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    Dec.18.2023

    Depression in Adolescents

    Summary

    Key Points

    • Routine screening, with a validated tool if available, for depression in adolescents is recommended annually
      • US Preventive Services Task Force recommends screening for MDD (major depressive disorder) in adolescents aged 12 to 18 years6
      • American Academy of Pediatrics recommends that adolescent patients aged 12 years and older be screened annually for MDD with a formal screening tool such as the PHQ (Patient Health Questionnaire) or the Patient Health Questionnaire for Adolescents3,6,7,8
    • Clinical interview should be utilized to assess for depressive symptoms
    • Based on the severity of symptoms, clinicians can treat patients with antidepressants, or refer to mental health specialists for ongoing treatment (with/without medications and/or therapy)
    • Evaluate for suicide risk by performing a standardized suicide risk screen in adolescent patients struggling with depression and follow a positive screen with a Brief Suicide Safety Assessment18,20
    • Work with patients, families, and mental health partners to develop safety plans for patients struggling with suicidal thoughts18,20

    Alarm Signs and Symptoms

    • Common warning signs may include, but are not limited to:18
      • Talking about killing oneself, feeling hopeless, feeling like a burden, or having no reason to live
      • Mood changes, including depression, anxiety, and agitation
      • Behavior changes:
        • Increased substance use
        • Withdrawing from activities
        • Isolating from family and friends
        • Sleeping too much or not enough
        • Giving away prized possessions
        • Irritability

    Basic Information

    Background Information

    • MDD (major depressive disorder) in adolescents is a serious psychiatric illness with extensive morbidity and mortality that remains underdiagnosed before adulthood1

    Epidemiology

    • Between 2013 and 2019, one-fifth (20.9%) of children and adolescents aged 12 to 17 years surveyed reported a prior major depressive episode2
    • MDD in children and adolescents is associated with recurrent depression in adulthood, other mental health disorders, an increased risk for suicidal ideation, suicide attempts, and death by suicide3
    • Suicide is the second-leading cause of death among children and adolescents aged 10 to 19 years3

    Etiology and Risk Factors

    Etiology

    • Monoamine-deficiency theory states that the pathophysiologic etiology of depression is a depletion of neurotransmitters including serotonin, norepinephrine, or dopamine4
    • Many antidepressants target the monoamine systems4

    Risk Factors

    • Genetic factors can put adolescents at higher risk of developing depression5
    • Social-environmental factors can have significant contributions to depression risk in adolescents (eg, adverse childhood experiences, traumatic family events, poverty, and racial/ethnic and other forms of discrimination)1,5

    Diagnosis

    Approach to Diagnosis

    • Clinicians should combine depression-specific screening tools and patient interviews to arrive at an accurate diagnosis3
    • Screening
      • Screening is the first step in making a diagnosis of depression3
      • Early identification of depression in adolescent patients can guide early intervention, treatment, and self-management skills5
      • Most commonly used screening test in clinical practice is the PHQ (Patient Health Questionnaire)6,7
      • Patient Health Questionnaire for Adolescents is a validated screening tool specifically designed for adolescent patients8
    • Assessment
      • A high score on a screening tool alone does not make for a diagnosis of MDD3
      • Initial presentation of depressive disorders may be variable
        • Symptoms may include sad or irritable mood, feelings of emptiness or boredom, somatic complaints, fatigue, social withdrawal, declining school performance, familial conflict, or a decline in self-care3,5
      • A commonly used mnemonic for symptoms of MDD is "SIGECAPS"9
        • Sleep disorder (either increased or decreased sleep)
        • Interest deficit (anhedonia)
        • Guilt (worthlessness, hopelessness, regret)
        • Energy deficit
        • Concentration deficit
        • Appetite disorder (either decreased or increased)
        • Psychomotor retardation or agitation
        • Suicidality

    Diagnostic Criteria

    • MDD is characterized by a discrete episode lasting at least 2 weeks in duration involving clear changes in mood, interest/pleasure, cognition, and neurovegetative functions5,10,11
      • Symptoms must be present for most of the day, nearly every day, and must result in clinically significant distress or functional impairment5,10,11
      • Five (or more) of the following symptoms have been present during the same 2- week period and represent a change from prior functioning5,10,11 These symptoms correspond to the PHQ7
        • At least 1 of the symptoms is either:
          • Depressed mood or irritable mood
          • Loss of interest of pleasure or anhedonia
          • Changes in appetite or weight
          • Insomnia or hypersomnia
          • Psychomotor agitation or retardation (observed)
          • Fatigue or loss of energy
          • Feelings of worthlessness, excessive feelings of guilt
          • Impaired decisiveness or concentration
          • Recurrent thought about death, dying, suicidal ideation or attempt
      • Alternative medical, substance, or psychiatric explanations, hypomanic/manic episodes must be ruled out5,10,11

