralazine

Docetaxel Amiodarone

Interleukin-2 Digoxin

Corticosteroids

Tyrosine kinase inhibitors

Anti-infective agents Other agents Substances

Efavirenz Isotretinoin Marijuana

Zidovudine GnRH agonists Alcohol

Interferon-α Clomiphene Others

MefloquineOral and depot contraceptives

(controversial)

Amphotericin B

Celano CM, et al. Dialogues Clin Neurosci. 2011;13:109-125.

Path to ‘WELLNESS’

Jain S. Mental Wellness Matters: Applying Wellness Interventions Even in the Busiest Clinical Practice; US Psych Mental Health Congress.

Assessing Patient Wellness

Where is your patient and where do they want to be?

▪ Physical

▪ Emotional

▪ Social

▪ Cognitive

Tools for Achieving Wellness

▪ Nutrition

▪ Sleep

▪ Exercise

▪ Social connectedness

▪ Mindfulness

▪ Cognitive functioning

Wellness Interventions Improve Outcomes

Intervention

▪ Exercise: walk >5 days/week

▪ Sleep hygiene

▪ Nutrition: log meals, snacks,

alcohol

▪ Mindfulness meditation daily

▪ Social connectedness practice

Results

▪ PHQ-9 improved: 8.9 to 5

▪ Anxiety-GAD improved: 7.9 to 4.3

▪ WHO-5 Wellness: 10.7 to 15.4

▪ Other improvements

▪ Social connectedness

▪ Emotional eating

▪ Mindful awareness

▪ Sleep quality

Wellness through Physical Activity

Moderate exercise and physical activity reduces

depressive symptoms

▪ Walking, dancing, swimming, gardening, etc.

▪ 150-300 minutes/week

▪ 10-60 minute intervals - need not be done in one setting

▪ Monitor

Catalan-Matamoros D et al. Exercise Improves Depressive Symptoms in Older Adults. 2016 Psych Res 244:202-9.

Wellness through Healthy Diet

Healthy diet promotes overall health

Appropriate calorie level

▪ 1600-2400 calories/day for women

▪ 2000-3000 calories/day for men

Healthy eating pattern on most days

▪ Dash diet

▪ Mediterranean diet

http://health.gov/dietaryguidelines/2015/guidelines/

Wellness through Sleep Hygiene

7-9 hours of sleep reduces depression

and disease risk

▪ Avoid caffeine and rich foods near bedtime

▪ Alcohol in moderation

▪ Establish a bedtime routine

▪ Create a pleasant sleep environment of 60-67 degrees

sleepfoundation.org/sleep-topics/sleep-hygiene

Wellness through Mindfulness

Mindfulness: Fully present and aware of where

we are and what we are doing - not over reacting

to what is going on around us

▪ Practice daily

▪ Set aside a time and space to relax and focus

▪ Be physically attentive to the present moment

▪ Dispel judgmental thoughts

▪ Return to the present as it is

https://www.psychologytoday.com/blog/the-courage-be-present/201001/how-practice-mindfulness-meditation

Wellness through Social Connectedness

How a person interacts with community,

friends, and family.

▪ Micro socialization

▪ Daily, small opportunities to say hello, smile

▪ Micro socialization add up to feel better

▪ Macro socialization

▪ Getting together with close friends and family members to have fun, and have deep,

meaningful conversations

Cognitive Behavioral Therapy (CBT)is Effective

Negative, dysfunctional thinking affects mood, sense of self,

behavior, and physical state.

CBT based on 2 tasks:

1. Cognitive restructuring to change

thinking patterns

2. Behavioral activation - learning to

engage in enjoyable activities and

develop problem-solving skills

Twomey C, O’Reilly G, Byrne M. 2014 Fam Prac 32(1):3-15.

CBT: Who is likely to benefit?

Patient’s take active role in learning/monitoring negative thoughts for 14-16 weeks

▪ Motivated

▪ Sees self as able to control events that happen

▪ Capacity for introspection

Online sessions validated as successful:

▪ www.learntolive.com

▪ www.moodgym.anu.edu.au/welcome

Wellness Recommendation for Amanda

▪ Medication?

▪ CBT?

▪ Wellness modifications?

