Depression

Description

Other Names

Major depressive disorder (MDD)

Diagnosis Coding

ICD-10

F32.x, Major depressive disorder, single episode

F33.xx, Major depressive disorder, recurrent episode

F32.8, Other specified depressive disorder

F32.9, Unspecified depressive disorder

F34.1, Persistent depressive disorder (formerly dysthymia)

F34.8, Disruptive mood dysregulation disorder

F43.21, Adjustment disorder with depressed mood

F43.23, Adjustment disorder with mixed anxious and depressed mood

N94.3, Premenstrual dysphoric disorder

For major depressive disorder, a 4th digit, indicated by x, is required. For recurrent episodes, a 5th digit may be required to indicate severity/status. For coding details, see ICD-10 for Depressive/Mood Disorders, ICD-10 for Adjustment Disorders, or the Diagnostic and Statistical Manual of Mental Disorders, DSM-5 [American: 2013].

Description

Depression is common and affects up to 11.7% of youth by age 18. [Merikangas: 2010] A major depressive disorder (MDD) is diagnosed when a child or adolescent has a distinct change in mood and becomes persistently depressed or irritable and/or experiences a loss of interest or pleasure for at least 2 weeks. The change in mood affects social or school/occupational functioning.

Criteria for the diagnosis of major depression outlined in the DSM-5 [American: 2013] require symptoms that include 5 or more of the following: depressed mood, loss of interest or pleasure, sleep disturbance, appetite or weight disturbance, low energy, psychomotor disturbance, poor concentration, guilt or shame, and suicidal thoughts or behavior.

Depressive disorders are characterized by sad, empty, or irritable mood and accompanied by somatic and cognitive changes that significantly affect the individual’s capacity to function The various disorders differ primarily by timing, duration, and etiology. Depressive disorders are classified as MDD, disruptive mood dysregulation disorder, persistent depressive disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, and other specified or unspecified depressive disorders. [American: 2013] This module will focus on MDD in children.

Prevalence

The prevalence of depressive disorders is about 2% in prepubertal children and 6% in post-pubertal adolescents. In prepubertal children, males and females are equally affected; after puberty, rates of depression are twice as high in females. [Birmaher: 2007] Prospective studies of childhood depression show stable prevalence over time. [Merikangas: 2009]

Genetics

Though multiple studies support a genetic component to depression, candidate genes are not well defined and a multifactorial etiology, which may include environmental factors, is hypothesized. [Flint: 2014] [Kupfer: 2012]

Prognosis

Up to 70% of affected youths experience recurrence of major depression within 5 years of an episode. [Birmaher: 2007] The likelihood of subsequent recurrence increases with each episode.

Roles Of The Medical Home

Primary care pediatric clinicians are often the first-line in evaluation AND successful treatment of depressive disorders. Failure to improve with adequate treatment trials is a criterion for consultation with, or referral to, a qualified child and adolescent psychiatrist see all Psychiatrist, Child-18 (MD) services providers (24) in our database .

Practice Guidelines

Zuckerbrot RA, Cheung A, Jensen PS, Stein REK, Laraque D.
Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation, Identification, Assessment, and Initial Management.
Pediatrics. 2018. PubMed abstract

Cheung AH, Zuckerbrot RA, Jensen PS, Laraque D, Stein REK.
Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management.
Pediatrics. 2018. PubMed abstract

Helpful Articles

PubMed search for depression in children and adolescents, last two years

Cheung AH, Kozloff N, Sacks D.
Pediatric depression: an evidence-based update on treatment interventions.
Curr Psychiatry Rep. 2013;15(8):381. PubMed abstract / Full Text

David-Ferdon C, Kaslow NJ.
Evidence-based psychosocial treatments for child and adolescent depression.
J Clin Child Adolesc Psychol. 2008;37(1):62-104. PubMed abstract

Maalouf FT, Brent DA.
Child and adolescent depression intervention overview: what works, for whom and how well?.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):299-312, viii. PubMed abstract

March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J.
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.
JAMA. 2004;292(7):807-20. PubMed abstract

Wren FJ, Foy JM, Ibeziako PI.
Primary care management of child & adolescent depressive disorders.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):401-19, ix-x. PubMed abstract

Clinical Assessment

Overview

Lacking a reliable laboratory test or universal approach to evaluation, the diagnosis of depressive disorders is defined by somewhat complex criteria that describes the types of depression and guides the treatment and understanding of the expected clinical course and outcome.

Pearls & Alerts

Suicidality

Assessment for depression must ALWAYS include assessment of current and past suicidality. If a patient is expressing suicidal thoughts, measures must be taken immediately to ensure safety. Please see Suicidality.

Depression and anxiety

The incidence of depression in children and youth with anxiety is up to 4-fold that of other children. Anxiety generally precedes the onset of depression, so carefully assess youth with anxiety for symptoms of depression.

SIGECAPS

This is a mnemonic for the symptoms of depression (save for the first symptom of depressed mood):

  • S – sleep
  • I – interest
  • G – guilt
  • E – energy
  • C – concentration
  • A – appetite or weight
  • P – psychomotor changes
  • S - suicidality

The interview

When assessing youth with depressive symptoms, it is important to interview the patient apart from the parents or caregivers for at least a portion of the visit; often, it is uncomfortable for the patient to discuss the symptoms or related life stressors with caregivers there. That said, it is equally important to speak to parents about the symptoms, current level of functioning, and past history.

Sub-threshold symptoms

Youth with sub-threshold depressive symptoms (symptoms inadequate in duration or number to qualify for a specific diagnosis) are at increased risk for developing MDD and should be carefully monitored and assessed for its development.

Screening

For The Condition

The United States Preventive Services Task Force (USPSTF) recommends universal screening for depression in adolescents 12-18 years old. [Siu: 2016] Insufficient evidence exists to recommend universal screening for children 11 years old and younger. [Siu: 2016]

The following validated tools may be used for screening. They may also be used in at-risk populations, to follow and quantify changes in depression severity over time, and in response to treatment.

