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Management of Adolescent Depression Richard Idell, M.D. Prevalence • 3 to 5 years – 0.5 percent • 6 to 11 years – 1.4 percent • 12 to 17 years – 3.5 percent • Lifetime prevalence of depression in adolescence 11% Gender Differences • 2:1 Female to Male ratio, emerges during puberty • Before puberty 60% higher in boys Risk factors ●Low birth weight ●Family history of depression and anxiety ●Family dysfunction or caregiver-child conflict ●Exposure to early adversity (eg, abuse, neglect, or early loss) ●Psychosocial stressors (eg, peer problems and victimization [bullying], and academic difficulties) Risk Factors • Gender dysphoria and homosexuality, especially if youth is bullied • Negative style of interpreting events and coping with stress • History of anxiety disorders, substance use disorder, learning disabilities, attention deficit hyperactivity disorder, and oppositional defiant disorder • Traumatic brain injury • Chronic illness, especially if symptom and/or treatment burden yields chronic life disruptions Symptoms • Several domains – Psychological – Physical – Cognitive • Leading to change in behavior – Often what parents notice – Adolescents tend to reports thoughts and feelings more Symptoms-5 “SIGECAPS”/2weeks • Depressed or irritable mood – Gloomy, hopeless, everything is unfair, feeling helpless – Annoyed, grouchy, bothered, negative argumentative, low frustration tolerance – Reactive mood- cheered up by positive events • Thrill seeking, promiscuity, drug use • Rumination with depressed peers Symptoms • Diminished interest or pleasure (anhedonia) – hobbies, interests, and people as less interesting or fun than previously – "boring," "stupid," or "uninteresting.“ – Withdraw from friends Symptoms • Change in appetite or weight – Failure to gain weight – Weight gain Web: Pro-ana, Pro- mia, ASH • Ana- anorexia “support” (thinspiration) • Bulimia- bulimia “support” • ASH- suicide “pro-choice” Symptoms • Sleep disturbance insomnia, hypersomnia, – Initial insomnia – Middle insomnia – Terminal insomnia – Hypersomnia – Circadian reversal – Non-restorative sleep, tough to get up Symptoms • Psychomotor agitation or retardation – inability to sit still; pacing; or pulling or rubbing clothes, the skin, or other objects – psychomotor retardation: talk or move more slowly than is typical for them; in addition, speech volume or inflection may be decreased, and the amount of speech may be diminished. – Noticeable to others Symptoms • Fatigue or loss of energy – Lack of energy (anergia) manifests with feeling tired, exhausted, listless, and unmotivated. – Need to rest during the day, experience heaviness in their limbs, or feel like it is hard to initiate activities. – Parents may attribute lack of energy and motivation to laziness, an oppositional attitude, or avoidance of responsibilities. – Parents concerned that the patient has a general medical illness Symptoms • Feelings of worthlessness or guilt feelings of inadequacy, inferiority, failure, worthlessness, and guilt. – – – – – Self-critical Discounting positive self-attributes Dissatisfaction with themselves Lying about success or skills to bolster self-esteem Envy or preoccupation with the success of others, especially in comparison with self-evaluation – Belief that they deserve to be punished for things that are not their fault – Reluctance to try to do things because patients fear they will fail, and decide “what’s the use?” Symptoms • Impaired concentration and decision making • Not present before the depressive episode. – Thinking and processing of information may be slowed. – indecisive, which manifests as procrastination, helplessness, or ambivalence – Longer to complete homework and class work than before the depressive episode; school performance may thus decline. Recurring thoughts of death • Recurring thoughts of death or suicide – – Morbid thoughts are common in depressed teens – Active suicidal ideation of wanting to die – Hopelessness Psychosis • Psychosis – Major depression may include delusions and hallucinations (command auditory hallucinations telling patients to commit suicide) Functional impairment • School functioning, parents and peers, and daily activities and responsibilities. – Risk for engaging in health risk behaviors such as promiscuity • May reinforce and trigger new