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Learning Objectives

• Importance of screening for depression in the primary care setting. • How to use screening tools for depression in an effective way. • Learn changes in DSM‐5 classification that could help with a more accurate diagnosis of subtypes of depressive disorder. • Review evidence‐based treatment options including AITALA GIRON , M.D. antidepressants vs psychotherapy or both.

Case Scenario  Depression is among the leading cause of disability in adults in the USA . Ms. G is a 54 year old female, mixed raced. She has been your patient for that last 3 years.

 Her medical history is positive for Type II Diabetes (diagnosed 6  Is very common for patients to present first to a month ago), obesity and HTN. primary care setting to seek help .  Her last laboratory results where remarkable for : AIC% Hb of 7.2  Medication regimen includes :Metformin 500 mg BID, Metoprolol 50 mg per day. Simvastatin 20 mg per day.  Her oldest son is leaving for college and is she is having marital  Screening with accurate diagnosis and then effective problems. treatment will improve clinical outcome.  Presents to follow up complaining of “sleeping difficulties”.  Reports being tired all the time and reports anhedonia .  She has sad affect and starts crying that she has gained 30 lb. in the last  DSM‐5 uses available evidence and data to fine tune 6 months, has no interest in sex, difficulties concentrating and is having hot flashes. the diagnosis of depressive disorders.  She think this is why her husband is not interested in her any longer .

Depression and Anhedonia Prevalence of Major Depression  Major Depression diagnosis is especially difficult when they occur in an individual who also has a general  According to the World Health Organization (WHO; medical condition (e.g., cancer, stroke, myocardial 2010), major depression carries the heaviest burden of infarction, diabetes, pregnancy). disability among mental and behavioral disorders  Some of the criterion signs and symptoms of a major depressive episode are identical to those of general medical conditions (e.g., weight loss ,weight gain ,  In 2015, an estimated 16.1 million adults aged 18 or fatigue, hypersomnia, insomnia). older in the United States had at least one major  Nonvegetative symptoms of dysphoria, anhedonia, depressive episode in the past year. guilt or worthlessness, impaired concentration and suicidal thoughts should we asses and help with the differential diagnosis .  This number represented 6.7% of all U.S. adults.

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Prevalence of Major Depression among Major Depression with Severe US Population 2015 Impairment Among Adults in 2015

Rates of Clinical Diagnosis of Depression among USA Workers Depression Among USA Workers  Workers with a diagnosis of depression miss an estimated 68 million additional days of work each year  Results in an estimated cost of more than $23 billion in lost productivity annually to U.S. employers.  Workforce with diagnosis of depression misses average 8.7 missed work days each year due to poor health.  Workers with no depression miss an average of 4.6 work days per year.

Witters D, Liu D, Agrawal S. Depression costs http://www.gallup.com/poll/163619/depression - costs-workplaces-billion-absenteeism.aspx.

Inflammation and Depression Depression and Diabetes  Inflammatory Markers elevated in Depression  A meta‐analysis of cross‐sectional studies in 2006, depression had a includes :Interleukin 1B ,Tumor Necrosis Factors , prevalence of 17.6% among those with Type II Diabetes and 9.8% among those without Type II Diabetes C‐Reactive protein.  Patients with a history of childhood trauma have an  Comorbid depression and diabetes are particularly common among elevated risk not only for depression but also for a women, with female preponderance noted in the 2001 findings (28% variety of common chronic medical diseases. for women vs. 18% for men)  A relationship exists between childhood maltreatment and elevations in plasma inflammatory markers in  In a large study (143,943 primary care patients with major depressive adulthood. disorder), Type II DM was present in 9.3% of the major depressive disorder population, in comparison with 4.3% of those without  Depressed male patients with a history of early‐life depression stress demonstrate an increased inflammatory response to acute psychosocial stress. Smith DJ, et al: Depression and multimorbidity:J Clin Psychiatry 2014; 75:1202–1208

