Don't overlook childhood depression

Lauren L. Louters, PA-C

Ms. Louters is a physician assistant in Denver, Colo. The author has indicated no relationships to disclose relating to the content of this article.

An effective approach to childhood depression requires that you maintain a high index of suspicion and understand the disorder's full spectrum of manifestations.

Although children once were thought to lack the emotional and cognitive ability to experience depressive symptoms, we now know that a range of mood disorders, including major depressive disorder (MDD), can affect children and adolescents. Mood disorders are difficult to detect in children. These disorders have a broad spectrum of presentations, and the child's stage of development, comorbid conditions that may mask or alter depressive symptoms, and the lack of an objective test for mood disorders may complicate diagnosis. The spectrum of normalcy among children may also be a factor: a socially withdrawn 6-year-old may be depressed or may be just shy, while an adolescent's troublesome behavior may be related to clinical depression or to the challenges of growing up.

The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) outlines the criteria for a diagnosis of MDD.¹ The diagnosis can be made only if five or more of the following symptoms are present during the same 2-week period and represent a change from previous functioning:

• Decreased concentration, indecisiveness

• Depressed or irritable mood

• Diminished pleasure or interest in activities

• Failure to make expected weight gains

• Fatigue

• Feelings of guilt or worthlessness

• Insomnia or hypersomnia

• Morbid thoughts, suicidal ideation or attempt

• Psychomotor retardation or agitation.

The symptoms must occur every day or nearly every day and may be reported by the child or an observer such as a parent or a clinician. Symptoms cannot meet criteria for a mixed episode or be attributable to a substance (eg, a medication), general medical condition, or bereavement.¹

The prevalence of depression

The prevalence of MDD is 0.3% to 1% among preschool-age children, 1% to 9% among school-age children, and 4% to 8% among adolescents.^2,3 The prevalence of MDD among adolescents is similar to that among adults, 15% to 20%. Prevalence among boys and girls is approximately equal until adolescence, when the incidence among girls is nearly double that among boys, a disparity that persists throughout adulthood.^2-5

Both genetic and psychosocial factors have a role in depression, and family dysfunction appears to be particularly influential. Other factors include peer problems, chronic illness, prior depressive episodes, and having a first-degree relative with a history of depression (see Table 1).^3-7

 

TABLE 1 Risk factors for childhood depression

Academic difficulties Family dysfunction or caregiver-child conflict Family history of mood disorders, personality disorders, panic disorder, or alcoholism History of anxiety disorders, attention-deficit/hyperactivity disorder, or learning disabilities Low self-esteem, self-consciousness, poor body image Low socioeconomic status Negative style of coping with stress or interpreting events Severe life events such as death of a loved one or abuse Uncertainty regarding sexual orientation

Pathophysiology

Recent research on depression in children has focused on endocrinology, sleep patterns, and neuroimaging. The results of dexamethasone suppression testing, the most extensively studied psychobiological parameter relating to childhood depression, are similar to results found in adults in that children suffering from depression are more than twice as likely to be nonsuppressors. Other research examining the role of growth hormone, thyroid-stimulating hormone, corticotropin-releasing hormone, cortisol, urinary methylhydroxyphenylglycol, immunity indices, and serotonin axis disregulation in depression has been hampered by small sample sizes and contradictory results.^8-10 A small number of sleep studies have also yielded inconsistent results.

Neuroimaging with functional and structural MRI and magnetic resonance spectroscopy has provided the greatest insight into the pathophysiology of depression. MRI comparisons have shown reduced ratios of frontal lobe to cerebral volume. Recent studies also show evidence of diminished amygdala volume. Although subgenual prefrontal cortex gray matter reductions and diminished hippocampal volume have been observed in adults with depression, they have not been demonstrated in children. Magnetic resonance spectroscopy studies have shown an increased ratio of choline to creatinine in the left anterior medial frontal lobe. These promising insights into the neurobiology of depression underscore the need for more research on depression in children.^8-10

Depression is more closely correlated with biological than with adoptive family history.¹¹ As many as 60% of patients with depression who are younger than 20 years have a first-degree relative with a history of depression; a high rate of concordance has been noted among identical twins and in adoption studies.¹¹

History and physical exam

Having a good rapport with the child is essential to obtaining a complete history. Trust, the most important element of a good rapport, may be established by speaking with the child and listening carefully and attentively. Assure older children that unless their safety is at risk, your conversation with them is confidential. Typically, however, the parent or caregiver will present the child's history.

