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* This is the Professional Version. *

Depressive Disorders in Children and Adolescents

By Josephine Elia, MD, Professor of Psychiatry and Human Behavior, Professor of Pediatrics;Attending Physician, Sidney Kimmel Medical College of Thomas Jefferson University;Nemours/A.I. duPont Hospital for Children

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Depressive disorders are characterized by sadness or irritability that is severe or persistent enough to interfere with functioning or cause considerable distress. Diagnosis is by history and examination. Treatment is with antidepressants, supportive and cognitive-behavioral therapy, or both.

(See also discussion of Depressive Disorders in adults.)

Depressive disorders in children and adolescents include

  • Disruptive mood dysregulation disorder

  • Major depressive disorder

  • Persistent depressive disorder (dysthymia)

The term depression is often loosely used to describe the low or discouraged mood that results from disappointment (eg, serious illness) or loss (eg, death of a loved one). However, such low moods, unlike depression, occur in waves that tend to be tied to thoughts or reminders of the triggering event, resolve when circumstances or events improve, may be interspersed with periods of positive emotion and humor, and are not accompanied by pervasive feelings of worthlessness and self-loathing. The low mood usually lasts days rather than weeks or months, and suicidal thoughts and prolonged loss of function are much less likely. Such low moods are more appropriately called demoralization or grief. However, events and stressors that cause demoralization and grief can also precipitate a major depressive episode.

The etiology of depression in children and adolescents is unknown but is similar to etiology in adults; it is believed to result from interactions of genetically determined risk factors and environmental stress (particularly deprivation and loss early in life).

Symptoms and Signs

Basic manifestations of depressive disorders in children and adolescents are similar to those in adults but are related to typical concerns of children, such as schoolwork and play. Children may be unable to explain inner feelings or moods. Depression should be considered when previously well-performing children do poorly in school, withdraw from society, or commit delinquent acts.

In some children with a depressive disorder, the predominant mood is irritability rather than sadness (an important difference between childhood and adult forms). The irritability associated with childhood depression may manifest as overactivity and aggressive, antisocial behavior.

In children with intellectual disability, depressive or other mood disorders may manifest as somatic symptoms and behavioral disturbances.

Disruptive mood dysregulation disorder

Disruptive mood dysregulation disorder involves persistent irritability and frequent episodes of behavior that is very out of control, with onset at age 6 to 10 yr. Many children also have other disorders, particularly oppositional defiant disorder, attention-deficit/hyperactivity disorder (ADHD), or an anxiety disorder. The diagnosis is not made before age 6 yr or after age 18 yr. As adults, patients may develop unipolar (rather than bipolar) depression or an anxiety disorder.

Manifestations include the presence of the following for ≥ 12 mo (with no period of ≥ 3 mo without all of them):

  • Severe recurrent temper outbursts (eg, verbal rage and/or physical aggression toward people or property) that are grossly out of proportion to the situation and that occur ≥ 3 times/wk on average

  • Temper outbursts that are inconsistent with developmental level

  • An irritable, angry mood present every day for most of the day and observed by others (eg, parents, teachers, peers)

The outbursts and angry mood must occur in 2 of 3 settings (at home or school, with peers).

Major depressive disorder

Major depressive disorder is a discrete depressive episode lasting ≥ 2 wk. It occurs in as many as 2% of children and 5% of adolescents. Major depressive disorder can first occur at any age but is more common after puberty. Untreated, major depression may remit in 6 to 12 mo. Risk of recurrence is higher in patients who have severe episodes, who are younger, or who have had multiple episodes. Persistence of even mild depressive symptoms during remission is a strong predictor of recurrence.

For diagnosis, ≥ 1 of the following must be present for most of the day nearly every day during the same 2-wk period:

  • Feeling sad or being observed by others to be sad (eg, tearful) or irritable

  • Loss of interest or pleasure in almost all activities (often expressed as profound boredom)

In addition, ≥ 4 of the following must be present:

  • Decrease in weight (in children, failure to make the expected weight gain) or decrease or increase in appetite

  • Insomnia or hypersomnia

  • Psychomotor agitation or retardation observed by others (not self-reported)

  • Fatigue or loss of energy

  • Decreased ability to think, concentrate, and make choices

  • Recurrent thoughts of death (not just fear of dying) and/or suicidal ideation or plans

  • Feelings of worthlessness (ie, feeling rejected and unloved) or excessive or inappropriate guilt

Major depression in adolescents is a risk factor for academic failure, substance abuse, and suicidal behavior. While depressed, children and adolescents tend to fall far behind academically and lose important peer relationships.

Persistent depressive disorder (dysthymia)

Dysthymia is a persistent depressed or irritable mood that lasts for most of the day for more days than not for ≥ 1 yr plus ≥ 2 of the following:

  • Poor appetite or overeating

  • Insomnia or hypersomnia

  • Low energy or fatigue

  • Low self-esteem

  • Poor concentration

  • Feelings of hopelessness

Symptoms may be more or less intense than those of a major depressive disorder.