Of Family Members

Parental depression leads to an increased risk of mood and behavior problems in children. The American Academy of Pediatrics (AAP) recommends screening all mothers for maternal depression at well-child visits until the child is 4 months of age. The Edinburgh Postnatal Depression Scale (English) (PDF Document 120 KB) is often used in pediatric settings. The Portal has more information at Maternal Depression Screening.

The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. [Siu: 2016] Referral to parents’ primary care clinician for screening or using the Center for Epidemiological Studies Depression Scale for Children (CES-DC) (PDF Document 37 KB) in the pediatric setting may be appropriate.

Presentations

See Depression through Childhood Development for the common presentations of depression at various developmental stages.

Diagnostic Criteria

The following criteria are based on the Diagnostic and Statistical Manual of Mental Disorders 5th Ed. (DSM-5) [American: 2013]; permission to quote the criteria directly was denied.

Depressive disorders in children and adolescents:
  • Major depressive disorder (MDD) consists of 1 or more major depressive episodes (2 weeks or more of the symptoms described above). If mania or hypomania is present or has been present in the past, MDD cannot be diagnosed (thus, bipolar disorder excludes MDD).
  • Persistent depressive disorder consists of depressed mood on most days for at least 1 year in children (2 years in adults). Persistent depressive disorder may be less severe than MDD in overall number of symptoms but, due to its chronicity, it can result in greater dysfunction in social and school/occupational areas.
  • Premenstrual dysphoric disorder (PMDD) consists of symptoms presenting in the week before the onset of menses, including 1 or more of the following: depressed mood, anxiety, irritability, or mood swings combined with 1 or more of the following (for a total of 5 symptoms): loss of interest, poor concentration, low energy, appetite change, sleep disturbance, feeling overwhelmed, or physical symptoms.
  • Disruptive mood dysregulation disorder (DMDD) is a new diagnosis meant to address the population of youth experiencing severe, chronic, non-episodic irritability with outbursts. It consists of severe, frequent (>3 times weekly), recurrent outbursts, inconsistent with developmental level and with persistent irritable or angry mood between outbursts over at least 12 months. If mania or hypomania has been present in the past, DMDD cannot be diagnosed (bipolar disorder excludes DMDD).
  • Other specified depressive disorder, or unspecified depressive disorder may be diagnosed in situations when a patient has depressed mood but does not meet full symptom or duration criteria for MDD or persistent depressive disorder.
“Sub-syndromal” symptoms of depression (i.e., symptoms that do not meet the threshold for diagnosis of MDD) are associated with a 4-5 fold increased risk for subsequent onset of a depressive disorder. [Fergusson: 2005] Certain symptoms (e.g., sad mood, irritability, low motivation) are of greater concern than others (e.g., appetite or weight disturbance, poor concentration) with regard to this increase in risk.

Bipolar depression is characterized by the presence of all of the symptom criteria for MDD and a history of mania or hypomania. Bipolar disorder often presents with symptoms of depression and is important to consider when evaluating a patient for a suspected depressive disorder. Many aspects of diagnosis and treatment of bipolar disorder are distinct from those of other depressive disorders.

Differential Diagnosis

An array of psychiatric disorders share symptoms with depressive disorders.

Bipolar disorder may present with depressive symptoms. ALL of the symptoms of depression can be present in patients with bipolar disorder, in which patients alternate between depression and elevated mood states known as mania or hypomania. Diagnostic criteria for bipolar disorder in adults are well established, but there is controversy over their application in children and adolescents. Many aspects of treatment of bipolar disorder are distinct from those of other depressive disorders. Referral to a child and adolescent psychiatrist for diagnostic confirmation is appropriate.

Anxiety disorders may present with low self-esteem, worthlessness, apparent lack of motivation (often anxiety-based avoidance rather than true low motivation), sleep disturbance (insomnia is common as the patient lies awake worrying), eating problems (decreased appetite or eating rituals), and/or poor concentration. Eliciting specific mood symptoms (sadness, irritability) is important in differentiating these diagnoses. See Anxiety Disorders, Initial Diagnosis for assessment information.

Disruptive behavior disorders/ADHD may present with poor concentration, low self-esteem, and feelings of worthlessness due to social and academic difficulties.

Anorexia nervosa often presents with depressed or irritable mood, low motivation, and low energy, in addition to decreased food intake and weight loss.

Adjustment disorder with depressed mood consists of depressed mood and impaired function within 3 months of a clearly defined stressful life event. To be diagnosed with an adjustment disorder, the patient cannot meet full criteria for a major depressive episode.

Comorbid Conditions

The most common psychiatric comorbidities in youth with depression include anxiety disorders, ADHD, Oppositional Defiant Disorder, and substance use disorders.

History & Examination

Family History

Family history is helpful in evaluation – depressive disorders have a well-demonstrated genetic component. A full psychiatric family history should include family history of depression, suicide attempts and completed suicide, psychiatric hospitalizations, bipolar disorder, anxiety disorders, substance use disorders, ADHD, learning disorders, and schizophrenia.

Pregnancy Or Perinatal History

There is growing interest in the relationship of perinatal factors, such as low birth weight, with depression in later life but conclusive data is lacking.

Current And Past Medical History

The history should address symptoms of depression that overlap with those of medical illness (e.g., insomnia, hypersomnia, low energy, appetite changes, and weight changes) and symptoms that might indicate an underlying medical cause for depression.

An up-to-date history of medication use and current medications, including herbal medications (particularly St. John's Wort), dietary supplements, and OTC medications, is important, especially if medication therapy for depression is a consideration.

