focusing on depression in the community - ipha 2016- final.pdf · dosing adverse effects clinical...

Focusing on Depression in the Community

Kelly N. Gable, Pharm.D., BCPPAssociate Professor SIUE School of Pharmacy

Disclosure and Conflict of Interest

Dr. Gable declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria.

Pharmacist Objectives

At the conclusion of this program, the pharmacist will be able to:1. Discuss depression screening tools and how to identify

depression. 2. Identify ways to incorporate depression screenings into

community pharmacy settings. 3. Review treatment guidelines and clinical

recommendations for the treatment of depression. 4. Discuss a plan for referral and treatment when depression

is identified.5. Describe patient cases that the pharmacist may encounter

in the community setting.

Pharmacy Technician Objectives

At the conclusion of this program, the pharmacy technician will be able to:

1. Recognize patients appropriate for referral to pharmacist for depression screening.

2. Describe classes of drugs used to treat depression.

3. List risk factors for suicide and steps to take in a suicide crisis.

Pre-Test Question 1

What depression screening tool is the most widely used and recommended in primary care treatment settings?

A. Beck Depression Inventory (BDI)

B. Hamilton Depression Rating Scale (HAM-D)

C. Patient Health Questionnaire (PHQ-9)

D. Geriatric Depression Scale (GDS)

Pre-Test Question 2

Which of the following medications is recommended as a first-line treatment for a first episode of depression?

A. Lithium

B. Bupropion

C. Doxepin

D. Aripiprazole

Pre-Test Question 3

Which of the following is considered a protective factor against suicide completion?

A. Older age

B. Experiencing psychosis

C. Bereavement

D. Religion

Types of Mood Disorders

• Cyclothymic Disorder

• Bipolar I Disorder

• Bipolar II Disorder

• Schizoaffective Disorder

• Persistent Depressive Disorder (Dysthymia)

• Disruptive Mood Dysregulation Disorder

• Premenstrual Dysphoric Disorder

• Major Depressive Disorder – Specifiers: with catatonic features, melancholic features, atypical

features, psychotic features, anxious distress, seasonal pattern, postpartum onset

Derived from DSM-5 Diagnostic Criteria

Assessing for Depression- SIGECAPS

Depressed Mood

Sleep Changes

Interest Lacking

Guilt

Hopeless-ness

Energy Decrease

Poor Focus

Appetite Changes

Tearfulness

Irritability

Excessive Worry

Chronic Pain

Headaches

Social Isolation

Medical Causes of Depression

Medications Medical Conditions

Cardiovascular Agents: methyldopa, reserpine, clonidine, beta-blockers (propranolol)

• Cardiovascular disease (stroke, CHF)

• Endocrine disorders (hypothyroidism, diabetes)

• Autoimmune conditions (Lupus, MS)

• Chronic pain conditions

• Infectious diseases (HIV, Syphilis)

• Oncology/hematology (cancer, anemia)

• Neurological conditions (Parkinson’s disease, dementia)

Sedative-hypnotics: alcohol, benzodiazepines, barbiturates, chloral hydrate

Hormones: corticosteroids, progesterone, estrogen withdrawal, anabolic steroids

Others: interferon, isotretinoin, varenicline, withdrawal from stimulants (cocaine, methamphetamine)

Depression is 2X as likely in patients with heart disease & diabetes

Major Depressive Disorder

A. Period of at least 2 weeks in which patient exhibits 1) depressed mood &/or 2) anhedonia

B. ≥ 5 out of 9 symptoms: – Changes in weight (~5% over 1 month), sleep (insomnia vs

hypersomnia), psychomotor agitation or retardation, loss of energy (small tasks- getting out of bed), feelings of worthlessness/guilt, difficulty concentrating & making decisions, suicidal ideation

C. Never been a manic or hypomanic episode

D. Must impair social or occupational areas of functioning

E. Not due to substance abuse or general medical conditions

Derived from DSM-5 Diagnostic Criteria

Major Depressive Disorder

• Females > males (MDD 2:1)

• Lifetime prevalence: 10 – 25% (female); 5 – 12% (male)

• Onset ~ mid to late-20s, develops over days to weeks

• Chances of relapse: – 1 episode: 50 – 60% will have 2nd episode

– 2 episodes: 70% will have a 3rd episode

– 3 episodes: 90% will have a 4th episode

• Episodes often follow severe psychosocial stressors

• Depression is among the leading causes of disability in persons ≥ 15 years and is common in patients seeking care in the primary care setting.