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Depression and Diabetes DSM‐5 Depressive Disorders  There is speculation that the structural and neurochemical changes associated with diabetes induce depressive  Disruptive Mood Dysregulation Disorder symptoms  Major Depressive Disorder  Persistent Depressive Disorder (Dysthymia)  The neuroinflammatory changes induced by diabetes and the direct impact of altered insulin metabolism on the  Premenstrual Dysphoric Disorder brain are biologically plausible mechanisms by which those  Substance/Medication‐Induced Depressive Disorder with diabetes could be predisposed to depression.  Depressive Disorder Due to Another Medical Condition  Diabetes‐related biochemical changes induce cognitive disturbances and can adversely affect emotional processing and reward circuitry.

DSM‐5 Criteria for Major Depression DSM‐5 Criteria for Major Depression Disorder Disorder  Five (or more) of the following symptoms have been present during the same  Psychomotor agitation or retardation nearly every day (observable by 2‐week period and represent a change from previous functioning; at least one others, not merely subjective feelings of restlessness or being slowed of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. down).  Note: Do not include symptoms that are clearly attributable to another medical condition.  Fatigue or loss of energy nearly every day.  Feelings of worthlessness or excessive or inappropriate guilt (which may be  Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by delusional) nearly every day (not merely self‐reproach or guilt about being others (e.g., appears tearful). (Note: In children and adolescents, can be sick). irritable mood.)  Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).  Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account  Recurrent thoughts of death (not just fear of dying), recurrent suicidal or observation). ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.  Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in  The symptoms cause clinically significant distress or impairment in social, appetite nearly every day. (Note: In children, consider failure to make occupational, or other important areas of functioning. expected weight gain.)  The episode is not attributable to the physiological effects of a substance or to  Insomnia or hypersomnia nearly every day. another medical condition.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric American Psychiatric Association. Diagnostic and Statistical Manual Publishing; 2013. of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

Major Depression Disorder Major Depression Disorder  The symptoms have to occur simultaneously during a 2‐week period and to have undergone a change from  Anhedonia is the second anchor criteria of depression. previous functioning.  Appetite change and unintended weight loss reflect the physical symptoms related to depression  Either depressed mood or anhedonia (loss of interest or pleasure) must be one of the symptoms.  Sleep disturbances. The individual feels that he or she is not getting enough sleep and experiences fatigue or exhaustion  The depressed mood of a major depressive episode is during waking hours. objective, is sustained, and preoccupies most of the  Insomnia include initial insomnia ,middle insomnia and time nearly every day. terminal insomnia (early awakening and difficulty falling  The patient can describe it as a profound sense of back asleep) hopelessness or internal emptiness.  Altered psychomotor activity is expressed in agitation or retardation

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Major Depression Disorder Depression and Comorbid Conditions

 Fatigue and loss of energy may be subjective,  Comorbid Conditions in Depression objective, or both. MDD: 72% lifetime prevalence  Thoughts and cognitive processes are disrupted. May have feelings of unworthiness or excessive or Anxiety Disorder: 59% inappropriate guilt Substance Use Disorder:24%  Diminished ability to think or concentrate. The Impulse Control Disorder :30% capacity to perform at previously documented levels is impaired.  Recurrent thoughts of death and suicide are a common feature of the depressive episode

Major Depression Disorder Major Depression Disorder

 Average age of onset: 29 years  Risk of relapse after one episode: 50 %  Average length of episode 3 month  Risk of Relapse after three episodes: >80%  63% of patients full recovery in 6 months  Family studies shows 2‐ 3 times more frequent in  80% of patients full recovery in 2 years relatives of those with Major Depression than in the  5‐10 % develop Bipolar Disorder general population .   15% of patients commit suicide Concordance rate is 50% in monozygotic twins vs 20% in dizygotic