▪ Follow up

Meet Sam

▪ 36 year old Male

▪ Return visit: 12 weeks since Dx

▪ Treated with SSRI

▪ Feels better

▪ Annoyed by problems with concentration,

especially with work projects that require

immediate attention and problem-solving

▪ Feels others think he is ‘not pulling his weight’

▪ Relationship with his wife has improved,

but sexual performance is still ‘off’ for Sam

▪ Repeated PHQ-9 score is 10

Selecting an Anti-DepressantFactors to Consider

Patient Factors

▪ Clinical features and dimensions

▪ Comorbid conditions

▪ Response and side effects during

previous use of antidepressants

▪ Patient Preference

Medication Factors

▪ Efficacy - generally comparable

▪ Comparative tolerability (AEs)

▪ Interactions with other meds

▪ Simplicity of use

▪ Cost and availability

Kennedy SH, et al. Can J Psych 2016:61(9):540-560.

Patient Treatment Preference Predicts Treatment Outcome

45.5

7.7

27.6

39.3

22.2

50.0

28.0

17.6

45.5

39.8 39.1

52.2

0

20

40

60

Medication Psychotherapy Combination None

Per

cen

t R

emis

sio

n

Preferred Treatment

Medication Psychotherapy Combination

Kocsis JH et al. J Clin Psychiatry. 2009;70(3):354-361.

Pharmacotherapy in MDD

▪ Choose an initial medication and starting dose

▪ If side effects occur

▪ Lower dose

▪ Change to a different med

▪ Evaluate response allowing sufficient duration

▪ Titrate dose up

▪ Combine medications

Evolution of Depression Meds

Symptom Reduction

Response

Remission

Improved Function

Functional Remission

Improved QOL

Cognitive Remission

McIntyre RS J Clin Psychiatry. 2013;74:14-18.

>1990

2000

2010

2014

Pharmacologic Classes for DepressionClass Examples Side Effects

SSRI

fluoxetine (1987), sertraline (1991),

paroxetine (1992), fluvoxamine (1994),

citalopram (1998), escitalopram (2002)

GI, activation, insomnia, sexual dysfunction, migraines, falls, weight gain,

potential for serotonin syndrome discontinuation syndrome

SNRI

venlafaxine (1993), desvenlafaxine

(2008), duloxetine (2004),

levomilnacipran (2013)

GI, activation, sexual dysfunction, increased pulse rate, dry mouth, excessive

sweating, increased blood pressure, potential for serotonin syndrome,

discontinuation symptoms

TCA

amitriptyline (1961), nortriptyline

(1964), imipramine (1959),

desipramine (2014), doxepin (2010)

Cardiovascular effects, arrhythmias, orthostatic hypotension, dry mouth, sexual

dysfunction, tachycardia, impaired vision, memory and concentration

impairments, sedation, weight gain, myoclonus

MAOI

phenelzine (1961), tranylcypromine

(1960), isocarboxazid (1999),

selegiline (2006)

Hypertensive crisis, potential for serotonin syndrome, orthostatic hypotension,

weight gain, sexual dysfunction, headaches, insomnia

Others

bupropion (1985), nefazodone (1996),

trazodone (1981), mirtazapine (1996),

agomelatine

Nausea, headaches, dizziness, insomnia, somnolence, tremors, seizures, dry

mouth sedation, weight gain

Multimodal

AntidepressantsVilazodone (2011), vortioxetine (2013) Nausea, diarrhea

APA: Practice guideline for the treatment of patients with major depressive disorder. 2010.;Taylor et al. Maudaley Prescribing Guidelines, 10th ed. 2009.

Institute for Clinical Systems Improvement; Depression in Primary Care 2016. 1-57.Frampton, JE. Vortioxetine; A Review in Cognitive Dysfunction in Depression 2016 Drugs 76:1675-1682.

EMA Summary of Product Characteristics for Valdoxan (agomelatine) 2009.PI Forest Labs. Vilazodone hydorchloride 2012. Updated 2014.

Recommendations Based on Primary Symptoms

Symptoms Recommendation Comments

AnxietyAll the anti-depressants are generally

equally effective

Research suggests no significant differences between SSRIs,

SNRIs, or bupropion

Sadness, gloomyAll the anti-depressants are generally

equally effective

Research suggests no significant differences between SSRIs,

SNRIs, or bupropion

Cognitive dysfunction

Vortioxetine

Bupropion

Duloxetine

SSRIs

Early research suggests some newer meds may have effects on

improved cognition (such as attention, concentration, memory,

organizing, etc.)