Depression Screening

• Patient Health Questionnaire-2 – 2 screening questions – Used in primary care settings

• Patient Health Questionnaire-9– 9 screening questions – Assessing for depression– Scores >15 likely MDD but

needs to accompany full clinical interview

– Hospital Anxiety & Depression Scales – Geriatric Depression Scale – Edinburgh Postnatal Depression Scale

(EPDS)

Depression Screening

• Screening for depression in the general adult population (regardless of risk factors) should occur (including pregnant and postpartum women).

• Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.

Screening for Depression in Adults: US Preventive

Services Task Force Recommendation Statement

Depression Screening: Risk/Benefits

• Benefits of Early Detection/Treatment: – Reduction or remission of depression symptoms

– Decreased clinical morbidity

– Improved clinical outcomes in pregnant and postpartum women

• Harms of Early Detection/Treatment: – The magnitude of harm from screening for depression

in adults is small to none

– The magnitude of harm from treatment with CBT in postpartum and pregnant women is small to none

– Antidepressants associated with a low riskScreening for Depression in Adults: US Preventive

Services Task Force Recommendation Statement

Depression Screening: at the Pharmacy

• Screenings are NOT diagnostic tools; however they DO improve clinical outcomes

• Pharmacists as part of a multidisciplinary team within primary care are encouraged to initiate screenings

• Unknowns:

– Frequency? -yearly is common

– Will screening lead to more people receiving treatment?

– How to overcome barriers to establishing adequate access to care?

First Episode Depression

• Kathy is a 32 year-old female patient presenting for her annual primary care appointment.

• During routine questioning, she reports a more recent decline in her overall mood x 2 months.

• She describes chronic insomnia, low energy, and poor focus when completing work projects.

• She reports a recent 10 pound weight loss due to minimal appetite. This is her first depressive episode.

• Current Medications: ethinyl estradiol, lisinopril

What treatment would you recommend for Kathy?

A. Bupropion

B. Nortriptyline

C. Vilazodone

D. Sertraline


Selection of Initial Antidepressant

1. Patient preference 2. History of prior response3. Family history of response to medication 4. Safety in overdose5. Chronicity of the disorder 6. Adverse effect profile7. Patient age8. Concurrent medical illness (HTN, seizure disorder)9. Concurrent medications (drug interactions)10.Adherence (dosing schedule)11.Cost

Antidepressant

Choices

Bupropion

SNRIs

SSRIsTCAs

Mirtazapine


Selective Serotonin Re-Uptake Inhibitors (SSRIs): Dosing & Clinical Pearls

Dosing *Adverse Effects Clinical Pearls

Fluoxetine (Prozac®) 20 – 80 mg/day

Insomnia, activation Prozac® Weekly, Sarafem®

Good alternative for nonadherence (t ½ ~7 days)

Paroxetine (Paxil®) 10 – 60 mg/day

Constipation, dry mouth, sedation

Shortest t ½ (< 24 hours) & high serotonin withdrawal Most well-studied for anxiety disorders

Sertraline (Zoloft®) 50 – 200 mg/day

Nausea, diarrhea Food enhances bioavailability by 40%Less CYP450 drug interactions

Fluvoxamine (Luvox®) 50 – 300 mg/day

Sedation More CYP450 drug interactions Only FDA-indicated for OCD

Citalopram (Celexa®) 20 – 40 mg/day

Dose-dependent QTcprolongation

FDA notification 2011: should no longer be used at doses > 40 mg/day due to QTcprolongation

Escitalopram (Lexapro®) 10 – 20 mg/day

Generally well-tolerated

Less CYP450 drug interactions 10 mg Lexapro® = 20 mg Celexa®

*All SSRIs can cause nausea, headache, sexual dysfunction.