Interim History: Asking about depressive symptoms is the first step in ongoing assessment. A stepwise approach may help save time:
  1. Has the patient felt depressed, hopeless, or sad often over the past month, or has she/he felt less interest in or enjoyment of usual activities often over the past month. Depression and diminished interest (aka anhedonia) are cardinal symptoms of depression – one or the other must be present for diagnosis.
  2. Positive replies should prompt further questioning. The combination of either depressed mood or diminished interest in usual activities, along with 4 of the following symptoms fulfills criteria for major depression:
    • Changes in sleep
    • Feelings of guilt or worthlessness
    • Low energy
    • Poor concentration
    • Appetite or weight change
    • Psychomotor slowing or agitation
    • Suicidal thoughts or gestures
  3. See the above Pearl, SIGECAPS mnemonic for depressive symptoms. Gather information from both the child/adolescent and a guardian. Most child/adolescent mental health professionals agree that adding together symptoms from these separate reports is sufficient for diagnosis of depression. Symptoms must cause significant distress or dysfunction to meet criteria – ask about the impact on school, home, and social areas/activities. Because children may not report symptoms clearly, assessment of changes in behavior or function may provide the best clues.
Use of a validated screening tool (see “Screening” above) is up to the clinician. A screening tool may be administered before a visit to eliminate or reduce the need for the questions outlined in 1 and 2. If depression concerns are uncovered during the routine visit, consider scheduling another visit within a week specifically to address depression and a screening tool could be administered in the interim. If a patient is expressing suicidal thoughts, measures must be taken immediately to ensure safety. See the Related Issue Suicidality.

Developmental And Educational Progress

Always consider the child's developmental level when looking for behaviors and changes in mood that might signal a depressive disorder.

Children and adolescents with developmental delays can also develop depression. The term "dual diagnosis" refers to the combination of intellectual disability and a psychiatric disorder in the same patient.

See the Related Issue page Depression through Childhood Development for more detail.

Social And Family Functioning

Clinically significant distress or impairment in social, occupational, or other important areas of functioning is one of the criteria for diagnosis of a major depressive episode. It is common for children and adolescents with depression to be more withdrawn from family or friends, more irritable, or less interested in normal activities.

Physical Exam

General

A normal physical exam can help to rule out medical illness as a cause for depressive symptoms. Examination is also helpful to address the multiple physical complaints (e.g., abdominal pain) that may accompany depression. If a patient presents with concerns of depression, has had a recent physical exam (within the past 6-12 months), and has no new physical complaints or illnesses upon a review of systems, the physical exam may be deferred at the clinician's discretion to allow more time for interviewing.

Testing

Laboratory Testing

Tests to consider in evaluation for a depressive disorder include TSH to screen for hypothyroidism and urine drug screen to screen for substance use, either of which may complicate or cause depression. A urine pregnancy test should be considered in females to allow for consideration of pregnancy in treatment decisions.

Imaging

Routine use of imaging or EEG in the clinical evaluation of depressive disorders is not recommended. [Luby: 2016]

Genetic Testing

No genetic tests are available to aid in the evaluation of depression. Microarray analysis of cytochrome P450 enzyme gene subtypes, which can identify differences in metabolism of antidepressants, is available but studies to guide clinical use in youth are lacking.

Subspecialist Collaborations & Other Resources

Patients currently expressing active suicidal ideation or who have recently made a suicide attempt should be referred for inpatient psychiatric hospitalization.

Psychiatrist, Child-18 (MD) (see Services below for relevant providers)

May aid in diagnosing depression and related conditions. Due to chronic shortages in the United States, they often see only those patients with the most severe mental illnesses or those with complicating biological, psychological, or social factors. Referral is necessary for patients with suspected bipolar disorder or depression with psychotic features. See also AACAP Guidelines: When to Seek Referral or Consultation with a Child and Adolescent Psychiatrist.

Psychologist, Child-18 (PhD, PsyD) (see Services below for relevant providers)

A clinical child psychologist will have a PhD or PsyD. Clinical or counseling psychologists are adept at evaluating depression and performing diagnostic interviewing or specific testing, such as intelligence or personality testing. They also do therapy, such as cognitive/behavioral therapy and play therapy.

Social Workers (see Services below for relevant providers)

Mental health and substance abuse social workers are the most likely to be involved in evaluating depression. Social workers may interview for assessment, but they usually are not qualified to make a formal mental health diagnosis.

Mental Health Counselor (LPC, LCPC, CMHC) (see Services below for relevant providers)

Other than psychologists and social workers, a number of disciplines may offer interviewing for assessment purposes; however, the clinicians usually are not qualified to make a formal mental health diagnosis. Most often, these counselors hold a master’s degree in Clinical Mental Health Counseling, Marriage and Family Therapy, or Substance Abuse and Behavior Counseling.

Treatment & Management

Overview

The primary treatments for children and adolescents with depressive disorders are medication and psychotherapy. Depression is generally episodic with episodes lasting from months to years. Most episodes are 6-12 months in duration, so it is recommended that treatment be continued for at least 1 year from symptom improvement. The goal of this section is to give a rational and evidence-based overview of widely used treatments.

Pearls & Alerts

Dose and duration of treatment

To achieve full effect, 4 -6 weeks of an adequate dose with adequate adherence is required. This applies to ongoing treatment and management when the clinician should monitor and ensure these factors. When obtaining a report of prior treatment “failures,” assess whether adequate duration, dosage, and adherence were achieved.

Monitoring treatment efficacy

Most of the screening tools listed in this module can also be used to monitor treatment efficacy.

Suicide risk

An independent review of available data by the American Medical Association indicated that “a causal role for antidepressants in increasing suicides in children and adolescents has not been established. ...Concerns that antidepressants potentiate suicidal or self-injurious behavior need to be balanced by the clear risk of suicide in children and adolescents with untreated depression.” [Jane: 2016] Another analysis of all available antidepressant RCTS in youth suggests that antidepressants have benefits that may outweigh these risks. [Bridge: 2007] There is also data demonstrating a correlation between higher rates of SSRI prescriptions and reduction in child and adolescent suicide rates. [Gibbons: 2006]

How should common problems be managed differently in children with Depression ?

Over The Counter Medications

St. John's Wort (hypericum), an herbal remedy sometimes recommended for depression, induces cytochrome P450 3A4, which can result in lowered blood levels of other drugs that are metabolized by that enzyme (e.g., macrolide antibiotics, azole antifungals, benzodiazepines, calcium channel blockers, and calcineurin inhibitors, like cyclosporin and tacrolimus). St. John's Wort also interacts with other antidepressants, such as SSRIs (e.g., fluoxetine, sertraline), SNRIs (e.g., venlafaxine), and MAOIs (e.g., selegeline). If taken along with these antidepressants, it may increase the risk of serotonin syndrome, a serious and potentially fatal drug reaction.