Insomnia

Melatonin

Mirtazapine

Trazodone

Beneficial effects on helping sleep need to balance daytime

sleepiness

Physical symptoms, pain,

fatigue

SNRIs

Bupropion

Certain anti-depressants may be better than others in

addressing pain

Kennedy SH, et al. CANMET Guidelines 2016; Qaseem A et al. ACP Clinical Guidelines 2008.

Does Sam have Cognitive Impairment?

▪ 36 year old Male

▪ Return visit: 12 weeks since Dx

▪ Treated with SSRI

▪ Feels better

▪ Annoyed by problems with concentration,

especially with work projects that require

immediate attention and problem-solving

▪ Feels that others think he is ‘not pulling

his weight’

▪ Relationship with his wife has improved, but

sexual performance is still ‘off’ for Sam

▪ Repeat PHQ-9 score = 10

Cognitive Impairment in MDD

▪ Prevalence in adults with MDD:

▪ Among all: 30% - 40%1

▪ Among >65 years old: 50% - 70%1

▪ Impact QOL and functional outcomes

▪ Cognitive symptoms can remain after

remission2

▪ 1 in 3 patients responding to therapy

report residual cognitive symptoms3

1. Gualtieri CT, Morgan DW J Clin Psych 2008;69:1122-1130. 2. Conradi JH, et al Psychol Med 2001;41:1165-1174. 3. Fava et al, J Clin Psychiatry 2006;67:1754.

4. McIntyre RS et al. Depress Anxiety 2013;30:515-527.

Impaired cognition is strongly associated

with high rate of relapse and

recurrence4!!

Key Domains of Cognitive Function in MDD

Attention Domain Ability to focus on several objects/trains of thought

Real-life-manifestation Difficulty with concentrating, focus, attention

Memory Domain Visual and verbal memory, time/places, meaning of things

Real-life-manifestation Forgetfulness, word-finding difficulty

Executive Function DomainInhibition, working memory, verbal fluency, planning,

problem solving

Real-life-manifestation Indecisive in prioritizing, multitasking, decisions, planning

Psychomotor Domain Time to perform motor actions from mental activity

Real-life-manifestation Slow processing and responding

Screening for Cognitive Function

▪ Ask patient questions from

4 Domains

▪ Use tools like Perceived Deficit

Questionnaire PDQ-5

▪ Measures self-reported

cognitive impairment

“Traditional” Antidepressant Studies: Effects on Cognition

▪ Improvements in cognition secondary to improvements in

mood symptoms

▪ Conventional antidepressants have not shown significant

improvements in cognitive symptoms

▪ Some antidepressants worsen cognitive deficits

McIntyre RS, et al. Depress Anxiety. 2013;30:515-527; Fava M, et al. J Clin Psychiatry. 2006;67:1754-1759; Greer TL, et al. CNS Drugs. 2010;24:267-284; Herrera-Guzman I. J Affect Disord. 2010;123:341-350; McClintock SM, et al. J Clin Psychopharmacol. 2011;31:180-186; Trivedi MH, Daly EJ. Dialogues Clin Neurosci. 2008;10:377-384; Millan MJ, et al. Nat Rev Drug Discov. 2012;11:141-168.

New Multimodels -Responsible for Diverse Effects?

▪ Vortioxetine

▪ Combined effects on 5-HT

receptors and serotonin

transporter

▪ Acts as serotonin reuptake

inhibitor

▪ 5-HT1A agonist

▪ 5HT3

▪ 5HT7 antagonist

▪ 5-HT1B receptor partial agonism

▪ Serotonin transporter inhibition

▪ Full mechanism remains unclear

▪ Vilazodone

▪ Combines inhibition of serotonin

reuptake and partial agonism of

5-HT1A

▪ Full mechanism remains unclear

Lam RW, Kennedy SH, McIntyre RS, Khullar A. Cognitive Dysfunction in Major Depressive Dsorder: Effects on Psychosocial Functioning and Implications for

Treatment. 2014 Psychiatry 59(12):649-654. Katona CL, Katona CP. New generation multi-model antidepressants: focus on vortioxetine for MDD. 2014

Neuropsych Dis Treat 10:349-354. Richelson E. Multi-modality: a new approach for the treatment of MDD 2013 Int J Neuropsychopharmacol 16(6): 1433-1442.