• Kathy is initiated on sertraline 50 mg daily.

• 4 weeks into treatment, she reports ~50% improvement in her mood.

• She continues to describe insomnia.

Course of Treatment in Depression

Kupfer DJ. Long-term treatment of depression.

J Clin Psychiatry. 1991;52(suppl 5):28–34.

Insomnia and Depression

• Trazodone

– 25 – 50 mg q HS (for insomnia)

– 200 – 600 mg/day (for depression)

• Mechanism: blocks 5-HT re-uptake, post-synaptic 5-HT2A, histamine1

• Adverse Effects: sedation, orthostasis, priapism (rare)

– No anticholinergic side effects, safer in overdose

Complex Depression

• Jason is a 51 year-old male patient presenting for an MTM session at the pharmacy.

• He is diagnosed with diabetes, neuropathy, hypertension, and HIV.

• He reports chronic neuropathic pain, depressed mood, anhedonia, and vacillating suicidal thoughts.

• He smokes marijuana and cigarettes daily.

• Current medications: metformin, glyburide, hydrochlorothiazide, atenolol, efavirenz/emtricitabine/tenofovir (Atripla®)

Antidepressant

Choices

Bupropion

SNRIs

SSRIsTCAs

Mirtazapine


Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Dosing Adverse Effects Clinical Pearls

Venlafaxine(Effexor®)

150 – 225 (XR) or 375 (IR) mg/day

Nausea, headache, insomnia, sweating, sexual dysfunction

Tolerability worse with IR formulation ↑ diastolic blood pressure (dose-related > 225 mg/day; 9% at doses > 300 mg/day)

Desvenlafaxine(Pristiq®)

50 – 100 mg/day

Similar tolerability profile to venlafaxine

Active metabolite of venlafaxine Studied for vasomotor symptoms of menopause

Duloxetine(Cymbalta®)

40 – 60 mg/day

Nausea, insomnia, headache, sexual dysfunction, increase in blood pressure, sweating Mild anticholinergic: dry mouth, constipation, urinary retention

Often used for diabetic neuropathy & fibromyalgia BBW hepatotoxicity

Levomilnacipran(Fetzima®)

20 – 120 mg/day

Nausea, headache, sexual dysfunction, increase in blood pressure, sweating Mild anticholinergic: dry mouth, constipation, urinary retention

Newest SNRI- 2013Active enantiomer of milnacipran(Savella®)- approved for fibromyalgia Research shows no benefit over SSRIs or TCAs

Bupropion (Wellbutrin®)

• Bupropion IR 75, 100 mg (max 450 mg/day)

• Bupropion SR 100, 150, 200 mg (max 400 mg/day)

• Bupropion XL 150, 300 mg (max 450 mg/day)

– Dosage: 300-450 mg divided BID- no later than 4 pm

– Mechanism: inhibits DA & NE (minimal) reuptake

– Adverse Effects: headache, insomnia, nausea, agitation, seizure, weight loss (NO sexual dysfunction)

– Contraindications: alcohol abuse, seizure disorder, active eating disorder

Mirtazapine (Remeron®)

• Dosage: 15 – 45 mg/day• Mechanism: inhibits presynaptic alpha2

receptors increasing 5-HT & NE release; blocks postsynaptic 5-HT2/3 & H1 receptors

• Adverse Effects: – Sedation (less at 30 – 45 mg/day), ↑ appetite,

weight gain, dizziness – NO sexual dysfunction – May increase cholesterol (triglycerides)

• Comes in an ODT

Question from a Local Physician

I heard there is a new antidepressant on the market. How is it different from an SSRI or an SNRI?

Newer Antidepressants

• Vilazodone (Viibryd®)– Dosage: 10 – 40 mg/day with food – Mechanism: selective 5-HT re-uptake inhibitor & 5-

HT1A partial agonist – Adverse Effects: nausea, diarrhea, insomnia, headache – Minimal to NO sexual dysfunction

• Vortioxetine (Brintellix®) – Dosage: 10 mg initially; 20 mg goal dose – Mechanism: 5-HT reuptake inhibitor, 5-HT3

antagonist, 5-HT1a agonist – Adverse Effects: GI upset (nausea, diarrhea), sexual

dysfunction

Depression with Medical Complications….