Prescription Medications

Common medications and classes of medications may cause mood changes and therefore need to be monitored closely. Check for interactions.

Systems

Mental Health/Behavior

Treatment should be individualized with the priorities of the patient and family considered; treatment with medication may not be the first choice for all. Psychotherapy alone may be considered for patients with mild to moderate depression. Some of the best evidence has, however, pointed to an advantage for medication over therapy alone. [March: 2004] Patients currently expressing active suicidal ideation or who have recently made a suicide attempt should be referred for inpatient psychiatric hospitalization.

Antidepressant medications include selective serotonin re-uptake inhibitors (SSRI), such as fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and vilazodone, and non-SSRI antidepressants, such as tricyclic antidepressants (TCA), bupropion, venlafaxine, desvenlafaxine, mirtazapine, duloxetine, levomilnacipran, and vortioxetine. Only fluoxetine and escitalopram are FDA approved for use under 18 years of age; use of all other antidepressants is considered “off label” for MDD in children and adolescents.

For details on use of medications to treat depression, as well as a discussion of antidepressants and suicidal adverse events, see Pharmacy& Medications below.

The other major treatment modality is psychotherapy, which refers to any psychology-based treatment directed by a trained mental health professional and delivered by means of communication or behavioral techniques. Psychotherapy is often referred to as ”counseling“ or “talk therapy.” Several types of psychotherapy exist but the only two with significant research evidence for efficacy in the treatment of depressive disorders in children and adolescents are cognitive behavior therapy (CBT) and interpersonal therapy (IPT). See Treatment of Depressive Disorders in Youth: Psychotherapy for further discussion of the different psychotherapy modalities used in children and adolescents.

Subspecialist Collaborations & Other Resources

Psychiatrist, Child-18 (MD) (see Services below for relevant providers)

Referral is necessary for patients with suspected bipolar disorder or depression with psychotic features. Due to chronic shortages in the US, psychiatrists often only see those patients with severe mental illness or complicating biological, psychological, or social factors. Consider referral for depression for patients who:

  • Have no improvement after 6-8 weeks of medications or therapy
  • Require more than 2 psychotropic medications to control symptoms
  • Require psychiatric hospitalization
  • Have parents with significant emotional impairment or substance use issues
  • Have complex psychosocial issues (e.g., history of abuse/neglect, legal problems, poor parental support/supervision, family conflict)
  • Have a family history suggesting adverse reactions to therapy (e.g., planned antidepressant therapy in a patient with family history of bipolar disorder)
  • Are young (≤6 years old)
  • Have chronic medical illness
See also AACAP Guidelines: When to Seek Referral or Consultation with a Child and Adolescent Psychiatrist.

Psychologist, Child-18 (PhD, PsyD) (see Services below for relevant providers)

A clinical child psychologist will have a PhD or PsyD and may provide psychotherapy, but they are generally not trained or permitted to prescribe medications (Louisiana and New Mexico, allow clinical psychologists with special training to prescribe some medications). Many psychologists will, however, consult with prescribers to help coordinate diagnosis and treatment.

Social Workers (see Services below for relevant providers)

Mental Health and Substance Abuse Social Workers, generally with a master’s degrees, are the most apt to be involved in treating depression; they may provide psychotherapy and may consult with other specialists to coordinate treatment.

Mental Health Counselor (LPC, LCPC, CMHC) (see Services below for relevant providers)

Other than psychologists and social workers, a number of disciplines that may provide psychotherapy. Most often, these counselors hold a master’s degree in Clinical Mental Health Counseling, Marriage and Family Therapy, or Substance Abuse and Behavior Counseling. They also do therapy, such as cognitive/behavioral therapy and play therapy.

Pharmacy & Medications

Medications can be effective and serve as the mainstay of treatment for many children with depression but variability in response to any medication and to different medications is substantial. Primary care clinicians may do best by developing experience with a few selected medications and referring patients who don’t respond for more expert care.

General considerations for treatment with any antidepressant include: [Boylan: 2007]
  • Start at low doses and titrate up over several days as tolerated.
  • Patients should have frequent follow-up, preferably weekly until dose is stable and medication is tolerated.
  • A trial at an adequate dose should go on 2-4 weeks before any further dose increase because it may take that long to see any benefit. If there is no beneficial effect after 2-4 weeks, dose may be increased.
  • Antidepressants work best when taken daily at the same time.
  • Most antidepressants with once-a-day dosing can be taken in the morning or evening based upon patient preference and observed side effects.
  • Total trial time should be at least 6-8 weeks. A medication trial should not be considered a failure until the maximum tolerated dose has been used for this long without improvement.
  • Family history of response to a particular medication may be used as an approximate guide for medication selection.
  • The FDA approval of fluoxetine and escitalopram may make those medications appealing choices for clinicians; however, clinical judgment may lead to the use of other medications.
The following is not an exhaustive review and should not be substituted for clinician training and judgment. For full prescribing information, please refer to the manufacturer’s package insert.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the best-studied antidepressant medications for children and adolescents. They also have significant benefit for anxiety disorders including generalized anxiety disorder, panic disorder, and OCD. The effects of SSRIs on anxiety reduction are important given that anxiety disorders are commonly comorbid with depression.

SSRI side effects are usually mild and often transient. Common side effects include headaches, GI upset, somnolence, agitation, and sexual side effects (e.g., decreased libido, anorgasmia).

In both adults and children, SSRIs confer a small risk of serotonin syndrome, which is an adverse reaction and a medical emergency. Symptoms of serotonin syndrome include fever, confusion, and tremor/rigidity. Risk is increased by certain medication interactions. The most significant and dangerous medication interaction for SSRIs is with MAOIs (monoamine oxidase inhibitors – another type of antidepressant which is infrequently used in children). All patients should be questioned about other medications they are taking, including herbal and over-the-counter medications. If serotonin syndrome is suspected, SSRI should be immediately discontinued, and the patient should be referred to an emergency room for hospital admission. Combining SSRIs with any antidepressant including, but not limited to SNRIs, TCAs, and even other SSRIs, increases the risk for serotonin syndrome.

