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Major Depressive Disorder: Recognition and Management in Primary Care Dr. Levkovitz Y. Director Day-Hospital & Cognitive and Emotional Laboratory, Shalvata Mental Health Center, School of Medicine, Tel Aviv University, Israel. Objectives To be more knowledgeable about recognizing and treating depression To increase comfort in managing depression in primary care Causes of Disability by Illness Category United States and Canada 15-44 years old Mental Illness* Alcohol and drug use Injuries, including self-inflicted Respiratory disease Musculoskeletal disease Sense organ disease Cardiovascular disease Migraine Infectious disease, excluding HIV 0 5 WHO World Health Report 2002 10 15 20 25 30 35 40 Causes of Disability by Specific Illness United States and Canada 15-44 years old Unipolar depression Alcohol use Drug use Bipolar disorder Schizophrenia Hearing loss Migraine Iron deficient anemia Diabetes mellitus 0 5 WHO World Health Report 2002 10 15 20 25 30 Epidemiology Major Depressive Disorder (MDD) is the one of the most common mental disorders in primary care settings The prevalence of current MDD in primary care settings has been found to range from 9.2% to 13.5% MDD may occur at any age Natural History of Major Depression Recurrent, episodic disorder in > 50% Residual symptoms persist between episodes in 20-35% (partial remission) Systemic disorder . Most serious complication is suicide; others include marital, parental, social, and vocational difficulties. מקרה מספר 1 מורן בת , 30נשואה ואם לבת (בת . )5 הגיע לרופא המשפחה ומתארת עייפות רבה בחודשיים האחרונים .מורן עובדת כמזכירה ומתארת כי היא מבצעת שגיאות רבות בעבודתה .המעסיק שלה מעיר לה לאחרונה על שגיאותיה .מרגישה כי לאחרונה קשה לה יותר להתרכז .מדווחת על מריבות ומחלוקות בזמן האחרון עם בעלה בשל לחץ כלכלי בבית .כשמתעוררת בבוקר מרגישה עייפה ו "לחוצה מהמחשבה שהיא צריכה ללכת לעבודה". דיווח על התקפי פלפיטציות וכאבים בחזה. פחות מתעניינת בילדים ומרגישה שפחות משקיעה בהם. דיון ( מקרה )1 • איזה שאלות היית רוצה לשאול את מורן? מקרה מספר ( 1המשך) לאחר שנשאלה מספרת כי מקיצה משנתה בשלוש לפנות בוקר עם מועקה בחזה .לא הולכת לשיעורי "פילאטיס" והתעמלות במועדון השכונתי .מבשלת למשפחתה אך קיימת ירידה בתאבון .לא בטוחה אם יש שינוי במשקל. מרגישה בטוחה בנישואיה אבל מרגישה כי בעלה פחות מתעניין בה כי היא שווה פחות במיוחד כי יש לה פחות עניין בקיום יחסי מין עימו .מפחדת כי בעלה יעזוב אותה. מרגישה אשמה ביחס לילדיה ולבעלה .מרגישה כי צריכה להיענש והתאבדות תפתור את בעיותיה .משתמשת יותר ביין אדום כדי שתוכל לישון. דיון ( מקרה )1 •האם אתה צריך לראות את בעלה? •מה תעשה אם היא מסרבת לדבר עם בעלה כי היא מפחדת שידע כי היא חוששת לנאמנותו? מקרה מספר 1 מורן בת , 30נשואה ואם לבת (בת . )5 הגיע לרופא המשפחה ומתארת עייפות רבה (עצב ?) בחודשיים האחרונים .מורן עובדת כמזכירה ומתארת כי היא מבצעת שגיאות רבות בעבודתה .המעסיק שלה מעיר לה לאחרונה על שגיאותיה .מרגישה כי לאחרונה קשה לה יותר להתרכז .מדווחת על מריבות ומחלוקות בזמן האחרון עם בעלה בשל לחץ כלכלי בבית .כשמתעוררת בבוקר מרגישה עייפה ו"לחוצה מהמחשבה שהיא צריכה ללכת לעבודה" .דיווח על התקפי פלפיטציות וכאבים בחזה. פחות מתעניינת בילדים ומרגישה פחות משקיעה בהם. מקרה מספר ( 1המשך) לאחר שנשאלה מספרת כי מקיצה בשנתה בשלוש לפנות בוקר עם מועקה בחזה .לא הולכת לשיעורי "פילאטיס" והתעמלות במועדון השכונתי .מבשלת למשפחתה אך קימת ירידה בתאבון .לא בטוחה אם יש שינוי במשקל. מרגישה בטוחה בנישואיה אבל מרגישה כי בעלה פחות מתעניין בה כי היא שווה פחות במיוחד כי יש לה פחות עניין בקיום יחסי מין עימו .מפחדת כי בעלה יעזוב אותה. מרגישה אשמה ביחס לילדיה ולבעלה .מרגישה כי צריכה להיענש והתאבדות תפתור את בעיותיה .משתמשת יותר ביין אדום כדי שתוכל לישון. Recognition Depression is difficult to diagnosis in primary care and often goes undetected: depressed mood typically not presenting complaint competing demands (acute and chronic illnesses) limited resources and time Major Depression: Four Hallmarks Depressed Mood. Anhedonia: loss of interest or pleasure Physical Symptoms: sleep disturbance, low energy, appetite or weight change, psychomotor changes Psychological Symptoms: low self-esteem, poor concentration, suicidal ideation/obsession surrounding death. Assessing for Depression and Anhedonia Do not ask patient: “Are you Depressed?”, INSTEAD, Ask: “How has your mood been?” Ask