• 58 y.o. male with hypertension, depression, hyperlipidemia, chronic back pain, DVT history

• Current medications include: – Ibuprofen 800 mg TID

– Atorvastatin 40 mg q HS

– Warfarin 5 mg q day

– Lisinopril 40 mg q day

– HCTZ 25 mg q day

– Diltiazem 180 mg q day

– Citalopram 60 mg q day

– Zolpidem 10 mg q day

• What concerns do you have with his treatment?

QTc Prolongation

• Causes: citalopram – dose dependent; TCAs

– 20 mg = 8.5 msec

• Preferred dose for hepatic impairment, > 60 y.o., taking other agents known to prolong QTc interval

– 40 mg = 12.6 msec (max dose)

– 60 mg = 18.5 msec

• Symptoms: fluttering feelings in chest, fainting

• Management: baseline ECG in those with pre-existing cardiovascular disease (CHF), monitor for hypokalemia & hypomagnesemia BEFORE initiating treatment

Antiplatelet Effect

• Causes: SSRIs/SNRIs/TCAs/vilazodone

• Symptoms: increased bruising and bleeding (↓ platelet aggregation)

• Management: cautiously prescribe NSAIDs, anticoagulation therapy, & SSRIs concomitantly

• **Warfarin is metabolized by CYP1A2, CYP2C, & CYP3A4 (avoid SSRI CYP450 inhibitors)

The provider decides to completely discontinue the citalopram due to cardiovascular and antithrombotic risk. Four days later the patient calls the pharmacy reporting severe anxiety, insomnia, and irritability.

What is this patient experiencing?

A. Serotonin Syndrome

B. Serotonin Withdrawal

C. Panic Attack

D. Myocardial Infarction

Depression with Medical Complications….

Serotonin Withdrawal

• Causes: abrupt discontinuation of antidepressant therapy (SSRI/SNRIs/TCAs/vilazodone)

• Symptoms: anxiety, agitation, irritability, sleep disturbances, dizziness, nausea, electric-shock like sensation on extremities or head (paresthesias)

– Usually occurs 1-3 days after d/c; lasts up to 2 weeks

– Worse with short ½ antidepressants such as paroxetine, fluvoxamine, & venlafaxine

• Management: re-start antidepressant and taper slowly @ 5 – 7 day intervals (except fluoxetine)

Phone Call to the Pharmacist

I need a recommendation for an antidepressant for my patient. They have been taking citalopram 20 mg x 2 years, initial effectiveness, however now complains of symptom relapse.

Time Course of Response

Start

Treatment

1 – 2 WEEKS

↑ Energy

Improved sleep

Improved appetite

3 – 4 WEEKS

Improved mood & less anhedonia,

↓ hopelessness/helplessness,

↓ suicidal ideation

Self care, concentration & memory

4 – 8 WEEKS

Relief of depressed mood

Adequate trial at adequate dosage

Poor Antidepressant Response

• ~2/3 of individuals fail to receive remission with initial antidepressant treatment

• Addressing reasons for poor treatment response:

Co-occurring substance use

Incorrect diagnosis (bipolar disorder)

Inadequate dose or duration of treatment

Nonadherence

Pharmacokinetic factors (CYP450 interactions)

Psychosocial stressors

Co-occurring medical condition (hypothyroidism)

Switching Antidepressants

• When to switch therapy? 4 to 8 weeks at adequate dose with no or <50%

response rate

• What to switch to? SSRI, SNRI, bupropion, mirtazapine (one that has not

already been tried)

No studies provide guidance on which antidepressant to choose

• How to switch? Cross-titration / taper vs equivalent dose conversion

Antidepressant Augmentation

• Treatment Resistance: failed to respond to 2 separate trials of different antidepressants (adequate dose/duration)

• Consider psychotherapy

• Augmentation strategies: – L-triiodothyronine (T3) 20 - 25 mcg/day

– Lithium: 600 – 900 mg/day

– Buspirone: 30 – 60 mg /day (divided)