Treatment is supportive:
  • Fluoxetine has the most positive data from controlled trials in children and adolescents with 3 trials demonstrating significant difference from placebo. [March: 2004] [Emslie: 1997] [Emslie: 2002] It has a longer half-life than most other SSRIs (1-4 days) and an active metabolite, norfluoxetine, which has an even longer half-life (7-15 days). This can be a useful pharmacokinetic feature since it is somewhat more forgiving than other SSRIs when doses are missed. However, if a patient has a negative reaction to fluoxetine, the long half-life can extend the duration of the adverse reaction.
    • FDA approved for use in children 8 years and older with MDD and those 7 years and older with obsessive-compulsive disorder
    • Available as brand name (e.g., Prozac) and generic in several formulations, including 10 mg, 20 mg, 40 mg, and 60 mg tablets; 10 mg, 20 mg, and 40 mg capsules; 90 mg delayed release (weekly) capsules; 20 mg/5 ml solution
    • Starting dose for adolescents: 10 to 20mg once daily, initial target dose 20mg once daily, dose range 10mg-60mg once daily
  • Sertraline has 1 positive trial (2 studies, which were combined by study design); however, the significance of the trial results was lessened by a very high placebo response rate (53%). [Wagner: 2003] High placebo response rates are characteristic of all existing trials of antidepressants in children and adolescents.
    • FDA approved for use in children 6 years and older with MDD
    • Available as brand name (e.g., Zoloft) and generic in several formulations, including 25 mg, 50 mg, 100 mg tablets and 20 mg/ml oral concentrate
    • Starting dose for adolescents: 12.5mg to 25mg once daily, initial target dose 50mg once daily, dose range 25mg to 200mg once daily
  • Paroxetine has 1 trial with mixed results [Keller: 2001] and 1 negative trial (unpublished, see [Cheung: 2005]), so the evidence for efficacy is equivocal. Paroxetine also appears to be less well tolerated in children and adolescents in this author’s opinion and has significant discontinuation symptoms (possibly due to short half-life of 20 hours).
    • Not FDA approved for use in children; other SSRIs may be a better choice for children and adolescents.
  • Citalopram has had 2 controlled trials. One had positive results [Wagner: 2004]; the other did not show a significant difference from placebo (unpublished). The non-significant study included inpatients and also had a high dropout rate, which may have made the results difficult to interpret. Citalopram has also been studied in pediatric patients with functional abdominal pain, with a trend toward efficacy. [Roohafza: 2014]
    • Not FDA approved for use in children. In August 2011, the FDA issued a Drug Safety Communication warning of the potential for QT prolongation and Torsades de Pointes in patients taking citalopram at doses higher than 40mg daily and that citalopram should no longer be used at such doses. The FDA also discouraged use of citalopram at any dose in patients with cardiac conditions predisposing to arrhythmia, including congenital long QT syndrome.
    • Available as brand name (e.g., Celexa) and generic in 10 mg, 20 mg, and 40 mg tablets and 10 mg/5 ml oral solution
    • Starting dose for adolescents: 10mg once daily; initial target dose 10mg to 20mg once daily; dose range 10mg to 40mg once daily.
  • Escitalopram is the S-isomer of citalopram. Escitalopram has had 3 controlled trials. One controlled trial in adolescents aged 12 to 17 years had positive results (unpublished data, Forest Laboratories). Two other controlled trials [Wagner: 2006] and unpublished data, Forest Laboratories), did not show significant difference from placebo. Of note, a post-hoc analysis of the data from the published negative study showed a significant difference from placebo for the adolescent age group.
    • FDA approved for treatment of depression in adolescents aged 12 to 17 years (based on the strength of the positive study and data from a study of citalopram)
    • Available as brand name (e.g., Lexapro) and generic in 5 mg, 10 mg, and 20 mg tablets and 5 mg/5 ml oral solution
    • Starting dose for adolescents: 5mg to 10mg once daily, initial target dose 10mg once daily, dose range 10mg to 30mg once daily
  • Tricyclic antidepressants (TCAs) have been available for many years but have been eclipsed by the SSRIs, largely due to SSRIs having fewer side effects and less toxicity. It is important for pediatric clinicians to know that multiple trials of TCAs have failed to show significant benefit compared to placebo for treatment of depression in children and adolescents. A Cochrane review from 2013 supported the same conclusion.
Other Non-SSRI Antidepressants:
  • Bupropion has no controlled studies for depression in children and adolescents. There is 1 open study of bupropion in children with depression and comorbid ADHD that has positive results. [Daviss: 2001] Bupropion is used in adults for depression and smoking cessation. Unlike SSRIs, bupropion has little effect on anxiety. It may be useful in patients with bipolar disorder and depression as it is less likely than other antidepressants to induce mania. There is a small risk of generalized seizures with bupropion, which is higher at doses >300mg daily. Due to increased risk of seizures, bupropion is contraindicated in patients with an active eating disorder.
    • Not FDA approved for use in children
    • Available as brand name (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban) and generic in 75 mg and 100 mg tablets; 100 mg, 150 mg, and 200 mg extended release (12 hour) tablets; 174 mg, 348 mg, and 522 mg extended release (24 hour) tablets (as hydrobromide); and 150 mg, 300 mg, and 450 mg extended release (24 hours) tablets (as hydrochloride)
    • Starting doses in adolescents: bupropion SR 75mg twice daily, initial target dose 100mg twice daily, dose range 75mg to 150mg twice daily; bupropion XL (Wellbutrin XL) starting dose 150mg once daily, initial target dose 150mg to 300mg once daily, dose range 150mg to 450mg once daily.
  • Venlafaxine (Effexor, Effexor XR) is an SNRI (serotonin-norepinephrine reuptake inhibitor) and thus possesses an additional mechanism of action compared with SSRIs. The spectrum of effects of venlafaxine is nonetheless similar to that of the SSRIs. In fact, at lower doses (<225 mg daily), the norepinephrine reuptake action is not present, effectively making venlafaxine an SSRI at these doses. There have been few studies of its use in children and adolescents. Venlafaxine was studied in a large RCT involving patients who continued to have depression despite adequate treatment with one SSRI, and was not significantly better in that context than a second SSRI; there was no placebo arm. [Brent: 2008] One unpublished study and one small, randomized controlled trial did not show significant benefits.[Boylan: 2007]Pooled results of these two studies showed a small benefit for adolescents only. Studies may have been hampered by a high rate of placebo response. Venlafaxine also has significant discontinuation symptoms that may begin within a few hours of a missed dose. For these reasons, venlafaxine is at best a second line medication for children and adolescents with depression.
  • Desvenlafaxine SR (Pristiq) is an SNRI and is a form of the active metabolite of venlafaxine. Desvenlafaxine SR has had 1 controlled trial. [Weihs: 2018] This trial compared desvenlafaxine SR weight-based dosing to fluoxetine and placebo and was non-significant due to improvement in all study arms. Desvenlafaxine SR is therefore not a first-line medication for children and adolescents with depression.
  • Duloxetine (Cymbalta) is an SNRI. Duloxetine has had 2 controlled trials.[Emslie: 2014] [Atkinson: 2014] Both studies compared duloxetine to fluoxetine (as a standard treatment) and placebo. Both studies showed no significant differences between treatments due to improvement in depression in all study arms (duloxetine at both fixed and flexible doses up to 120mg daily, fluoxetine up to 40mg daily, and placebo). Until more positive findings are produced, duloxetine would not be a first-line medication for children and adolescents with depression.
  • Levomilnacipran (Fetzima) is the newest SNRI on the market, approved by FDA for treatment of depression in adults in July 2013. There is a controlled study in progress for adolescents with MDD: Clinical Trials for Levomilnacipran in Adolescents (clinicaltrials.gov).
  • Mirtazapine (Remeron) has multiple actions at the CNS receptor level that may contribute to antidepressant effect. There have been two unpublished trials of mirtazapine for depression in children and adolescents. Neither trial demonstrated significant difference from placebo. As with venlafaxine, this lack of apparent effect may be due to high placebo response rates. Still, mirtazapine would not be a first-line medication choice for children and adolescents with depression.
  • Vilazodone (Viibryd) inhibits serotonin reuptake and modulates serotonin receptors. It was approved by FDA for treatment of depression in adults in January 2011. A controlled study in pediatric MDD focused on adverse effects was completed in October 2018: Clinical Trials Vilazodone in Adolescents (clinicaltrials.com).
  • Vortioxetine (Trintellix) also inhibits serotonin reuptake and modulates serotonin receptors. It was approved by FDA for treatment of depression in adults in September 2013; there have been no controlled studies of the efficacy of vortioxetine in depressed children or adolescents.
Antidepressants and Suicidal Adverse Events (SAEs)
Use of antidepressant medication in children has become a controversial topic ever since the British Medications and Healthcare Regulatory Agency banned the use of all antidepressants except for fluoxetine in patients <18 years of age in the United Kingdom in 2003. This ban was instituted due to concerns about the potential for suicidal thoughts or behavior in patients taking antidepressant medication. Subsequent evaluation by the US FDA led to a black box warning in 2004 for all antidepressants stating that they may increase the risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. The FDA added a similar warning in 2007 for young adults aged 18-24 years.