about Anhedonia: “What are you doing for fun?” OR: “Does your (pain,anxiety, grief, whatever symptoms patient mentions) keep you from doing all the things you enjoy?” דיון ( מקרה )1 • מה הצעד הבא? •האם תרצה לדעת פרטים נוספים על משפחתה ? •האם תרצה לדעת פרטים עליה או על עברה? •אילו בדיקות דם תרצה להזמין? Risk Factors Prior episode of depression Family history of depressive disorder Prior suicide attempt Female gender Medical conditions Lack of social support Stressful life events Current substance use )1 דיון ( מקרה אבחנה מבדלת •Substance Induced Disorder ? •Mood Disorder ? •Anxiety Disorder ? •Personality Disorder ? •Relationship distress, financial stress related ?? •Medical Conditions ? •Medications ? Dependence/Withdrawal - 9.2% (Warner, 1995) - 20% (Hall, 1994 ) - anger, irritability, aggression - aches, pains, chills - depression - inability to concentrate - sleep disturbance - slight tremors - decrease in appetite - sweating - craving 3 to 7 days, to several weeks after abstinence (Haney, 1999) Organic Illnesses Associated with Depression Rheumatologic - systemic lupus erythematosus, rheumatoid arthritis Cardiac - mitral valve prolapse. Endocrine - hyperthyroidism, hypothyroidism, diabetes mellitus, hypercalcemia, Cushing’s syndrome University of NSW Chronic fatigue syndrome What is chronic fatigue syndrome? Definition • Unexplained, persistent or relapsing fatigue, that is: – – – – University of NSW • Four or more of: – impaired short term memory or concentration – sore throat of new, definite onset and – tender lymph nodes – muscle pain not due to exertion – joint pain not relieved by rest – headaches associated with a – unrefreshing sleep substantial reduction in daily activities – post-exertional malaise Fukuda K et al. Ann Intern Med 1994; 121: 953-9. Drugs Commonly Associated with Depression • • • • • • Benzodiazepines Cimetidine Beta-blockers Corticosteriods Oral contraceptives Indomethacin University of NSW Assessing Risk of Suicide Assess risk factors: PRIOR ATTEMPTS Family history of suicide Hopelessness Demographics Caucasian, male, elderly, lives alone Clinical Substance abuse, psychosis, potentially terminal illness Assessing for Suicide Use a gradual, sensitive approach to raise the subject: How does the future look to you? Living with (pain/anxiety/patients’ symptoms) can be very difficult. Do you sometimes wish your life was over? Have you had thoughts that you would be better off dead? Have you had thoughts of hurting yourself? Have you thought about how you might hurt yourself? When to Consider Involving Psychiatry Suicidal ideation Psychotic symptoms Manic symptoms Current substance abuse Severe psychosocial problems Interventions: What can be done? Depression is one of the most treatable mental illnesses • 70% - 75% of all depressed people respond to treatment • almost all who receive treatment experience some relief in symptoms Medication Psychotherapy Electroconvulsive Therapy Watchful waiting Management of Depression Give an adequate trial of treatment (therapeutic dose for 6-8 weeks) Follow closely until patient responds Change treatment if patient doesn’t respond Continue medication for 6-9 months minimum. If patient has a history of 2 or more previous depression episodes, continue for 2 years or more. Overview of Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs): fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxet), citalopram (Lustral) Selective Serotonin Norepinepherine Reuptake Inhibitors (SNRIs): venlafaxine (Effexor), Duloxetine (Cymbalta). Medications With Unique Mechanism of Actions (MOA): bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone) Older Agents (Tricyclic antidepressants or TCAs): desipramine, nortriptyline Therapeutic vs. Side Effects Therapeutic effects Effects of antidepressant treatment Side effects 0 1 2 3 Time in weeks 4 Side Effects Are relatively common Are the #1 reason patients give for stopping medications Therefore: Talk to patients about common side effects Wait - many side effects resolve with time Consider reducing the dose temporarily Consider changing to another type of medication Consider changing timing of medication Adjunctive Medications Anxiety Consider short term use of a benzodiazepine Insomnia Trazodone – warn about priapism Antihistamines (hydroxyzine, diphenhydramine) Sexual Dysfunction sildenafil מקרה מספר 1 ליאם ,בן ,24סטודנט באוניברסיטת תל אביב. מתואר כ "ביישן ומופנם" .