Key information obtained during the history includes the onset, duration, intensity, frequency, severity, and pervasiveness of the symptoms. The child's developmental, social, and family history should also be obtained, along with an account of potential stressors in the child's environment. Depression is often associated with chronic medical conditions and psychological comorbidities, requiring alertness to other medical and psychiatric problems (see Table 2).^2,12

 

TABLE 2 Medical and psychiatric causes of depressive symptoms

Medical Addison's disease Anemia Asthma Diabetes Electrolyte abnormality Epilepsy Hyperkalemia Hyperthyroidism Hypokalemia Lead intoxication Mononucleosis Postconcussion syndrome Systemic lupus erythematosus Vitamin B12 deficiency Wilson's disease Psychiatric Adjustment disorder with depressed mood Anxiety disorder Attention-deficit/hyperactivity disorder Bereavement Bipolar disorder Substance-induced mood disorder

Because children are often unable to identify and appropriately express their emotional experiences, depression manifests itself differently in children than it does in adults, and symptoms typically reflect the child's stage of development (see Table 3). Generally, the depressed child may appear listless, withdrawn, and seemingly unable to find enjoyment in life. Infants and preschoolers may regress or fail to achieve developmental milestones such as toilet training. Younger children are more likely to exhibit separation anxiety, phobias, and somatic complaints. School-age children may resist attending school and have academic problems. Melancholia, psychosis, impaired functioning, and frequency and lethality of suicide attempts increase with age.¹³ The evaluation should of course be conducted within the child's social, intellectual, and developmental framework.

 

TABLE 3 Common manifestations of major depressive disorder by age
Age, y	Common manifestations
<3	Feeding problems, temper tantrums, lack of playfulness and emotional expression
3-5	Phobias, enuresis, encopresis, being accident-prone, being overly apologetic for minor infractions
6-8	Vague somatic complaints (particularly chronic abdominal aches and headaches), aggressive behavior, resistance to new experiences and people
9-12	Excessively morbid thoughts, worry about homework, self-blame
Adolescence	Anger, irritable mood, moodiness, uncommunicativeness, hypersensitivity to criticism, anhedonia, hypersomnia, delinquency, preoccupation with body image

A diagnosis of depression should be made only when other causes of the child's symptoms have been excluded.^2,12 Depending on symptoms and signs elicited from the history and physical exam, appropriate baseline tests may include a CBC with differential, electrolytes, creatinine, BUN, liver function studies, thyroid-stimulating hormone, ECG, MRI, or EEG.¹² Depressive symptoms together with risk factors for a medical problem or with recent head trauma warrant investigation. The absence of risk factors for depression also suggests an underlying organic etiology.

Psychiatric disorders other than MDD—such as bereavement, adjustment disorder with depressed mood, bipolar disorder, and substance-induced mood disorder—should also be considered. Alcohol and marijuana use can cause depressive symptoms, as can drugs such as systemic corticosteroids, oral contraceptives, benzodiazepines, barbiturates, stimulants, and anticonvulsants.¹²

As many as 70% of children who have depression also have at least one other psychiatric comorbidity;¹⁴ typically, these include substance abuse, anxiety disorders, and disruptive disorders (attention-deficit/hyperactivity disorder, oppositional disorder, or conduct disorder).² Depressed children are at increased risk for personality, eating, learning, and somatization disorders. Many of these comorbid conditions mask depression, which can lead to inadequate treatment. Comorbid conditions can affect the severity and recurrence of depressive episodes, treatment response, utilization of mental health services, and suicide attempts.^12,13

Asking the child to rate his or her state of mind on a scale of 1 to 10 may be helpful in the evaluation (where 10 represents always feeling that things are perfect, and 1 is always feeling very upset). In addition, standardized questionnaires developed specifically to aid in the diagnosis of depression in children have been developed. The Beck Depression Inventory, Children's Interview for Psychiatric Syndromes, Diagnostic Interview for Children and Adolescents, Children's Depression Inventory, and other similar tests attempt to utilize language appropriate for a given age group. Having the child's family members, day care workers, and teachers fill out the form may provide further insight. In addition, questionnaires such as the Pediatric Symptom Checklist may be used as routine screening measures during well-child visits.^5,12

Note that a child whose symptoms do not satisfy the DSM-IV-TR criteria for a diagnosis of MDD may still be at risk for impaired functioning. One study of 840 children aged 11 to 15 years and their parents showed that children who had just one or two of the DSM-IV-TR symptoms (compared with the five required for a diagnosis) were more likely to have academic problems than were those who did not show any symptoms.⁷ Evidence that mild forms of depression may lead to more severe forms¹⁵ suggests that practitioners should recognize the potential impairment of these children and follow them closely.