Depression and Sleep DSM‐5 Criteria for Premenstrual Dysphoric Disorder  There is loss of deep sleep  In the majority of menstrual cycles, at least five symptoms  More frequent awakening and arousal must be present in the final week before the onset of menses, start to improve within a few days after the onset of  Reduced REM latency(decrease time from sleep onset menses, and become minimal or absent in the week post to REM onset) menses.  Increase REM Density  One (or more) of the following symptoms must be present:   Marked affective lability (e.g., mood swings; feeling suddenly sad or Antidepressants suppress REM sleep( correlates with tearful, or increased sensitivity to rejection). response)  Marked irritability or anger or increased interpersonal conflicts.  Marked depressed mood, feelings of hopelessness, or self‐ deprecating thoughts.  Marked anxiety, tension, and/or feelings of being keyed up or on edge. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

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DSM‐5 Criteria for Premenstrual DSM‐5 Criteria for Premenstrual Dysphoric Disorder

Dysphoric Disorder  Note: The symptoms in Criteria A–C must have been met for most menstrual cycles that occurred in the preceding year.  One (or more) of the following symptoms must  The symptoms are associated with clinically significant distress additionally be present, to reach a total of five symptoms or interference with work, school, usual social activities, or when combined with symptoms from Criterion B above. relationships with others .  The disturbance is not merely an exacerbation of the symptoms  Decreased interest in usual activities (e.g., work, school, friends, of another disorder, such as major depressive disorder, panic hobbies). disorder, persistent depressive disorder (dysthymia), or a  Subjective difficulty in concentration. personality disorder (although it may co‐occur with any of these  Lethargy, easy fatigability, or marked lack of energy. disorders).  Marked change in appetite; overeating; or specific food cravings.  Criterion A should be confirmed by prospective daily ratings  Hypersomnia or insomnia. during at least two symptomatic cycles.  A sense of being overwhelmed or out of control.  The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment)  Physical symptoms such as breast tenderness or swelling, joint or or another medical condition (e.g., hyperthyroidism). muscle pain, a sensation of “bloating,” or weight gain.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

Premenstrual Dysphoric Disorder Premenstrual Dysphoric Disorder

 Somatoform discomforts and sensations.  PMDD has been shown to be a clinically significant  The disorder manifests in the week prior to the onset psychiatric disorder with discriminate biological markers of menses, with increasing intensity that usually peaks immediately prior to the onset of menstruation, and  Is treatable with a variety of pharmacological, hormonal, and psychotherapeutic treatments then wanes quickly thereafter.  Involves changes specific to the menstrual cycle, which  There is notable clinical distress or interference with include emotional lability, changes in volition, energy, social, vocational, or personal relationships. concentration ability, and self‐perception.  The symptoms must have occurred in most (> 50%)  Physiological disruptions in sleep and appetite are menstrual cycles during the past year, and must have common an adverse effect on work or social functioning.

Premenstrual Dysphoric Disorder Screening for Depression in Adults: Clinical Summary: US Preventive Services Task Force  The 12‐month prevalence of PMDD is between 1.8% and 5.8 USPSTF Grades Mean and Suggestions for Practice‐Grade B:  Symptoms emerge in early adulthood  Recommends the service. There is high certainty that the  Most do not seek treatment until they are over age 30 net benefit is moderate, or there is moderate certainty that  PMDD symptoms improve as a result of ovulatory changes, the net benefit is moderate to substantial. such as during pregnancy and after menopause  Suggestions for Practice‐ Offer or provide this service.  Specific etiology for PMDD is not known‐ some include declining levels of ovarian steroid hormones in the late  Population ‐Adults aged ≥18 y luteal phase of the menstrual cycle and a hormonal ratio imbalance related to high estrogen levels compared to  Recommendation: Screen for depression, with adequate progesterone levels. systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow‐up.

