Management of childhood depression

Approximately five percent of children and adolescents in the United States suffer from depression, which is often undiagnosed or untreated.¹ Untreated depression can have a serious impact on growth and development, yet the symptoms of almost two-thirds of children with depression go unrecognized by their primary-care provider (PCP), and only half of those whose depression is diagnosed receive adequate treatment.² Childhood depression
causes young patients to withdraw from activities. This may result in academic delays related to poor school performance, lost friendships, impaired social skills, interpersonal conflicts, and family dysfunction. The most serious complication of depression is attempted or completed suicide. 

The incidence of successful suicide in older children and adolescents is alarming. In 2005 alone, 4,482 young people between 10 and 24 years of age committed suicide, making it the third leading cause of death in this age group.³ In fact, suicide resulted in more deaths than the next four causes combined.³ Because of their frequent contact with children and adolescents, PCPs are in an ideal position to recognize the warning signs of depression and provide initial management.

Assessment and diagnosis

There are three types of childhood depression: major depressive disorder, dysthymia or dysthymic disorder, and bipolar affective disorder. Because the symptoms tend to be different than those seen in adults, diagnosis can be difficult. The hallmark of major depressive disorder (MDD) is a sad or depressed mood for at least two weeks. In children, the mood is most often described as irritability that manifests in various behavior problems. Younger children are likely to have somatic complaints (e.g., headache, upset stomach), leading the PCP to treat these symptoms without realizing they are signs of depression. Adolescents may engage in risky behavior (e.g., alcohol and drug use, dangerous driving, promiscuous sex) or antisocial behavior (e.g., stealing, vandalism, running away from home). They may become socially withdrawn or aggressive, or they may hurt others. Diagnosis is based on criteria established in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).⁴

Dysthymia or dysthymic disorder is a chronic depression that does not meet full MDD criteria and is present on most days for at least one year. Symptoms tend to be less life-threatening than those seen in MDD, but they are significant enough to interfere with the patient's general functioning and do warrant treatment.

Depression is one manifestation of bipolar affective disorder (BAD), previously called manic depressive disorder. Depressive incidents in BAD resemble those seen in MDD, but they eventually progress to episodes of mania that alternate with depression. When screening for depression, assess for any history of mania, since this is the primary difference between BAD and MDD.⁴ Unfortunately, if the patient presents with depression and has no history of manic episodes, BAD may be difficult to detect. Nevertheless, keep this differential diagnosis in mind, especially if treatment with antidepressant drugs results in agitation or other manic symptoms. BAD requires more complex pharmacologic management, and patients need referral to a psychiatric specialist. An additional concern with BAD is that the symptoms of mania resemble those of attention-deficit hyperactivity disorder (ADHD), and treatment with central nervous system stimulants or other drugs commonly used in ADHD can intensify mania. Children whose symptoms worsen on ADHD therapy need a psychiatric evaluation that includes screening for mood disorders.

Any child who is at high risk for depression or who presents with emotional problems as a primary complaint should be screened for depression.² Evaluating a child or adolescent for depression requires sufficient time for a thorough assessment and must include interviews of both the child and the family/caregivers. A complete history, physical examination, and battery of lab tests (Table 1) are needed to determine general health status and rule out medical problems with symptoms that can mimic depression (Table 2). Be aware of drugs that can cause depressionlike symptoms. These include antiseizure medications, sedatives, prednisone, beta blockers, oral contraceptives, nonsteroidal anti-inflammatory drugs, and stimulants. Screening for depression can begin with asking such open-ended questions as, “How are things going for you at home?” or “How is everything at school this year?” More direct questions are appropriate to elicit the presence or absence of specific depressive symptoms. However, specific instruments or questions that relate to DSM-IV criteria are necessary to correctly diagnose children (Table 3).

Assess for suicidal ideation in a direct manner. Ask the patient: “Are you thinking about hurting or killing yourself?” Depending on the response, other questions may be indicated, such as: “Do you have a plan?” and “How would you carry out this plan?” Expressed thoughts of suicide must always be taken seriously and require immediate referral to a mental-health specialist. 

Treatment

Treatment of depression includes ensuring safety, establishing a therapeutic relationship, and creating a social support system for the patient. Safety must be addressed first. If the child expresses thoughts of wanting to hurt him- or herself or others, immediate referral to a mental-health professional or the nearest emergency department is mandatory. The same rule applies if a child is acutely psychotic, aggressive toward others, or at risk of being abused or neglected at home. Prompt reporting and referral take precedence over confidentiality in any situation in which there is clear potential for harm to the patient and/or others.