Assessing the risk of suicide

Children and adolescents who are depressed are more likely to experience academic difficulties, social impairment, and somatic complaints than nondepressed children. They are also more likely to engage in risky behaviors, such as substance abuse, smoking, and promiscuity, and have higher rates of attempted and completed suicide. The most worrisome sequelae of childhood depression is suicide, the third leading cause of death among children between 10 and 19 years.¹⁶ The rate of suicide among children younger than 10 years is unavailable.

The single best predictor of suicide attempts is the presence of a psychiatric illness, with depressive syndromes the most common. Comorbidities further increase the risk of suicide. Shaffer and colleagues showed that approximately two thirds of patients who completed suicide had a mood disorder, a substance abuse disorder, or a prior suicide attempt (see Table 4).¹⁷ A child who is uninterested in the future, has morbid preoccupations, and has suicidal ideation or fantasy should be evaluated for suicide risk with direct, nonjudgmental questioning.¹⁸ Immediate referral to a specialist and hospitalization are warranted for the child who has a plan to attempt suicide.¹⁶

 

TABLE 4 Profile of childhood suicide

The risk for a subsequent suicide attempt appears greatest 6 to 12 months after a previous attempt Girls are more likely to attempt suicide, and boys are more likely to succeed Young children who complete suicide tend to have above-average intelligence and exposure to other risk factors Risk factors include alcohol and drug use; a history of physical or sexual abuse; being pregnant, adopted, homosexual, bisexual, or unsure of sexual orientation; witnessing or being a victim of violence; having exposure to suicide; or having a gun in the home

Options for effective treatment

The primary care setting is appropriate for management of childhood depression, although complicated cases involving multiple comorbidities and those in which the child is at risk for self-harm or for harming others require referral to a child psychiatrist or psychiatric hospitalization.¹²

Psychotherapy, pharmacotherapy, and education are the mainstays of treatment for depression in children.^12,18 The child's stage of development should guide the choice of psychotherapy. Family, interpersonal, supportive, play, and group therapies may be useful in the treatment of mild or moderate depression, or as an adjunct to pharmacotherapy in severe depression.³ Cognitive-behavioral therapy (CBT) has been the most thoroughly tested and is effective in older children and adolescents. Using this form of therapy, children learn to recognize the activities that bring them pleasure, practice social skills, and implement effective problem solving.¹⁸

Fluoxetine (Prozac) is the only drug approved by the FDA for use in pediatric MDD.¹⁹ This selective serotonin reuptake inhibitor (SSRI) is generally well tolerated—the most common complaints reported involve mild GI disturbance, sedation, and headache. Changes in appetite and sleep patterns and conduct such as silly, daring, or agitated behavior have also been reported. Adverse effects seem to be dose dependent and subside with time.^3,12 The drug is metabolized by the CYP2D6 isoenzyme and should be used cautiously with other drugs that utilize this isoenzyme. In addition, concomitant use of other serotoninergic drugs may cause a serotonin syndrome. A recent study found that CBT together with fluoxetine therapy appears to have a protective effect on suicidal ideation and other self-harm events in adolescents.²⁰

The use of SSRIs in pediatric depression has recently received attention resulting from the reevaluation of multiple clinical trials performed in the early 1990s. In early 2004, the FDA asked the manufacturers of fluoxetine, sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), bupropion (Wellbutrin, Zyban), venlafaxine (Effexor), nefazodone (Serzone), and mirtazapine (Remeron) to include a statement in the drug labeling that recommends close observation for worsening depression or suicidal ideation in patients undergoing therapy with these agents. Although the FDA has not concluded that SSRIs worsen depression or increase suicidality, clinicians should monitor patients closely, particularly when initiating or terminating therapy.^19,21

The makers of venlafaxine and paroxetine have released letters to health care providers warning against the use of these drugs in patients younger than 18 years.^22,23 The letter regarding paroxetine was released only in the United Kingdom, where four SSRIs have been banned from use in children. The Medicine and Healthcare Products Regency Agency (the British equivalent of the US's FDA) advised clinicians against prescribing any SSRI except fluoxetine to children younger than 18 years, noting that evidence is lacking that the benefits of SSRIs outweigh the possible side effects in this group.²² Some of these drugs have not been sufficiently studied with clinical trials, and others have been associated with increased incidence of suicidal feelings, anxiety, insomnia, weight loss, and headaches in children.^24,25 The FDA continues to review available clinical trial data and expects to update its recommendation sometime this year.¹⁹