U.S. Preventive Services Task Force. September 2016. https://www.uspreventiveservicestaskforce.org/

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Screening for Depression in Adults: Screening for Depression in Adults: Clinical Summary Clinical Summary Risk Assessment:  Women, young and middle‐aged adults, and nonwhite (mixed) persons Screening Tests: have higher rates of depression, as do persons who are undereducated,  Depression screening instruments include: the Patient previously married, or unemployed. Health Questionnaire(PHQ‐9) in various forms. The  Persons with chronic illnesses, other mental health disorders, or a Hospital Anxiety and Depression Scales in adults, the family history of psychiatric disorders are also at increased risk. Geriatric Depression Scale in older adults, and the

 Risk factors in older adults include disability and poor health status related to Edinburgh Postnatal Depression Scale in postpartum and medical illness, complicated grief, chronic sleep disturbance, loneliness, and pregnant women. history of depression.  Positive screening results should lead to additional  Risk factors during pregnancy and postpartum include poor self‐esteem, assessment including severity of depression and comorbid childcare stress, prenatal anxiety, life stress, decreased social support, single/unpartnered relationship status, history of depression, difficult infant psychological problems, alternate diagnoses, and medical temperament, previous postpartum depression, lower socioeconomic status, and unintended pregnancy conditions

U.S. Preventive Services Task Force. September 2016. U.S. Preventive Services Task Force. September 2016. https://www.uspreventiveservicestaskforce.org https://www.uspreventiveservicestaskforce.org

Screening for Depression in Adults: Screening for Depression in Adults: Clinical Summary Clinical Summary Treatment and Interventions Screening Interval:  Effective treatment of depression in adults generally includes antidepressants or specific psychotherapy  The timing and interval for screening for depression is approaches, alone or in combination. not known. A good approach might include screening all adults who have not been screened previously  Given the potential harms to the fetus and newborn child from certain pharmacologic agents, clinicians are  Then using clinical judgment in consideration of risk encouraged to consider evidence‐based counseling factors, comorbid conditions, and life events to interventions when managing depression in pregnant determine if additional screening of high‐risk patients or breastfeeding women is warranted U.S. Preventive Services Task Force. September 2016. https://www.uspreventiveservicestaskforce.org U.S. Preventive Services Task Force. September 2016. https://www.uspreventiveservicestaskforce.org

Screening for Depression in Adults: Patient Health Questionnaire PHQ‐9 Clinical Summary Balance of Benefits and Harms:  The net benefit of screening for depression in the general adult population is moderate.  There are adequate evidence that programs combining depression screening with adequate support systems in place improve clinical outcomes (reduction or remission of depression symptoms) in adults  There are convincing evidence that treatment of adults and older adults with depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.  There is adequate evidence that the magnitude of harms of screening for depression in adults is small to none

U.S. Preventive Services Task Force. September 2016. https://www.uspreventiveservicestaskforce.org

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Patient Health Questionnaire: PHQ‐9 Patient Health Questionnaire: PHQ‐9

Over the last 2 weeks, how often have you been bothered by any of the Symptoms occur: following problems?  Not at all  Little interest or pleasure in doing things  Feeling down, depressed, or hopeless  Several days  Trouble falling or staying asleep, or sleeping too much  More than half the days  Feeling tired or having little energy  Nearly every day  Poor appetite or overeating If you checked off any problems, how difficult have these  Feeling bad about yourself—or that you are a failure or have let yourself problems made it for you to do your work, take care of things or your family down at home, or get along with other people?  Trouble concentrating on things, such as reading the newspaper or watching television  Not difficult at all  Moving or speaking so slowly that other people could have noticed? Or  Somewhat difficult the opposite—being so fidgety or restless that you have been moving around a lot more than usual  Very difficult  Thoughts that you would be better off dead or of hurting yourself in  Extremely difficult some way

Depression Treatment Patient Health Questionnaire: PHQ‐9  Depression treatment begins with an antidepressant, typically from the SSRI class.  There are no consistently reliable biological or clinical markers Interpretation of Total Score support the use of one antidepressant over another.  1‐4 Minimal depression  Medication Should be for at least 3–5 weeks at a therapeutic dose to evaluate a drug’s efficacy.  5‐9 Mild depression  The time to remission is often as long as 8–12 weeks  10‐14 Moderate depression  If indicators of response at the 3‐ to 5‐week window, the patient  15‐19 Moderately severe depression is strongly advised to continue at the maximally tolerated therapeutic dose.  20‐27 Severe depression  Most SSRIs have biological half‐lives in the 24‐hour range, which makes them ideal for once‐daily  For most patients begin at the entry‐level dose and gradually (weekly) increase the dose as tolerated.