יש לו קשיים בחברה ואפיזודות של פאניקה באירועים חברתיים. לאחרונה הבחין בעליה בתדירות התקפי החרדה באירועים בהם היה צריך להציג מעבודותיו. ב 4חודשים האחרונים מדווח על ישנוניות ועייפות. הוא מאחר לכיתה ונרדם בשיעורים .כשהוא נמצא בכיתה הוא מרגיש דחף לספור את חבריו לכיתה 3פעמים ולאחר לספור את התלמידים הלובשים חולצות כחולות .הוא מוצא את הספירה "מלחיצה". הוא מרגיש חייב לספור כל פרק בספר פעמים. דיון ( מקרה )1 • איזה שאלות היית רוצה לשאול את ליאם ? מקרה מספר ( 1המשך) ליאם מדלג על ארוחות כי איננו רעב .הוא הפסיק לראות את תכנית הטלויזיה האהובה עליו ולצאת עם הכלב שלו. הוא מדווח על ירידה משמעותית בריכוז וחווה ירידה בזיכרון. מרגיש כי הוא חייב להפסיק ללמוד כי הוא מבזבז את כספם של הוריו והוא "כאב ראש" למרצים. הוא משתמש במריחואנה כדי להרגיע את עצמו ,אבל כעת לא מרגיש כי זה עוזר לו. נמאס לו להמשיך ככה. )1 דיון ( מקרה אבחנה מבדלת •Major Depressive Episode with some Atipycal features, with obsessions and compulsions, History of Social Anxiety Disorder ? •Why not just SAD? •Why not Mixed Anxiety and Depression? Depression Features Specifiers Melancolia: •Either loss of pleasure or lack of reactivity to usually pleasurable stimuli. >3 of: prevasive non reactive sadness-melancholic, depression worse in the morning, early morning awakening, marked psychomotor retardation or agitation significant anorexia or weight loss, excessive or inappropriate guilt. Atypical: •Reactivity of mood to positive events. •>2 of: significant weight gain or increased appetite, hypersomnia, “leaden paralysis” or long standing pattern of interpersonal rejection sensitivity. Thanks ! Depression in Primary Care Depression In Western Industrialized Nations (DSM-IV): Males: 2-3% of population at any given time, and 5-12% for population in lifetime. Females:5-9% of population at any given time, and 10-25% for population in lifetime. Percent of mental disorders accounted for by depression: Males (up to) 15%, Females (up to) 45% (rough estimate). In primary care practices 5-9% patients at any given time have Major Depression (it is estimated that only one third to one half are recognized by practitioners). Consequences of Untreated Depression Depression is the 2nd leading cause of disability in industrialized countries Depression associated with: 2x increased risk of death overall 26x increased risk of suicide Impaired social functioning Consequences of Untreated Depression (continued) Depressed patients visit primary care provider 3x more than non-depressed patients 2-5x increase in days absent from work Cost of depression in US in 1990 estimated to be $44 billion Making the Diagnosis Depression Disorders Major depressive disorder (MDD) Minor (subthreshold) depression Adjustment disorder with depressed mood Dysthymia Diagnostic Criteria for Major Depression (DSM-IV) Major depression is present when the patient has had at least 5 of the 9 following symptoms for a minimum of two weeks. One of the symptoms must be either: 1. 2. Depressed mood-- or -Loss of interest or pleasure -- and - Diagnostic Criteria (continued) 3. Significant change in weight or appetite 4. Insomnia or hypersomnia 5. Psychomotor agitation or retardation 6. Fatigue or loss of energy 7. Feelings of worthlessness or guilt 8. Impaired concentration or ability to make decisions 9. Thoughts of suicide or self-harm Diagnostic Criteria (continued) Symptoms must be accompanied by functional impairment in one or more of the following domains: work/school doing things at home relationships with other people PHQ9 includes 10th question addressing functional impairment Depression Coexisting with Other Behavioral Disorders Alcohol Dependency Anxiety Disorders (panic attacks, phobias) Eating Disorders Obsessive Compulsive Disorder Somatization Disorders Personality Disorders Grief and Adjustment Reactions Minor depression Patient has 2 to 4 of the 9 symptoms listed above Symptoms present for at least two weeks One of the symptoms must be either item 1 (depressed mood) or item 2 (loss of interest or