The choice of drug should take into account any comorbid conditions. Fluoxetine and sertraline, for example, are also indicated for anxiety and obsessive-compulsive disorders, providing dual therapy with a single drug in appropriate situations.^12,21,26

Although the reason is unknown, tricyclic antidepressants are not effective in children. In addition, their unfavorable side effect profile and potential for lethal overdose makes these drugs inappropriate for pediatric use.²⁷

Antidepressant effects usually take about 3 to 6 weeks to manifest themselves, although other effects may appear sooner.²⁶ Improvement should be followed by maintenance therapy for 4 to 6 months to prevent a recurrent episode. If symptoms do not improve after 6 weeks, treatment resistance and the possibilities of misdiagnosis and noncompliance should be considered. Another antidepressant may be tried if treatment resistance appears likely, although it is rare in children. At this stage of treatment, however, and with little data available regarding treatment for these patients, a pediatric psychiatric referral is warranted.²⁷ Despite treatment, as many as 40% of patients will have a recurrence of MDD within 2 years and 70% will have a recurrence within 5 years. Recommendations for terminating treatment call for a gradual decrease in dosage to minimize or avoid symptoms of withdrawal.¹⁹

Education is key in the management of childhood depression. Both the patient and the family should understand the difference between clinical depression and the typical growing pains of development: although most children experience periods of loneliness, rebellion, and confusion, depressed children feel this way all or most of the time.¹¹ Treatment adherence improves when the patient and family understand both the disorder and the effects of pharmacotherapy. A family or patient who resists the diagnosis of depression out of fear of social stigma must be educated about the disorder. Education may also diminish the feelings of blame and guilt often felt by the child or parents; clinicians can educate by explaining that depression does not simply result from the influence of a particular environment and is not preventable.¹² Resources available for practitioners, children, and their families are listed in "Depression resources on the Web."

In summary

Although depression is not uncommon among American children, clinicians often miss it. Because depression is associated with somatic complaints, social impairment, and suicide, health care providers must know the risk factors for depression and be able to recognize the symptoms and implement an effective treatment plan.

 

KEY POINTS in this article Although the prevalence of childhood depression in the United States is rising, it is often misdiagnosed or goes undetected, leaving affected children at a higher risk for social impairment, somatic complaints, academic difficulties, promiscuity, and substance abuse. The child's developmental stage may have a role in the presentation of depression. Appropriate and timely intervention is critical to forestall the devastating effects of the illness. Although few studies have looked at the management of childhood depression, experts agree that SSRIs should be considered first-line pharmacotherapy.

 

Depression resources on the Web • American Academy of Child and Adolescent Psychiatry: www.aacap.org • American Academy of Family Physicians: www.familydoctor.org • American Psychiatric Association: www.psych.org • American Psychological Association: www.apa.org • Depression and Bipolar Support Alliance: www.dbsalliance.org • National Alliance for the Mentally Ill: www.nami.org

REFERENCES

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19. FDA Public Health Advisory. Subject: Worsening depression and suicidality in patients being treated with antidepressant medications. US Food and Drug Administration Web site. Available at: http://www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.html. Accessed July 6, 2004.

20. March J, Silva S, Petrycki S, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA. 2004;292:807-820.

21. FDA Talk Paper. FDA issues public health advisory on cautions for use of antidepressants in adults and children. US Food and Drug Administration Web site. Available at: http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01283.html. Accessed July 6, 2004.

22. Alliance for Human Research Protection. Available at: http://www.researchprotection.org/risks/PaxilRisks0603.html. Accessed July 6, 2004.

23. Weller EB, Young KM, Rohrbaugh AH, Weller RA. Overview and assessment of the suicidal child. Depress Anxiety. 2001; 14(3):157-163.

24. Earth Crash Earth Spirit. British government bans four more "selective serotonin reuptake inhibitor" (SSRI) antidepressant drugs for use in children after studies show they can cause young patients to commit suicide. Available at: http://eces. org/articles/000560.php. Accessed July 6, 2004.

25. Medicines and Healthcare Products Regulatory Agency. Selective serotonin reuptake inhibitors (SSRIs): overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. Available at: http://medicines. mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages/ ssrioverview_101203.html. Accessed July 6, 2004.

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27. Weller E0B, Weller RA. Treatment options in the management of adolescent depression. J Affect Disord. December 2000; 61(suppl 1): 23-28.

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