A major depressive episode may occur before the onset or during the first year (ie, before the duration criterion is met for persistent depressive disorder).

Diagnosis

  • Clinical evaluation

Diagnosis of depressive disorders is based on symptoms and signs, including the criteria listed above.

Sources of information include an interview with the child or adolescent and information from parents and teachers. Several brief questionnaires are available for screening. They help identify some depressive symptoms but cannot be used alone for diagnosis. Specific close-ended questions help determine whether patients have the symptoms required for diagnosis of major depression, based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.

History should include causative factors such as domestic violence, sexual abuse and exploitation, and drug adverse effects. Questions about suicidal behavior (eg, ideation, gestures, attempts) should be asked.

A careful review of the history and appropriate laboratory tests are needed to exclude other disorders (eg, infectious mononucleosis, thyroid disorders, drug abuse) that can cause similar symptoms.

Other mental disorders that can increase the risk and/or modify the course of depressive symptoms (eg, anxiety, bipolar disorders) must be considered. Some children who eventually develop a bipolar disorder or schizophrenia may present initially with major depression.

After depression is diagnosed, the family and social setting must be evaluated to identify stresses that may have precipitated depression.

Treatment

  • Concurrent measures directed at the family and school

  • For adolescents, usually antidepressants plus psychotherapy

  • For preadolescents, psychotherapy followed, if needed, by antidepressants

Appropriate measures directed at the family and school must accompany direct treatment of the child to enhance continued functioning and provide appropriate educational accommodations. Brief hospitalization may be necessary in acute crises, especially when suicidal behavior is identified.

For adolescents (as for adults), a combination of psychotherapy and antidepressants usually greatly outperforms either modality used alone. For preadolescents, the situation is much less clear. Most clinicians opt for psychotherapy in younger children; however, drugs can be used in younger children (fluoxetine can be used in children 8 yr), especially when depression is severe or has not previously responded to psychotherapy.

Usually, an SSRI (see Table: Drugs for Long-Term Treatment of Anxiety and Related Disorders) is the first choice when an antidepressant is indicated. Children should be closely monitored for the emergence of behavioral side effects (eg, disinhibition, behavioral activation), which are common but are usually mild to moderate. Usually, decreasing the drug dose or changing to a different drug eliminates or reduces these effects. Rarely, such effects are severe (eg, aggressiveness, increased suicidality). Behavioral adverse effects are idiosyncratic and may occur with any antidepressant and at any time during treatment. As a result, children and adolescents taking such drugs must be closely monitored.

Adult-based research has suggested that antidepressants that act on both the serotonergic and adrenergic/dopaminergic systems may be modestly more effective; however, such drugs (eg, duloxetine, venlafaxine, mirtazapine; certain tricyclics, particularly clomipramine) also tend to have more adverse effects. Such drugs may be especially useful in treatment-resistant cases. Nonserotonergic antidepressants such as bupropion and desipramine may also be used with an SSRI to enhance efficacy.

As in adults, relapse and recurrence are common. Children and adolescents should remain in treatment for at least 1 yr after symptoms have remitted. Most experts recommend that children who have experienced 2 episodes of major depression be treated indefinitely.

Drugs for Long-Term Treatment of Anxiety and Related Disorders

Drug

Uses

Starting Dose*

Dose Range

Comments/Precautions

Citalopram

OCD

children ≥ 7 yr

10 mg

10–40 mg/day

Duloxetine

GAD in children 7–17 yr

30 mg

30–100 mg/day

Escitalopram

Major depression in

children ≥ 7 yr

5 mg

5–20 mg/day

Fluoxetine

OCD, GAD, separation anxiety, social anxiety, major depression in children > 8 yr

10 mg

10–60 mg/day

Long-half life

Fluvoxamine

GAD, separation anxiety, social anxiety, OCD in children > 8 yr

25 mg (titrated up as needed)

50–200 mg/day

For doses > 50 mg/day, divided into 2 doses/day,with the larger dose given at bedtime)

Paroxetine

OCD in children > 6 yr

10 mg

10–60 mg/day

Increased weight

Sertraline

OCD, GAD, separation anxiety, social anxiety in children ≥ 6 yr

25 mg

25–200 mg/day

Venlafaxine, immediate-release

Depression in children ≥ 8 yr

12.5 mg

25–75 mg/day bid or tid

Limited data about dose and concerns about increased suicidal behavior; not as effective as other drugs, possibly because low doses have been used

Venlafaxine, extended-release

GAD in children > 7 yr

37.5 mg

37.5–225 mg/day

*Unless otherwise stated, dose is given once/day. Starting dose is increased only if needed. Dose ranges are approximate. Interindividual variability in therapeutic response and adverse effects is considerable. This table is not a substitute for the full prescribing information.