pleasure) Selective Serotonin Reuptake Inhibitors (SSRIs) fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa) Side effects: Insomnia or sedation, agitation/restlessness, GI distress, sexual dysfunction, headache Absolute contraindication: MAOI (not selegiline) Relative contraindication: Mania history (manic depression) Dysthymia Depression present more days than not, for 2 years or more Well period can not last more than 2 months during this time Depression Coexisting with Other Medical Disorders Stroke Dementia Diabetes Coronary Artery Disease Cancer Chronic Fatigue Syndrome Fibromyalgia Response and Remission defined Hamilton Depression Rating Scale (HAM-D): 17 Items, Total Score 0 - 52 HAM-D17 Scores 15 7 Depression (Major Depressive Disorder) Response 50% reduction from baseline HAM-D score Remission: HAM-D Score 7 References: 1. Frank E. Conceptualization and rationale for consensus definition terms in MDD, Arch Gen Psych. 1991; 48:851-855. Drug Interactions Sertraline and citalopram have no clinically significant drug interactions through the CYP450 system Fluoxetine and paroxetine are potent 2D6 inhibitors Nefazodone is a potent 3A4 inhibitor Common Barriers to Treatment Practical Barriers Ethnic/Cultural barriers Patient doesn’t agree with diagnosis or plan Patient doesn’t understand treatment plan Patient is afraid of becoming addicted to antidepressants Common Barriers to Treatment (Continued) Side effects Patient forgets to take medications or runs out early Formulary restrictions Friends or family are not supportive Treatment is ‘not working’; patient feels hopeless Treatment ‘is working’; patient is better and wants off Adherence 20-50% of patients “drop out” in the first month of treatment 30-50% of patients don’t have a complete response to the initial treatment If patient is not better at 8 weeks, consider changing medication, adding psychotherapy, or getting a psychiatric consultation Improving Medication Adherence Tell patients: Medications take time to work Medications are not addictive Take medications every day as ordered Take medications even if you feel better Do not stop medication before first contacting your physician Engage in pleasant activities Call your provider if you have questions What To Do If Patients Don’t Get Better Wrong diagnosis? Insufficient dose? Insufficient length of treatment? Problems with barriers to adherence? Side effects? Other complicating factors? Wrong treatment? Continue Medication for 6-9 Months or More Medications should be continued for 6-9 months after the patient gets better People at high risk for relapse (those with at least two prior episodes of major depression, dysthymia, or residual depressive symptoms) should get a full dose of medication for 2 years or more to prevent recurrences See patients at least every 3 months What To Do If Patients Relapse Assess adherence to medication regimen Examine for new stressors Restart treatment at the last effective dose of antidepressants or consider an increase in dose if patient is still taking medication Consider adding psychotherapy Consider psychiatric consultation Preparing the Patient for a Mental Health Referral Bring up the possibility of a mental health consultation when first presenting the diagnosis of depression to the patient. The request for a mental health consultation is simply a matter of obtaining another professional opinion. Draw the analogy of referrals made to other medical specialist, like cardiologists, endocrinologists, etc. Side Effects of Other Antidepressants bupropion (Wellbutrin) Main contraindication is seizure disorder or eating disorder Also effective for smoking cessation Less sexual dysfunction than others mirtazapine (Remeron) Sedation Weight gain venlafaxine (Effexor): Relative contraindication if HTN is present nefazodone (Serzone): Carries a black box warning for liver failure Antidepressant Dosing Once a day dosing: Give sedating meds at bedtime (paroxetine, mirtazapine, nefazodone) Activating meds (fluoxetine) in the morning Starting dose is lower with the elderly, with the medically ill, and if there is a comorbid panic disorder. Titrate to therapeutic dose as tolerated by side effects