The FDA did not institute a ban on use of antidepressants in children and adolescents, nor did the agency revoke the approval of fluoxetine for treatment of depression in patients aged 7-18. The warning reflects an increased risk of suicidal thoughts or behaviors only, not an increased risk of completing suicide: No one in the studies evaluated by the FDA completed suicide. For those taking active medication, the risk of suicidal thoughts or behaviors was only 3.9%; while the placebo group was 1.8%. [Hammad: 2006]

An independent review of available data by the American Medical Association indicated that “a causal role for antidepressants in increasing suicides in children and adolescents has not been established. ...Concerns that antidepressants potentiate suicidal or self-injurious behavior need to be balanced by the clear risk of suicide in children and adolescents with untreated depression.” [Jane: 2016] Another analysis of all available antidepressant RCTS in youth suggests that antidepressants have benefits that may outweigh these risks. [Bridge: 2007] There is also data demonstrating a correlation between higher rates of SSRI prescriptions and reduction in child and adolescent suicide rates. [Gibbons: 2006]

Given concerns for SAEs, rational prescribing practices include making patients and parents aware of the safety concerns around antidepressant use. Patients who are started on antidepressant medication should be observed closely for clinical worsening, suicidal thoughts, or unusual changes in behavior. Families and caregivers should be advised to closely observe the patient and to communicate with the prescribing physician. Follow-up should occur within 1 week after a patient is newly started on an antidepressant.

Subspecialist Collaborations & Other Resources

Psychiatrist, Child-18 (MD) (see Services below for relevant providers)

Can be very helpful in guiding and/or managing pharmacologic therapy, particularly for patients who do not respond promptly or well to standard medications.

Questions from Clinicians

Are others in the family at risk for depression?

Depression does have a genetic component; risk of depression in first-degree relatives of a person with depression is about 2 times higher than in the general population.

Is there depression-related research that the family might be interested in?

Please see the section on “Studies and Registries” under Treatment & Management, and also under Resources for good links to information in research.

How long should I treat my patient with depression?

Depression is most commonly episodic. Episodes can last from months to years. The majority of episodes will last from 6 months to one year, so the general recommendation for medications is that they are continued for at least 1 year from symptom improvement. By analogy, therapy should probably continue at least that long.

Once a depressive episode is resolved, what is the chance it will come back?

Depression is most often recurrent. Up to 70% of adolescents with major depression will experience some degree of recurrence within 5 years.

Are antidepressants safe in children and adolescents? I heard that they could cause suicidal thinking.