Antidepressant Medications Side effects and other Type Drug (trade name) Daily dosing Pharmacology Duration of Pharmacotherapy concerns TCA Amitriptyline (Elavil) 75–300 mg Inhibits reuptake of 5‐ Dry mouth, urinary HT and NE retention, sedation, Adequate trial : constipation, weight gain, hypotension, quinidine‐ • 4‐8 weeks at therapeutic dose like effect on heart conduction • Elderly may need at least 12 weeks SSRI Fluoxetine (Prozac) 20–80 mg Inhibits reuptake of 5‐ Sexual dysfunction, HT nausea, diarrhea, Sertraline (Zoloft) 25–200 mg insomnia, agitation, Paroxetine (Paxil) 10–60 mg tremors, dizziness, Treatment after remission rare hypo‐natremia, rare Citalopram (Celexa) 10–60 mg bruising, discontinuation • 6‐12 month after remission at full dose Escitalopram (Lexapro) 5–20 mg syndrome, drug–drug • Decide after that if maintenance treatment is needed interactions SNRI Venlafaxine (Effexor) 37.5–400 mg Inhibits reuptake of 5‐ Nausea, insomnia, HT and NE sedation, sexual Duloxetine (Cymbalta) 30–120 mg dysfunction, sweating, hypertension, discontinuation

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Antidepressant Medications Durations and Dosages of Second

Side effects and other Type Drug (trade name) Daily dosing Pharmacology concerns Generation Antidepressant MAOI Phenelzine (Nardil) 45–75 mg Irreversibly inhibits MAO from Hypotension, weight gain, sedation, Drug Duration Dosage, Comparative or Drug‐Specific breaking down into NE, 5‐HT, and dry mouth, sexual dysfunction, Tranylcypromine (Parnate) 30–60 mg dopamine dietary restrictions, risk of wk. mg/d Adverse Effects hypertensive crisis, life‐threatening drug–drug interactions Bupropion 12‐14 200‐450 Lower rate of sexual adverse events than escitalopram, fluoxetine, paroxetine, and Selegiline (Emsam 20, 30, or 40 mg At recommended doses, does not Weight gain, sedation sertraline [transdermal]) inhibit gut MAO‐A Atypical Mirtazapine (Remeron) 15–45 mg Improves 5‐HT and NE tone: ±2 Weight gain, sedation, abnormal Bupropion SR 14 150‐400 Lower rate of sexual adverse events presynaptic blocker on NE and 5‐HT dreams, dry mouth, hypotension, neurons constipation, rare agranulocytosis Citalopram 6‐820‐40 Possible increased risk for QT interval Blocks 5‐HT2A, 5‐HT2C, and 5‐HT3 prolongation and torsade de pointes (dosages >40 mg/d) Blocks H1

Bupropion (Wellbutrin) 75–450 mg in three Blocks reuptake of NE Agitation, restless insomnia, weight Escitalopram 12‐24 10‐20 None specific divided doses (maximal loss, anorexia, sweating, headache, Increases dopamine in frontal single dose, 150 mg) tremor, hypertension, rare seizures Fluoxetine 4‐96 10‐80 Lowest rates of discontinuation syndrome cortex SR 200–450 mg in two compared with other SSRIs Blocks dopamine transporter pump divided doses

