Focusing on Depression in the Community Kelly N. Gable, Pharm.D., BCPP Associate 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 Chronic Pain Sleep Changes Social Isolation Appetite Changes Interest Lacking Tearfulness Headaches Poor Focus Depressed Mood Energy Decrease Guilt Hopelessness Irritability Excessive Worry
Medical Causes of Depression Medications Cardiovascular Agents: methyldopa, reserpine, clonidine, beta-blockers (propranolol) Sedative-hypnotics: alcohol, benzodiazepines, barbiturates, chloral hydrate Hormones: corticosteroids, progesterone, estrogen withdrawal, anabolic steroids Others: interferon, isotretinoin, varenicline, withdrawal from stimulants (cocaine, methamphetamine) Medical Conditions 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) 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 2 nd episode 2 episodes: 70% will have a 3 rd episode 3 episodes: 90% will have a 4 th 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 risk Screening 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
First Episode Depression 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 response 3. Family history of response to medication 4. Safety in overdose 5. Chronicity of the disorder 6. Adverse effect profile 7. Patient age 8. Concurrent medical illness (HTN, seizure disorder) 9. Concurrent medications (drug interactions) 10.Adherence (dosing schedule) 11.Cost
Selection of Initial Antidepressant Bupropion Mirtazapine Antidepressant Choices SNRIs TCAs SSRIs
Selective Serotonin Re-Uptake Inhibitors (SSRIs): Dosing & Clinical Pearls Dosing *Adverse Effects Clinical Pearls Fluoxetine (Prozac ) 20 80 mg/day Paroxetine (Paxil ) 10 60 mg/day Sertraline (Zoloft ) 50 200 mg/day Insomnia, activation Prozac Weekly, Sarafem Good alternative for nonadherence (t ½ ~7 days) Constipation, dry mouth, sedation Shortest t ½ (< 24 hours) & high serotonin withdrawal Most well-studied for anxiety disorders Nausea, diarrhea Food enhances bioavailability by 40% Less CYP450 drug interactions Fluvoxamine (Luvox ) 50 300 mg/day Citalopram (Celexa ) 20 40 mg/day Escitalopram (Lexapro ) 10 20 mg/day Sedation Dose-dependent QTc prolongation Generally welltolerated More CYP450 drug interactions Only FDA-indicated for OCD FDA notification 2011: should no longer be used at doses > 40 mg/day due to QTc prolongation Less CYP450 drug interactions 10 mg Lexapro = 20 mg Celexa *All SSRIs can cause nausea, headache, sexual dysfunction.
First Episode Depression 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- HT 2A, histamine 1 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 )
Selection of Initial Antidepressant Bupropion Mirtazapine Antidepressant Choices SNRIs TCAs SSRIs
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Dosing Adverse Effects Clinical Pearls Venlafaxine (Effexor ) Desvenlafaxine (Pristiq ) Duloxetine (Cymbalta ) 150 225 (XR) or 375 (IR) mg/day 50 100 mg/day 40 60 mg/day Nausea, headache, insomnia, sweating, sexual dysfunction Similar tolerability profile to venlafaxine Nausea, insomnia, headache, sexual dysfunction, increase in blood pressure, sweating Mild anticholinergic: dry mouth, constipation, urinary retention Tolerability worse with IR formulation diastolic blood pressure (dose-related > 225 mg/day; 9% at doses > 300 mg/day) Active metabolite of venlafaxine Studied for vasomotor symptoms of menopause 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- 2013 Active 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 alpha 2 receptors increasing 5-HT & NE release; blocks postsynaptic 5-HT 2/3 & H 1 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- HT 1A 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?
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)
Depression with Medical Complications. 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
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 & pediatric patients (< 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): selfinjury in which a person has no intent to die
Suicide Risk/Protective Factors Risk 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 Protective Factors 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 addictiveaddress 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)
Post-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
Post-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
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 kgable@siue.edu