In about 4% of children and adolescents participating in studies of antidepressants who were taking active medication, some degree of worsening of suicidality occurred. About 2 percent of those taking placebo experienced worsening suicidality. It is important to note that suicidal thoughts are also a symptom of depression, and these studies were not designed primarily to assess for this side effect. Even more important to note is that in over 4000 subjects, there were no (0) completed suicides in these studies. Therefore, this is not a warning about increased risk of completing suicide—it is a warning about increased risk of suicidal thoughts or behaviors. See Suicidality.

My patient’s family does not want to treat their child’s depression with medication, is it okay to just refer them for psychotherapy?

In some cases of mild to moderate depression, psychotherapy alone may be a reasonable treatment option. This decision should be made in collaboration with the family. The positive effects of psychotherapy may take longer to realize than those of medication.

Issues Related to Depression

Resources

Information for Clinicians

Depression Resource Center (AACAP)
Information for clinicians and families, including FAQs, “Facts for Families,” books, videos, practice parameters, research, and getting help for depression; American Academy of Child & Adolescent Psychiatry.

Resources for Primary Care (AACAP)
A resource center for clinicians treating substance use disorders and mental health issues. Includes practice parameters, a guide for integrating mental health care into the medical home, and information about policy and advocacy; American Academy of Child & Adolescent Psychiatry.

Helpful Articles

PubMed search for depression in children and adolescents, last two years

Cheung AH, Kozloff N, Sacks D.
Pediatric depression: an evidence-based update on treatment interventions.
Curr Psychiatry Rep. 2013;15(8):381. PubMed abstract / Full Text

David-Ferdon C, Kaslow NJ.
Evidence-based psychosocial treatments for child and adolescent depression.
J Clin Child Adolesc Psychol. 2008;37(1):62-104. PubMed abstract

Maalouf FT, Brent DA.
Child and adolescent depression intervention overview: what works, for whom and how well?.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):299-312, viii. PubMed abstract

March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J.
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.
JAMA. 2004;292(7):807-20. PubMed abstract

Wren FJ, Foy JM, Ibeziako PI.
Primary care management of child & adolescent depressive disorders.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):401-19, ix-x. PubMed abstract

Clinical Tools

Assessment Tools/Scales

Beck Depression Inventory-II
A self-administered, 21-item, 10-minute screen for depression for ages 13 years and older; available in Spanish or English for purchase.

Center for Epidemiologic Studies - Depression Scale (CES-D) (PDF Document 171 KB)
A free, self-administered, 20-item, 10-minute screen for depression for ages 14 years and older.

Patient Health Questionnaire Screeners
Free screening tools to be used by clinicians to help detect mental health disorders: PHQ, PHQ-9, GAD-7, PHQ-15, PHQ-SADS, Brief PHQ, PHQ-4. All PHQ, GAD-7 screeners and translations are downloadable from this website and no permission is required to reproduce, translate, display, or distribute them.

Toolkits

Bright Futures in Practice: Mental Health—Volume II, Tool Kit
Comprehensive set of tools for clinicians and families; addresses mental health in various pediatric age groups; includes a variety of resources, checklists, intake and assessment forms, and patient education materials.

Information & Support for Families

Family Diagnosis Page

Information on the Web

Children's Mental Health (MHA)
Policy, advocacy, information, and referral to maximize mental health for people of all ages; Mental Health America.

Depression (NAMI)
Explanations of treatment for various mental disorders, including depression, and suggestions for how to help yourself or others who are struggling with mental health issues ; National Alliance on Mental Illness.

Teens & Young Adults (NAMI)
Focused information about adolescent depression, how to find help, and links to a teen mental health forum called Ok2Talk; National Alliance on Mental Illness.

The Depressed Child (AACAP)
Common symptoms of depression in children and teenagers; American Academy of Child and Adolescent Psychiatry.

Child and Adolescent Mental Health (NIMH)
Information about mental health conditions in children and adolescents, including a list of warning signs, featured videos, and health hotlines; National Institute of Mental Health.

Understanding Depression (KidsHealth)
How to recognize depression in children, give support, and seek help.

National & Local Support

National Alliance on Mental Illness (NAMI)
Provides information about mental illnesses, links to state chapters, information about conferences, and links to additional resources.

Services for Patients & Families in New Mexico

Select services for a different state: ID, MT, NV, RI, UT

Clinical Social Worker (LCSW) (MSW)

We currently have no Clinical Social Worker (LCSW) (MSW) service providers listed; search our Services database for related services.

Mental Health Counselor (LPC, LCPC, CMHC)

See all Mental Health Counselor (LPC, LCPC, CMHC) services providers (568) in our database.

Psychiatrist, Child-18 (MD)

See all Psychiatrist, Child-18 (MD) services providers (24) in our database.

Psychologist, Child-18 (PhD, PsyD)

See all Psychologist, Child-18 (PhD, PsyD) services providers (7) in our database.

Social Workers

See all Social Workers services providers (120) in our database.

For other services related to this condition, browse our Services categories or search our database.

Authors & Reviewers

Initial Publication: October 2018; Last Update: October 2018
Current Authors and Reviewers (click on name for bio):
Author: Thomas G. Conover, MD
Reviewer: Jonathan D. Birnkrant, MD
Authoring history
(Limited detail is available on authoring dates before 2014.)
2017: update: Thomas G. Conover, MDA
2013: first version: Thomas G. Conover, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

American Psychiatric Association.
Diagnostic and Statistical Manual of Mental Disorders, DSM-5.
Fifth ed. Arlington, VA: American Psychiatric Association; 2013. 978-0-89042-554-1

Atkinson SD, Prakash A, Zhang Q, Pangallo BA, Bangs ME, Emslie GJ, March JS.
A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder.
J Child Adolesc Psychopharmacol. 2014;24(4):180-9. PubMed abstract

Birmaher B, Brent D, Bernet W, Bukstein O, Walter H, Benson RS, Chrisman A, Farchione T, Greenhill L, Hamilton J, Keable H, Kinlan J, Schoettle U, Stock S, Ptakowski KK, Medicus J.
Practice parameter for the assessment and treatment of children and adolescents with depressive disorders.
J Am Acad Child Adolesc Psychiatry. 2007;46(11):1503-26. PubMed abstract
The most recent practice parameter on the diagnosis and treatment of depressive disorders in children and adolescents. Our prevalence calculation roughly adjusts the cited age-specific prevalences for the age distribution in typical primary care pediatric practice.