The PCP has the advantage of an established relationship with the child and therefore plays a major role in the therapeutic plan. Family members are a vital component of the child's social support system and need to understand the importance of close supervision. Name a specific person the child should notify if he or she is feeling worse or having thoughts of self-harm. Provide family members with a telephone number they can call at any time if they are worried about changes in the child's mood or behavior. In addition to the immediate and extended family, the social support network can include the school nurse, a school counselor, sports coach, scout leader, member of the clergy, or any caring adult with whom the child has a trusting relationship.

Treatment plans for depression must include professional psychotherapy or counseling plus careful consideration of antidepressant medication.^5,6 Research shows that the best treatment response comes from a combination of therapy and antidepressant medications. PCPs often are not trained in psychotherapy but should be able to advise the family about its benefits.

Cognitive-behavioral therapy is used to treat depression in patients of all ages, and there is a large body of research supporting its effectiveness. The cognitive component consists of identifying and changing negative thoughts that can cause or contribute to a depressed mood (e.g., “I am a bad person,” “nobody cares about me,” “my life is all a mess,” etc.). The behavioral component focuses on setting specific goals and following through with such goal-directed actions as doing homework for short periods on school days or participating in one outside activity per week. Interpersonal therapy is another venue that allows the child to talk about troubling life situations and to learn and practice social skills for building better relationships with others.

Unfortunately, accessing professional psychotherapy can be quite difficult. Pediatric therapists are few in number and almost exclusively found in large urban areas. Psychotherapy can be expensive and may not be covered by the family's insurance plan. Support groups, if available, can be very helpful to patients and family members. The Web site of the National Alliance on Mental Illness is a good source of information about support groups. The child's school counselor may also know about groups available locally.

Medications

Antidepressant medication must be seriously considered. The use of psychotropic drugs in children has always been controversial because the long-term effects on developing brains are unknown. Antidepressant therapy became even more controversial in 2004 when the FDA began requiring drug manufacturers to place warning labels on all antidepressants. The FDA ruling was based on research studies indicating a small but statistically significant increased risk of suicidal thoughts and/or attempts in children and adolescents taking antidepressants.⁷ However, these studies did not show increased suicide completion, nor did they establish the base rate of suicide that would have occurred without treatment. Studies conducted since the ruling indicate that antidepressants are efficacious in the treatment of pediatric depression and that risks of increased suicidality do not outweigh the direct patient benefits of these medications.^2,8,9

Suicide in patients treated with antidepressants has been an issue ever since these drugs were first used in adults, and there are a number of potential explanations. Mood improvement typically does not take place for one month or more, while side effects tend to appear immediately. This can worsen the sense of hopelessness in the patient and contribute to the perception that the treatment is worse than the illness. Another possibility is that prior to starting treatment, the patient made —but was unable to implement—a suicide plan. The medication increases the energy level but the feeling of hopelessness does not lift, and the patient finds the strength to carry out the suicide plan. This is commonly referred to as “emergence.” Finally, there is the possibility that the patient who presents with major depression is actually showing the first signs of bipolar illness and will swing toward mania when treated with an antidepressant. Increased energy, irritability, agitation, and impulsiveness create a suicide risk in these patients and must be monitored accordingly.

PCPs must weigh the potential risks and benefits of any prescribed therapy. The risk of suicide is clearly present in a severely depressed person who is not adequately treated. Data compiled by the CDC show an increase in the suicide rates for children aged 10 to 19 years in the year following the FDA ruling on black-box warnings for antidepressants.³ A meta-analysis of studies measuring therapeutic effects and the incidence of suicidal thoughts and/or attempts in pediatric patients treated with antidepressants concluded that the potential benefits outweighed the risks.⁸

Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs for treatment of depression in children and adolescents (Table 4). Based on studies of safety and efficacy, fluoxetine (Prozac) is the only antidepressant with an official FDA indication for use in pediatric patients.¹⁰ Such other medications as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox) are prescribed off-label. The FDA advises that paroxetine (Paxil) should not be used in the pediatric population. SSRI starting doses should be the lowest possible, with cautious upward titration as indicated. Follow up by telephone within 72 hours, and schedule office visits at least once a week until the child's mood stabilizes. Make certain that neither the child nor the family thinks of the medication as a magic pill that will make things better immediately. Side effects tend to be worse in the first week, and the family needs to observe the child closely for untoward changes in mood or behavior.