    Workup

    History

    • Clinicians should interview the adolescent privately; however, it is important to remind patients that safety concerns (related to suicidal ideation) take precedence over confidentiality12
      • Adolescents should be informed of this before the interview12
    • Evaluate for risk factors: personal or family history of mental health diagnoses, suicide-related behaviors, substance use, significant psychosocial stressors, and/or trauma history3

    Physical Examination

    • Elements of the mental status exam, including general appearance (ie, self-care, hygiene), speech, mood and affect, thought process, thought content, perceptual disturbances (ie, hallucinations), sensorium and cognition, insight, and judgment, can help to rule in/out specific psychiatric or neurologic disorders13,14

    Differential Diagnosis

    • Table 1. Differential Diagnosis: Depression in adolescents.11ADHD, attention-deficit/hyperactivity disorder; MDD, major depressive disorder.Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association; 2013.
      ConditionDescriptionDifferentiated by
      Manic episodes with irritable moodIrritable mood can be found with MDD and manic episodesManic symptoms may be more variable and change rapidly
      Mood disorder due to another medical conditionMood issues can arise from a specific medical condition (eg, multiple sclerosis, stroke, hypothyroidism, diabetes)Assess for other medical issues during clinical interview
      Substance/medication-induced depressive or bipolar disorderSubstance (eg, drug of abuse, medication, toxin) appears to be related to mood disturbanceAssess for exposure to substances
      ADHDDistractibility and low-frustration tolerance can occur with MDD and ADHD; ADHD and MDD may co-occurPerform formal screening for ADHD
      Adjustment disorder with depressed moodAdjustment disorder occurs in response to a psychosocial stressorFull criteria for MDD are not met in adjustment disorder
      SadnessSadness is an inherent aspect of the human experienceFull criteria for MDD are not met with sadness
      Premenstrual dysphoric disorderAssociated with symptoms before menses onset, resolve shortly after mensesDepressive symptoms associated with menses
      Seasonal affective disorderAssociated with symptoms during fall and winter months with less sunlightSymptoms typically improve in the spring
      Disruptive mood dysregulation disorderAssociated with frequent and severe temper outburstsSignificant outbursts, anger, irritability
      Bipolar disorderDepression and mania/hypomania symptomsManic/hypomanic episodes

    Treatment

    Approach to Treatment

    • Appropriate treatment depends on symptoms and symptom severity (Figure 1)
    • For patients with mild depressive symptoms:
      • Provide active support to patients and families for 6 to 8 weeks, checking in every 1 to 2 weeks15
      • If symptoms resolve, continue routine follow-up and screening15
      • If symptoms worsen, consider more active intervention (medication, psychotherapy, and/or referral)15
    • For patients with moderate depressive symptoms:
      • Consider referral to mental health specialist or manage within primary care15
      • If managing within primary care: initiate medication and/or therapy15
      • If partially improved after 6 to 8 weeks: consider adding medication (if not already done), increasing to max dose, adding therapy if not done already, consulting with mental health specialist15
      • If not improved after 6 to 8 weeks: reassess diagnosis15
        • Same steps as above (see "If partially improved")
    • For patients with severe depressive symptoms or significant comorbidities:
      • Consider consultation by a mental health specialist15

    Nondrug and Supportive Care

    • Familial involvement is necessary for all phases of depression management3
    • Cultural factors should be considered when working with patients with depression3,16
    • Options for MDD (major depressive disorder) treatment in adolescents include psychotherapy, collaborative care, psychosocial support interventions, and complementary and alternative medicine techniques3
    • Sleep hygiene, proper nutrition, and physical exercise can be important elements of overall wellness in adolescents15
    • Maintain contact with mental health specialist if patient continues with therapy15

    Drug Therapy

    • Antidepressants with or without other forms of therapy are an effective treatment for depression in adolescents15
    • Fluoxetine is FDA approved for use in children and adolescents aged 8 years and older with MDD15
    • Escitalopram is FDA approved for use in adolescents aged 12 years and older with MDD15
    • Sertraline is FDA approved for use in children and adolescents with obsessive-compulsive disorder, but has been shown to be safe and effective in the treatment of MDD in children and adolescents17
    • Adolescents should have some clinical response at 2 to 3 weeks of therapeutic dose15
      • If a response is not noted at this time, increase the dose15
      • If a response is seen, continue for 4 to 6 weeks and reassess dose15
    • Table 2. SSRI titration schedule for the treatment of MDD in adolescents.15SSRI, selective serotonin reuptake inhibitor.*These medications are contraindicated with concurrent use with monoamine oxidase inhibitors.Data from Cheung AH et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC). Treatment and ongoing management. Pediatrics 2018;141(3):e20174082.
      Medication*Starting dose (every day)IncrementsEffective doseMaximum dosage
      Fluoxetine5 to 10 mg10 to 20 mg20 mg60 mg
      Sertraline25 mg12.5 to 25 mg50 mg200 mg
      Escitalopram5 to 10 mg5 mg10 mg20 mg