XL 150–450 mg daily

Common Psychological Interventions to Durations and Dosages of Second Treat Depression Generation Antidepressant Intervention Description Acceptance and commitment therapy Uses mindfulness techniques to overcome Drug Duration wk. Dosage, mg/d Comparative or Drug‐Specific negative thoughts and accept difficulties Adverse Effects Cognitive therapy Helps patients correct false self‐beliefs and negative thoughts Fluvoxamine 52 40‐120 None specific Cognitive behavioral therapy Includes a behavioral component in Paroxetine 4‐54 20‐60 Highest rates of sexual dysfunction cognitive therapy, such as activity among SSRIs; higher rates of weight scheduling and homework gain; highest rates of discontinuation syndrome Interpersonal therapy Focuses on relationships and how to address issues related to them Sertraline 8‐49 50‐200 Higher incidence of diarrhea Psychodynamic therapy Focuses on conscious and unconscious feelings and past experiences Venlafaxine 8‐16 75‐375 Higher rates of nausea and vomiting; higher rates of discontinuations due to adverse events than SSRIs as a class; Third‐wave cognitive Targets thought processes to help highest rates of discontinuation behavioral therapy persons with awareness and acceptance syndrome

Modified from Ann Intern Med. doi:10.7326/M15‐2570 Modified from Ann Intern Med. doi:10.7326/M15‐2570

Key Points Key Points  Depressive disorders are a complex class of affect  Major depressive disorder is a clinical diagnosis. It is a disturbances involving volitional, emotional, cognitive, and common, treatable, and frequently recurrent and chronic psychological functioning. disorder that is often associated with other medical and psychiatric illnesses.  Assessment includes the dimensions of social,  Management of major depressive disorder may require the environmental, and biological elements. integration of psychological, social, and medical  Premenstrual dysphoric disorder shows many of the treatments. Medical management usually begins with an features of depression in the week prior to menses and SSRI. If the patient has no minimal response within 3–5 dissipates within a week following menstruation onset. weeks, the prudent course is to change or augment the This disorder responds quickly to selective serotonin current treatment plan as well as reevaluate the diagnosis. reuptake inhibitors (SSRIs).  Concurrent medical and psychiatric disorders should be managed accordingly

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Free Booklets and Brochures Free Booklets and Brochures  Chronic Illness & Mental Health: This brochure discusses chronic illnesses and depression, including symptoms, health effects,  www.nimh.nih.gov/health/publications/depression treatment, and recovery.  Depression and College Students: This brochure describes depression, treatment options, and how it affects college students.  Depression and Older Adults: Depression is not a normal part of aging. This brochure describes the signs, symptoms, and treatment Depression is a real options for depression in older adults. illness.  Depression: What You Need to Know: This booklet contains information on depression including signs and symptoms, treatment Treatment can help and support options, and a listing of additional resources. you live to the fullest  Postpartum Depression Facts: A brochure on postpartum extent possible, depression that explains its causes, symptoms, treatments, and how to even when you have get help. another illness.  Teen Depression: This flier for teens describes depression and how it differs from regular sadness. It also describes symptoms, causes, and treatments, with information on getting help and coping.

References References

 O’Connor E, et al .Screening for Depression in Adults: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No.  Anderson RJ et al: The prevalence of comorbid depression in adults with diabetes: a 128. AHRQ Publication No. 14‐05208‐EF‐1. Rockville, MD: Agency for Healthcare meta‐analysis. Diabetes Care 2001; 24:1069–1078 Research and Quality; 2016.  Roy T, Lloyd CE: Epidemiology of depression and diabetes: A systematic review. J  Witters D, Liu D, Agrawal S. Depression costs Affect Disord 2012; 142:S8–S21 http://www.gallup.com/poll/163619/depression ‐costs‐workplaces‐billion‐  Ali S, Stone MA, et al: The prevalence of co‐morbid depression in adults with type 2 absenteeism.aspx. diabetes: a systematic review and meta‐analysis. Diabet Med 2006; 23:1165–1173  Albert L. Siu ,MD, MSPH et all JAMA. 2016;315(4):380‐387.  Amir Qaseem, MD, PhD, MHA et al: Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the  American Psychiatric Association: Practice Guideline for the Treatment of Patients American College of Physicians Ann Intern Med. doi:10.7326/M15‐2570 With Major Depressive Disorder, 3rd ed. Arlington, VA, American Psychiatric Association, 2010  focus.psychiatryonline.org Focus Vol. 14, No. 2, Spring 2016  Smith DJ, et al: Depression and multimorbidity:J Clin Psychiatry 2014; 75:1202– 1208

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