Clear safety plans are essential for the families of children with depression. Families must be educated about the need to remove weapons and other means of carrying out lethal intentions (e.g., prescription medications, OTC medications, poisons, alcohol, ropes) from the home. Families must also be taught about the signs and risks of suicide. In the case of an adolescent or an older child, families may make an oral or verbal contract that spells out who the patient will notify if his or her suicidality or depression increases.² Recognize that treatment of a child or adolescent with depression includes active participation of the whole family in any management plan.

Although rare, serotonin syndrome is life-threatening, and children need emergency care if symptoms (e.g., fever, elevated pulse and BP, agitation, or delirium) develop. The risk of serotonin syndrome is greater with drug overdose, concurrent use of more than one SSRI, or taking an SSRI along with another antidepressant or St. John's wort. The combination of an SSRI with a monoamine oxidase inhibitor (MAOI) is especially dangerous.

Another group of drugs prescribed for adults are the so-called atypical antidepressants, a term used for newer drugs with varying pharmacologic actions. For some, the mechanism of action is unknown. Examples include bupropion (Wellbutrin), venlafaxine (Effexor), mirtazapine (Remeron), and duloxetine (Cymbalta). Although widely advertised and commonly prescribed for adults, there are not enough data to consider these medications to be first-line agents in children and adolescents, and the PCP should not prescribe them without consulting a specialist.

Two drug classes that should never be used in primary care are the tricyclic antidepressants (TCAs) and the MAOIs. Both classes have major safety problems, and neither has established effectiveness in the treatment of childhood depression.¹¹ TCAs have many side effects and drug interactions, and overdose is potentially fatal. MAOIs are notorious for multiple drug and food interactions, and failure to follow dietary modifications can result in serious complications (e.g., stroke). Overdose and interaction with other antidepressants carry a high risk of lethality. 

Putting it all together

Childhood depression is probably overlooked more than it is diagnosed and treated, and PCPs are often the first to identify the warning signs. Untreated childhood depression can adversely affect growth and development, increase the risk for substance abuse and other dangerous behaviors, and result in death by suicide. All PCPs should be able to recognize signs of depression and institute a basic plan that provides for safety, a therapeutic relationship, and ongoing social support for the patient. Referral to mental-health specialists is indicated for professional psychotherapy and must be considered if the PCP is uncertain about how to proceed once initial treatment fails or if the child's situation is potentially life-threatening. By virtue of an established relationship with children and their parents and the extensive background knowledge of the patient, PCPs can bring about positive outcomes for depressed children and adolescents.

Dr. Garzon is a pediatric nurse practitioner and assistant professor at the University of Missouri-St. Louis College of Nursing. Dr. Nelson is teaching assistant professor at the University of Missouri-St. Louis College of Nursing. Ms. Figgemeier is a pediatric nurse and graduate nurse practitioner student at the University of Missouri-St. Louis College of Nursing.

References

 
1. American Academy of Child and Adolescent Psychiatry. Depression in Children and Adolescents. Washington, D.C.: American Academy of Child and Adolescent Psychiatry: 2004.
2. Zuckerbrot RA, Cheung AH, Jensen PS, et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): I. Identification, assessment, and initial management. Pediatrics. 2007;120:e1299-e1312.
3.Centers for Disease Control and Prevention. Web-based injury statistics query and reporting syystem (WISQARS).
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, D.C.; American Psychiatric Association: 2000;356
5. 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.
6. Emslie G, Kratochvil C, Vitiello B, et al. Treatment for Adolescents with Depression Study (TADS): safety results. J Am Acad Child Adolesc Psychiatry. 2006;45:1440-1455.
7. U.S. Food and Drug Administration. Suicidality in children and adolescents being treated with antidepressant medications.
8. Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297:1683-1696.
9. Cheung AH, Zuckerbrot RA, Jensen PS, et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007;120:e1313-e1326.
10. Singh MK, Pfeifer JC, Barzman DH. Medical management of pediatric mood disorders. Pediatr Ann. 2007;36:552-563.
11. Hazell P, O'Connell D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents. Cochrane Database Syst Rev. 2002;(2):CD002317.

All electronic documents accessed September 16, 2009.