    Follow-up

    Monitoring

    • All antidepressants have an FDA black-box warning for children and adolescents stating that pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases15
    • After initiating treatment with medications, patients should be evaluated within 1 week to assess for presence of or increasing suicidal thoughts15
    • While titrating the medication dosage, patients should be monitored every 1 to 2 weeks15
      • Assess for depressive symptoms, suicidality, and potential adverse effects from treatment15
      • Common mild side effects include dry mouth, constipation/diarrhea, irritability, disinhibition, headache, appetite change15
      • More serious side effects may include akathisia, serotonin syndrome, hypomania15
      • If side effects are mild, wait 2 to 7 days to see if symptoms are transient or tolerable15
      • If side effects are moderate, reduce or change the dosing schedule15
      • If side effects are severe, discontinue therapy15
    • If symptoms are improved after 6 to 8 weeks of treatment, monitor with regular follow-up monthly for 6 months postsymptom resolution, and continue medication for a year after full resolution of symptoms15

    Complications

    • Suicide risk can occur at any phase of screening, assessment, and treatment for depression15
    • Engage in open discussion with patients and families around suicide, implement suicide risk screening, and include safety planning in management plans12,15,18

    Prognosis

    • Recovery rates for MDD (major depressive disorder) in adolescents are high, though recurrence is possible in the years following initial treatment19
    Forkey H et al. Trauma-informed care. Pediatrics. 2021;148(2):e2021052580.34312292https://doi.org/10.1542/peds.2021-052580Bitsko RH et al. Mental health surveillance among children — United States, 2013-2019. MMWR Suppl. 2022;71(2):1-42.35202359https://doi.org/10.15585/mmwr.su7102a1Zuckerbrot RA et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation, Identification, Assessment, and Initial Management. Pediatrics. 2018;141(3):e20174081.29483200https://doi.org/10.1542/peds.2017-4081Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry. 2010;9(3):155-161.20975857https://doi.org/10.1002/j.2051-5545.2010.tb00298.xWalter HJ et al. Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents With Major and Persistent Depressive Disorders. J Am Acad Child Adolesc Psychiatry. 2023;62(5):479-502.36273673https://doi.org/10.1016/j.jaac.2022.10.001US Preventive Services Task Force (USPSTF) et al. Screening for Depression and Suicide Risk in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;328(15):1534-1542.36219440https://doi.org/10.1001/jama.2022.16946Kroenke K et al. The PHQ-9. J Gen Intern Med. 2001;16(9):606-613.11556941https://doi.org/10.1046/j.1525-1497.2001.016009606.xJohnson JG et al. The patient health questionnaire for adolescents. J Adolesc Health. 2002;30(3):196-204.11869927https://doi.org/10.1016/S1054-139X(01)00333-0Carlat DJ. The psychiatric review of symptoms: a screening tool for family physicians. Am Fam Physician. 1998;58(7):1617-1624.9824959Uher R et al. Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. Depress Anxiety. 2014;31(6):459-471.24272961https://doi.org/10.1002/da.22217American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association; 2013.Shain B et al. Suicide and suicide attempts in adolescents. Pediatrics. 2016;138(1):e20161420.27354459https://doi.org/10.1542/peds.2016-1420Snyderman D et al. Mental status exam in primary care: a review. Am Fam Physician. 2009;80(8):809-814.19835342King RA. Practice parameters for the psychiatric assessment of children and adolescents. J Am Acad Child Adolesc Psychiatry. 1997;36(10):4S-20S.9606102https://doi.org/10.1097/00004583-199710001-00002Cheung AH et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management. Pediatrics. 2018;141(3):e20174082.29483201https://doi.org/10.1542/peds.2017-4082Cauce AM et al. Cultural and contextual influences in mental health help seeking: a focus on ethnic minority youth. J Consult Clin Psychol. 2002;70(1):44-55.11860055https://doi.org/10.1037/0022-006X.70.1.44Wagner KD et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA. 2003;290(8):1033-1041.12941675https://doi.org/10.1001/jama.290.8.1033American Academy of Pediatrics (AAP). Suicide: Blueprint for Youth Suicide Prevention. AAP website. 2023. Accessed August 28, 2023.https://www.aap.org/en/patient-care/blueprint-for-youth-suicide-prevention/Curry J et al. Recovery and recurrence following treatment for adolescent major depression. Arch Gen Psychiatry. 2011;68(3):263-269.21041606https://doi.org/10.1001/archgenpsychiatry.2010.150Aguinaldo LD et al. Validation of the ask suicide-screening questions (ASQ) with youth in outpatient specialty and primary care clinics. Gen Hosp Psychiatry. 2021;68:52-58.33310014https://doi.org/10.1016/j.genhosppsych.2020.11.006
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