Pharmacologic Effects on Cognitive Function in Young Adults with MDD

Learning &

Memory

Attention/

Concentration

Executive

Function

Processing

Speed

Vortioxetine 1 1 1 1

Duloxetine 1

Lisdexamfetamine 2

Other(SSRIs,

SNRIs, buproprion)

3 3 3 3

Modafinil 3 3 3 3

Erythropoietin 2 2 2 2

Level 1: Replicated placebo-controlled trial evidence with demonstration of independent effect

Level 2: Single placebo-controlled trial evidence with demonstration of independent effect

Level 3: Uncontrolled evidence with lack of demonstration of independent effect

McIntyre RS et al. CNS Drugs 2015:29:577-589.

Cognitive Effects of Antidepressants in MDD

McIntyre RS et al. Effects of Vortioxetine on Cognitive Function in Patient with MDD:

A Meta-Analysis of Three Randomized Controlled Trials. 2016 Intl Journ of Neuropsychopharmaco 19(1):1-9.

Meta-Analysis

▪ 3 Randomized, DB, PC

8 week trials of vortioxetine

▪ 2 duloxetine-referenced

trials

▪ Vortioxetine consistently

improved cognition function

independent of depressive

symptoms

Change in DSST from baseline to 8 weeks after adjustment in change in MADRS total score.

Switch or Add Medication?

Consider ‘switching’

▪ It is the first antidepressant trial

▪ Poorly tolerated side effects

▪ Lack of response (<25%

improvement)

▪ More time to wait for patient

response - less severe, less

functional impairment

▪ Patient prefers to switch

Consider combining med

▪ 2 or more antidepressant trials

▪ Initial antidepressant well

tolerated

▪ Partial response to (>25%

improvement) initial antidep.

▪ Specific residual symptoms and

SEs can be targeted

▪ Less time to wait for response

▪ Patient prefers adding medication

Kennedy SH, et al. Can J Psychiatry. 2016;61(9):540-560.

Adherence in MDD: <40% Patients adhere to initial therapy1

▪ Educate

▪ Length of therapy

▪ Alternative medication options

▪ Side effect monitoring/management

▪ Consequences of unsuccessful

treatment

▪ Follow up q 2 weeks

▪ Communicate frequently

▪ Apps and reminders to engage patients

▪ Encourage wellness activities

1. Offson M. et al. Am J Psych 2006;163:101-108.

Patient Satisfaction Key to Psychiatry Adherence

2017 Meta analysis

▪ 20%-75% of patients receiving psychosocial

mental health services “drop out”

▪ 60% on anti-depressants are not taking by

6 months

The Patient-Provider Relationship

was key:

Patients want..

1. Quality information

2. Sharing in decision-making

3. Continuity of care

Patient Satisfaction Key to Psychiatry Adherence ‘Crisis’.

Medscape Apr 05,2017 Abstract at EPA 2017 Congress

Shared Decision Making in MDD Improves patient participation, adherence, and clinical outcomes

▪ Uses educational aids

▪ Incorporates patient values,

priorities, concerns, goals

▪ Reviews risk and benefits of

treatment options (O’Connor, 2007)

Wellness Recommendation for Sam

▪ Medication(s)?

▪ CBT?

▪ Wellness?

▪ Follow up?

▪ Continuity of care?

Follow-up and Monitoring to Achieve Outcomes

Can we measure WELLNESS?

Tools:

▪ PHQ-9

▪ PDQ-5

▪ HERO

HERO: Measure Wellness

▪ During last 7 days

▪ How Happy?

▪ How Enthusiastic?

▪ How Resilient?

▪ How Optimistic?

▪ Rate mental wellness

▪ Not at all good to

Extremely good

Copyright 2017, Dr. Saundra Jain and Dr. Rakesh Jain.

Summary

▪ MDD can present in many subtle ways, and screening for it is imperative in symptoms suggestive of MDD

▪ Use PHQ-9 to screen for MDD, and assess severity, as well as follow progress

▪ Make full remission, then wellness your goal in treating MDD patients with appropriate treatment and continued lifestyle modification

▪ Address all 3 domains of depression, including mood, energy, and cognitive function