episodes: – – – – – Academic failure and school avoidance Interpersonal dysfunction with family, peers, and teachers Social withdrawal Negative attributions about the perceptions or intent of others Seeking reassurance excessively • Most notable during adolescence, when most teens strive to define themselves and establish a social role outside the family. • Impact on psychosocial outcomes in adulthood is not clear; some studies suggest adolescent depression is associated with functional impairment in adults, whereas other studies do not. Comorbidity • 60%-one other disorder • 50%- two disorders – Anxiety disorders – Attention deficit hyperactivity disorder (ADHD) – Disruptive behavior disorders (eg, oppositional defiant disorder and conduct disorder) – Substance use disorders – Eating disorders, learning disorders, and somatic symptom disorders, – Depressed patients are more likely to manifest health problems General Medical Problems • General medical — depression in adolescence may be associated with premature atherosclerosis and cardiovascular disease. • Increased inflammation, oxidative stress, and autonomic dysfunction • Cardiovascular risk factors: diabetes mellitus, obesity, sedentary lifestyle, and tobacco smoking are more prevalent among adolescents with major depression compared with the general pediatric population • Depression- moderate risk condition for early cardiovascular disease Course • Children – the average duration of depressive episodes ranged from 8 to 13 months – relapse or recurrence occurred in 30 to 70 percent • Adolescents – average duration of depressive episodes ranged from four to nine months, and that 90 percent of the episodes remitted within two years – one recurrence was observed in 20 to 70 percent – Adolescents with major depression are more likely to suffer depression in adulthood, compared with adolescents who are not depressed. • Recurrence — Risk factors for recurrence of pediatric major depression include: – – – – – – History of prior depressive episodes Presence of residual depressive symptoms Presence of comorbid disorders Environmental stressors Limited social supports Family history of recurrent unipolar major depression or other psychopathology Assessment • ASSESSMENT — psychiatric and general medical history, mental status, and focused laboratory tests: thyroid stimulating hormone, complete blood count, chemistries, and urine toxicology to screen for substances of abuse – Child or adolescent, parents and teachers, questionnaires (BDI etc.) – Culture – Suicidal and homicidal ideation and behavior – Look for comorbid conditions (psychiatric or physical) – Evaluate precipitants, stressors, and academic, social, and family functioning – Resist the diagnosis of depression and continue to seek a "medical" explanation for presenting symptoms. – Diagnosis of depression as reassuring, potential for relief Depression Diagnosis • Major depressive disorder • Persistent depressive disorder (dysthymia) – low grade depression lasting years • Unspecified depressive disorder • Disruptive mood dysregulation disorder – irritability, frequent major tantrums • Premenstrual dysphoric disorder • Substance/medication induced depressive disorder • Depressive disorder due to another medical condition Specifiers • Anxious distress • Atypical features (teens) • Reactive to pleasurable stimuli (ie, feels better in response to positive events) – – – – • Increased appetite or weight gain Hypersomnia (eg, sleeping at least 10 hours per day, or at least 2 hours more than usual when not depressed) Heavy or leaden feelings in limbs Rejection sensitivity Catatonia – Catatonic features are characterized by prominent psychomotor disturbances • Melancholic features- (elderly) • Loss of pleasure in most activities – – – – – – Unreactive to usually pleasurable stimuli (ie, does not feel better in response to positive events) Depressed mood marked by despondency, despair, or remorse Early morning awakening (eg, two hours before the usual hour of awakening) Psychomotor retardation or agitation Anorexia or weight loss Excessive guilt Differential • Adjustment disorder with depressed mood – Stressor in past 3 months, sadness, impaired functioning, doesn’t meet criteria for depression • Bipolar depression – Depression + episodic mania (not necessarily mood swings throughout the day) – Depression