Boylan K, Romero S, Birmaher B.
Psychopharmacologic treatment of pediatric major depressive disorder.
Psychopharmacology (Berl). 2007;191(1):27-38. PubMed abstract

Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, Vitiello B, Ritz L, Iyengar S, Abebe K, Birmaher B, Ryan N, Kennard B, Hughes C, DeBar L, McCracken J, Strober M, Suddath R, Spirito A, Leonard H, Melhem N, Porta G, Onorato M, Zelazny J.
Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial.
JAMA. 2008;299(8):901-13. PubMed abstract / Full Text

Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA.
Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials.
JAMA. 2007;297(15):1683-96. PubMed abstract

Cheung AH, Emslie GJ, Mayes TL.
Review of the efficacy and safety of antidepressants in youth depression.
J Child Psychol Psychiatry. 2005;46(7):735-54. PubMed abstract

Cheung AH, Kozloff N, Sacks D.
Pediatric depression: an evidence-based update on treatment interventions.
Curr Psychiatry Rep. 2013;15(8):381. PubMed abstract / Full Text

Cheung AH, Zuckerbrot RA, Jensen PS, Laraque D, Stein REK.
Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management.
Pediatrics. 2018. PubMed abstract

David-Ferdon C, Kaslow NJ.
Evidence-based psychosocial treatments for child and adolescent depression.
J Clin Child Adolesc Psychol. 2008;37(1):62-104. PubMed abstract

Daviss WB, Bentivoglio P, Racusin R, Brown KM, Bostic JQ, Wiley L.
Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression.
J Am Acad Child Adolesc Psychiatry. 2001;40(3):307-14. PubMed abstract

Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, Nilsson M, Jacobson JG.
Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial.
J Am Acad Child Adolesc Psychiatry. 2002;41(10):1205-15. PubMed abstract

Emslie GJ, Prakash A, Zhang Q, Pangallo BA, Bangs ME, March JS.
A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder.
J Child Adolesc Psychopharmacol. 2014;24(4):170-9. PubMed abstract / Full Text

Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J.
A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.
Arch Gen Psychiatry. 1997;54(11):1031-7. PubMed abstract

Fergusson DM, Horwood LJ, Ridder EM, Beautrais AL.
Subthreshold depression in adolescence and mental health outcomes in adulthood.
Arch Gen Psychiatry. 2005;62(1):66-72. PubMed abstract

Flint J, Kendler KS.
The genetics of major depression.
Neuron. 2014;81(3):484-503. PubMed abstract / Full Text

Gibbons RD, Hur K, Bhaumik DK, Mann JJ.
The relationship between antidepressant prescription rates and rate of early adolescent suicide.
Am J Psychiatry. 2006;163(11):1898-904. PubMed abstract

Hammad TA, Laughren T, Racoosin J.
Suicidality in pediatric patients treated with antidepressant drugs.
Arch Gen Psychiatry. 2006;63(3):332-9. PubMed abstract

Jane Garland E, Kutcher S, Virani A, Elbe D.
Update on the Use of SSRIs and SNRIs with Children and Adolescents in Clinical Practice.
J Can Acad Child Adolesc Psychiatry. 2016;25(1):4-10. PubMed abstract / Full Text

Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP.
Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.
J Am Acad Child Adolesc Psychiatry. 2001;40(7):762-72. PubMed abstract

Kupfer DJ, Frank E, Phillips ML.
Major depressive disorder: new clinical, neurobiological, and treatment perspectives.
Lancet. 2012;379(9820):1045-55. PubMed abstract / Full Text

Luby JL, Belden AC, Jackson JJ, Lessov-Schlaggar CN, Harms MP, Tillman R, Botteron K, Whalen D, Barch DM.
Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence.
JAMA Psychiatry. 2016;73(1):31-8. PubMed abstract / Full Text

Maalouf FT, Brent DA.
Child and adolescent depression intervention overview: what works, for whom and how well?.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):299-312, viii. PubMed abstract

March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J.
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.
JAMA. 2004;292(7):807-20. PubMed abstract

Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J.
Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication--Adolescent Supplement (NCS-A).
J Am Acad Child Adolesc Psychiatry. 2010;49(10):980-9. PubMed abstract / Full Text

Merikangas KR, Nakamura EF, Kessler RC.
Epidemiology of mental disorders in children and adolescents.
Dialogues Clin Neurosci. 2009;11(1):7-20. PubMed abstract / Full Text

Roohafza H, Pourmoghaddas Z, Saneian H, Gholamrezaei A.
Citalopram for pediatric functional abdominal pain: a randomized, placebo-controlled trial.
Neurogastroenterol Motil. 2014;26(11):1642-50. PubMed abstract

Siu AL.
Screening for Depression in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.
Pediatrics. 2016;137(3):e20154467. PubMed abstract

Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, Childress A, Donnelly C, Deas D.
Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.
JAMA. 2003;290(8):1033-41. PubMed abstract

Wagner KD, Jonas J, Findling RL, Ventura D, Saikali K.
A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression.
J Am Acad Child Adolesc Psychiatry. 2006;45(3):280-8. PubMed abstract

Wagner KD, Robb AS, Findling RL, Jin J, Gutierrez MM, Heydorn WE.
A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.
Am J Psychiatry. 2004;161(6):1079-83. PubMed abstract

Weihs KL, Murphy W, Abbas R, Chiles D, England RD, Ramaker S, Wajsbrot DB.
Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder.
J Child Adolesc Psychopharmacol. 2018;28(1):36-46. PubMed abstract / Full Text

Wren FJ, Foy JM, Ibeziako PI.
Primary care management of child & adolescent depressive disorders.
Child Adolesc Psychiatr Clin N Am. 2012;21(2):401-19, ix-x. PubMed abstract

Zuckerbrot RA, Cheung A, Jensen PS, Stein REK, Laraque D.
Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation, Identification, Assessment, and Initial Management.
Pediatrics. 2018. PubMed abstract