Behavioral adverse effects (eg, disinhibition, agitation) are common but are usually mild to moderate. Usually, decreasing the drug dose or changing to a different drug eliminates or reduces these effects. Rarely, such effects are severe (eg, aggressiveness, increased suicidality). Behavioral adverse effects are idiosyncratic and may occur with any antidepressant and at any time during treatment. As a result, children and adolescents taking such drugs must be closely monitored.

Fluoxetine and paroxetine are potent inhibitors of the liver enzymes that metabolize many other drugs (eg, beta-blockers, clonidine, lidocaine).

GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder.

Suicide risk and antidepressants

Suicide risk and treatment with antidepressants have been a topic of debate and research (1). In 2004, the US FDA did a meta-analysis of 23 previously conducted trials of 9 different antidepressants (2). Although no patients completed suicide in these trials, a small but statistically significant increase in suicidal ideation was noted in children and adolescents taking an antidepressant (about 4% vs about 2%), leading to a black box warning on all classes of antidepressants (eg, tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors such as venlafaxine, tetracyclic antidepressants such as mirtazapine).

In 2006, a meta-analysis (from the United Kingdom) of children and adolescents being treated for depression (3) found that compared with patients taking a placebo, those taking an antidepressant had a small increase in self-harm or suicide-related events (4.8% vs 3.0% of those treated with placebo). However, whether the difference was statistically significant or not varied depending on the type of analysis (fixed-effects analysis or random-effects analysis). There was a nonsignificant trend toward an increase in suicidal ideation (1.2% vs 0.8%), self-harm (3.3% vs 2.6%), and suicide attempts (1.9% vs 1.2%). There appear to have been some differences in risk between different drugs; however, no direct head-to-head studies have been done, and it is difficult to control for severity of depression and other confounding risk factors.

Observational and epidemiologic studies (4, 5) have found no increase in the rate of suicide attempts or completed suicide in patients takings antidepressants. Also, despite a decrease in prescriptions for antidepressants, the suicide rate has increased.

In general, although antidepressants have limited efficacy in children and adolescents, the benefits appear to outweigh risks. The best approach seems to be combining drug treatment with psychotherapy and minimizing risk by closely monitoring treatment.

Whether or not drugs are used, suicide is always a concern in a child or adolescent with depression. The following should be done to reduce risk:

  • Parents and mental health care practitioners should discuss the issues in depth.

  • The child or adolescent should be supervised at an appropriate level.

  • Psychotherapy with regularly scheduled appointments should be included in the treatment plan.

Pearls & Pitfalls

  • Suicide risk is always a concern in children or adolescents with depression whether they are taking antidepressants or not.

Treatment references

  • 1. Hetrick SE, McKenzie JE, Merry SN: Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev Nov 11 2012.

  • 2. US FDA: Review and evaluation of clinical data: Relationship between psychotropic drugs and pediatric suicidality. 2004. Accessed 11/4/16.

  • 3. Dubicka B, Hadley S, Roberts C: Suicidal behaviour in youths with depression treated with new-generation antidepressants: Meta-analysis. Br J Psychiatry Nov 189:393–398, 2006.

  • 4. Adegbite-Adeniyi C, et al: An update on antidepressant use and suicidality in pediatric depression. Expert Opin Pharmacother 13 (15):2119–2130, 2012.

  • 5. Gibbons RD, Brown CH, Hur K, et al: Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry 164 (9);1356–1363, 2007.

Key Points

  • In children, depressive disorders may manifest as sadness or irritability.

  • Major depressive disorder involves feeling sad or irritable or losing interest or pleasure in almost all activities for most of the day nearly every day during a 2-wk period plus other specific symptoms.

  • Diagnose a depressive disorder based on specific clinical criteria, and do appropriate laboratory tests to exclude other disorders (eg, infectious mononucleosis, thyroid disorders, drug abuse).

  • Involve the family and school while treating the child to enhance the child's continued functioning and provide appropriate educational accommodations.

  • For adolescents (as for adults), a combination of psychotherapy and antidepressants usually greatly outperforms either modality used alone; in younger children, most clinicians opt for psychotherapy although if needed, drugs can be used (depending on the child's age).

  • In 2004, the FDA did a meta-analysis that led to a black box warning of a increased risk of suicidal ideation and behavior in children, adolescents, and young adults with all classes of antidepressants; subsequent analyses have cast doubt on this conclusion.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ANAFRANIL
  • NORPRAMIN
  • PAXIL
  • ZOLOFT
  • WELLBUTRIN, ZYBAN
  • XYLOCAINE
  • REMERON
  • CYMBALTA
  • LUVOX
  • EFFEXOR XR
  • CELEXA
  • LEVOPHED
  • PROZAC, SARAFEM
  • LEXAPRO
  • CATAPRES

* This is the Professional Version. *