usually presents before mania • Reactive mood/sadness Treatment • Safety • Education • Treatment plan – Pharmacotherapy – Psychotherapy – Combination therapy (pharmacotherapy plus psychotherapy) – Assess psychosocial stressors, home, school, social – Lifestyle • Exercise, diet, stress reduction techniques Initial treatment • Combination therapy- TADS study – Faster response (higher response rate at 12, 18 weeks, similar at 36) – Prozac + CBT (widely studied) – Sertraline + CBT or interpersonal psychotherapy – Adolescents- Lexapro • Therapy-improving adaptive behaviors and coping skills, family and peer relationships, and self-esteem (therapeutic alliance) First line • For children and adolescents with acute depressive disorders, first line pharmacotherapy is Fluoxetine. • There is more consistent, high quality evidence for the efficacy of fluoxetine than other antidepressants Why choose another medication • Desire to avoid specific adverse effects • Response to a different antidepressant during a prior depressive episode • Response to a different antidepressant by parent or sibling • Known hypersensitivity to fluoxetine in the patient or family • Patient and/or family preference • Potential drug-drug interactions Other options • • • • Sertraline (Zoloft) Lexapro (escitalopram) Celexa (citalopram) Then – Venlafaxine, Bupropion, Cymbalta • Lack of benefit – Paxil, Tricyclics Alternative treatments • Anti-inflammatory – Fish oil, probiotics • Antioxidants/NRF2 activators – N-Acetyl cysteine, Alpha lipoic acid, Sulfurophane, Green tea extract, Curcumin • St. John’s Wort/ SAMe Maintenance • 6-12 months Adverse Effects-SSRI’s • Abdominal pain • Agitation, jitteriness, or akathisia (restlessness and inability to sit still) • Diarrhea • Headache • Nausea • Sleep changes • Cardiac events- very rare, qtc prolongation, with lexapro, escitalopram • Serotonin syndrome • Suicidality (black box warning) • Discontinuation syndrome Adverse effects Black box Warning Impact • Rates of depression diagnosed decreased • Decrease in antidepressant prescriptions • Suicide rates were decreasing since the 80’s then… • 2004-2005-largest increase in suicide rates after black box warning implemented • Suicide has continued to decline in pt’s age 60+ Treatment Resistance • • • • • • Adequate dose titration No response 6-12 weeks Bipolar depression Substance use Non adherence (side effects) Stressors – Bullying, abuse, family conflict, peer conflict Treatment Resistance-TORDIA study • Failed SSRI – Switch to another SSRI – Or SNRI (venlafaxine, Cymbalta) potentially more side effects – Add psychotherapy • Off label meds – ECT (rarely used in adolescents) Adjunctive treatment • • • • • • Second generation antipsychotics (Abilify) Buspar Thyroid hormone Stimulants Bupropion Trazodone, Remeron (more commonly used for sleep, appetite) Looking toward the future • Fast acting antidepressants that work through glutamate, ketamine and derivatives • Subutex and Ketamine for suicidal ideation • rTranscranial Magnetic Stimulation • Optogenetics- triggering nerves by light • Psychedelics- NYU, Johns Hopkins- Psilocybin trials • UTHNE- fibrinolysis and depression Thanks references • • • • • • • • • • • Uptodate.com: Essau C, Dobson K. Epidemiology of depressive disorders. In: Essau C, Petermann F, eds. Depressive Disorders in Children and Adolescents: Epidemiology, Course and Treatment. Northvale, NJ: Jason Aronson Inc; 1999:69-103 US Food and Drug Administrtion. Background on suicidality associated with antidepressant drug treatment. Available at: www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-04-Tab02-Laughren-Jan5.pdf (Accessed on March 24, 2008). Ambrosini PJ. A review of pharmacotherapy of major depression in children and adolescents. Psychiatr Serv 2000; 51:627. Hetrick SE, McKenzie JE, Cox GR, et al. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev 2012; 11:CD004851. Emslie GJ, Rush AJ, Weinberg WA, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997; 54:1031. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163:1905. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289:3095. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013. Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry 2005; 66 Suppl 8:5. Rush AJ, Warden D, Wisniewski SR, et al. STAR*D: revising conventional wisdom. CNS Drugs 2009; 23:627.