– Folate: 400 mcg/day

– L-methylfolate: 7.5 – 15 mg/day

– Aripiprazole: 2 – 15 mg/day

– Brexpiprazole: 1 – 3 mg/day

– Quetiapine XR: 50 – 150 mg/day

– Olanzapine 5 – 15 mg/day

– Electroconvulsive Therapy (ECT)

Suicide & Antidepressants

• October 15, 2004: Black Box Warning

• FDA required warning statement recommending close observation of young adult & pediatricpatients (< 24 y.o.) treated with antidepressants for worsening depression or the emergence of suicidality

• A Patient Medication Guide must accompany all antidepressant prescriptions

• This is an opportunity for screening and education

Suicidality Definitions

• Suicide ideation: thoughts of engaging in behavior intended to end one’s life

• Suicide plan: the formulation of a specific method through which one intends to die

• Suicide attempt: engagement in potentially self-injurious behavior in which there is at least some intent to die

• Nonsuicidal self-injury (e.g., self-cutting): self-injury in which a person has no intent to die

Suicide Risk/Protective Factors

Risk Factors Protective Factors

• Prior attempts • Family history of suicide • Psychosis • Drug/alcohol abuse • A recent loss • Hopelessness • Chronic painful illness • Male gender (4:1) • Firearm availability • Elderly or adolescent

• Connectedness to family• Marriage and young children

in the home• Meaningful ways of coping

with stress• Awareness of

religious/moral/social opposition

• Involvement with a hobby or organization

• Positive worldview

How to Respond in Crisis Situations

• Take action. Remove means, such as guns or stockpiled pills.

• Get help from individuals or agencies specializing in crisis intervention and suicide prevention.

• SAMHSA Behavioral Health Treatment Services Locator:

– https://findtreatment.samhsa.gov/

• Call 911.

• Encourage the use of the National Suicide

Prevention Lifeline: 1-800-273-TALK

Referral and Follow-Up Planning

• Do NOT screen with out a proper referral system in place!

• Evaluate the behavioral health services in your area• Check antidepressant refill history and offer

psychoeducation when appropriate • When providing MTM, referrals to a psychiatric

specialist should be made when: 1. The patient has failed > 2 antidepressant trials 2. Psychotic symptoms are present 3. Suicidal thoughts are present 4. There is a history of trauma 5. Co-occurring substance use disorder

Antidepressant Counseling

60% of patients stop antidepressant treatment within 3 weeks of initiation……

1. Talk about the benefits of treatment

2. Antidepressant effects are delayed; they may take up to 4 to 8 weeks to be effective.

3. Weight gain may occur as your patient’s mood improves.

4. 78% of people believe that antidepressants are addictive-address this issue!

5. Sexual dysfunction can be a problematic side effect for patients.

6. Serotonin withdrawal can occur when antidepressants are abruptly stopped.

7. Suicide risk (depending on location)

Post-Test Question 1

What depression screening tool is the most widely used and recommended in primary care treatment settings?

A. Beck Depression Inventory (BDI)

B. Hamilton Depression Rating Scale (HAM-D)

C. Patient Health Questionnaire (PHQ-9)

D. Geriatric Depression Scale (GDS)


Which of the following medications is recommended as a first-line treatment for a first episode of depression?

A. Lithium

B. Bupropion

C. Doxepin

D. Aripiprazole


Which of the following is considered a protective factor against suicide completion?

A. Older age

B. Experiencing psychosis

C. Bereavement

D. Religion

Take Home Points

• Depression is a common mental health disorder that can be detected early with proper screening.

• Once depression is identified, treatments may include psychotherapy and antidepressant therapy.

• Pharmacists can play an integral role in educating patients on the signs of depression and offering community resources on suicide prevention.

Speaker Contact Information

Kelly N. Gable, Pharm.D., BCPP

SIUE School of Pharmacy

200 University Park Drive

Edwardsville, IL 62025

[email protected]

mailto:[email protected]

focusing on depression in the community - ipha 2016- final.pdf · dosing adverse effects clinical...

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