Assessment and Diagnosis of Pediatric Depression
        Assessment
        Diagnosis
Management of Pediatric Depression
        Pharmacologic management

There is limited information concerning the incidence of depression in healthy children. One study of children seen in a general practice showed that 38% had problems that required major intervention by a psychiatrist. Another study of children aged 7 to 12 years showed a 1.9% incidence of depression. If applied to the general population of the United States, these results show that 40,000 12-year-olds are depressed. Teachers have estimated that as many as 10% to 15% of their students are depressed. The Joint Commission on Mental Health of Children states that 1.4 million children younger than 18 years need immediate help for disorders such as depression; only one third of these children receive help for their disorder.[1]

Most children cope with the emotional upheaval related to cancer and demonstrate not only evidence of adaptation but positive psychosocial growth and development. A minority of children, however, develops psychological problems including depression, anxiety, sleep disturbances, difficulties in interpersonal relationships, and noncompliance with treatment. These children require referral and intervention by a mental health specialist.[2]

In one of the first studies of depression in childhood cancer, 114 children and adolescents were studied, and 59% were found to have mild psychiatric problems.[3] A study of 17 adolescent and 21 pediatric oncology patients, all of whom were administered a self-report psychosocial life events inventory, showed that the adolescent samples had a mean level of depressive symptoms similar to that of the general population. The pediatric oncology sample demonstrated significantly lower depressive symptoms than the general population.[4] Forty-one adolescent survivors of childhood cancer were assessed using questionnaires and interviews to determine the psychosocial status of the survivors; most survivors were functioning well, and depression was rare.[5] A study of long-term cancer survivors and their mothers, comparing the survivors with a group of 92 healthy children, showed that the majority of former patients were functioning within normal limits. Not surprisingly, children with severe late effects had more depressive symptoms.[6] One researcher looked at the characteristics of psychiatric consultations in a pediatric cancer center and found that adjustment disorder was the chief psychosocial diagnosis. This finding is similar to results obtained from adult cancer patients. This study also found that anxiety reactions were more common in the younger pediatric patients and depressive disorders were more common in older patients.[7] In a study conducted in 1988 with a sample of 30 adolescent cancer patients, the rate of major depression was not greater than the rate for the population at large.[8] One review reported a 17% incidence of depression using the Diagnostic and Statistical Manual for Mental Disorders, 3rd Edition criteria.[9]

Most cancer survivors demonstrate general resiliency and successful psychological adjustment to the disease and its treatment. Despite evidence for successful adaptation, most studies document psychological difficulties in a significant subset of cancer survivors.

The term depression refers to a symptom, a syndrome, a set of psychological responses, or to an illness.[1] Duration and intensity of the behavioral manifestation (e.g., sadness) differentiates the symptoms from the disorder. For example, a sad affect can be a child's response to trauma and is usually of short duration; however, a depressive illness is characterized by long duration, and is associated with insomnia, irritability, changes in eating habits, and severe impairment of the child's scholastic and social adjustment. Depression should be considered whenever any behavior problem persists. Depression does not refer to transitory moments of sadness, but rather to a disorder that affects development and interferes with realization of the child's innate potential.[1]

Some manifestations of depression in a school-aged child include anorexia, lethargy, sad affect, aggression, weeping, hyperactivity, somatization, fear of death, frustration, feelings of sadness or hopelessness, self criticism, frequent day dreaming, low self-esteem, school refusal, learning problems, slow movements, vacillating hostility towards parents and teachers, and loss of interest in previously pleasurable activities. Differentiating these symptoms from behavioral responses to normal developmental stages is important.[1]

Assessment of depression includes determination of the child's family situation, level of emotional maturity, ability to cope with illness and treatment, age, state of development, previous experience with illness, and personal ego strength.[10]

A comprehensive assessment for childhood depression is the basis for accurate diagnosis and treatment. Evaluation of the child and family situation focuses on the pediatric health history, behaviors observed by the practitioner or reported by others (e.g., parents, teachers), interviews with the child, and judicial use of tests such as the Beck Depression Inventory or the Child Behavior Checklist.[10]

In discussing the diagnosis of childhood depression, experts stress the importance of understanding childhood depression as an entity distinct from depression in adults. This is due to the fact that developmental issues in childhood are distinctly different from those of adulthood.[11]

A model of childhood affective disorders uses the following explicit criteria:[12]

• Dysphoric mood (children younger than 6 years must also have a sad facial expression).
• At least 4 of the following signs or symptoms present every day for a period of at least 2 weeks:
  • Appetite disturbance.
  • Insomnia or hypersomnia.
  • Psychomotor agitation or retardation.
  • Loss of interest or pleasure in usual activities (children younger than 6 years must also have signs of apathy).
  • Fatigue or loss of energy.
  • Feelings of worthlessness, self-reproach, or excessive, inappropriate guilt.
  • Diminished ability to think or concentrate.
  • Recurrent thoughts of death or suicide.

Treatment regimens implemented in childhood depression reflect theoretical models, etiology, and manifestations of the disorder.[1] Individual and group psychotherapy are commonly utilized as the primary treatment modality and are directed at helping the child to master his or her difficulties and to enable the child to develop in an optimal manner. Play therapy may be used as a means of exploring a younger child's view of himself or herself, the disease, and its treatment. The child needs to be helped from the beginning to explore and understand, at a level appropriate for his or her developmental age, the diagnosis of cancer and the treatments involved.[1]

As is the case with depression in adult cancer patients, there are few, if any, revealing trials of antidepressants in children with cancer. One author described rapid clinical response to low doses (<2 mg/kg/day) of imipramine or amitriptyline for 8 depressed children with cancer.[13] Another author described the use of benzodiazepines such as lorazepam, diazepam, alprazolam, and clonazepam for the treatment of anxiety disorders. Trials of benzodiazepines should be short term. These drugs should be tapered slowly when they are discontinued.[14]

The combined use of tricyclic antidepressants and neuroleptics in the management of 3 children with severe symptoms of depression and anxiety has been reported. The children studied were in the terminal phases of their disease and were treated with a combination of low-dose amitriptyline and haloperidol. Levels of anxiety and depression were decreased, and this intervention allowed the patients and their families to deal with issues involved in death and dying.[15]

Significant concern about the potential for suicide as a side effect of selective serotonin reuptake inhibitors (SSRIs) has led the U.S. Food and Drug Administration (FDA) to issue a caution about their use that includes the importance of careful monitoring of potential risks.[16] Before this FDA Health Advisory was issued, clinical experience and the results of small clinical trials suggested that antidepressants can be safely administered to adult cancer patients, although there are no controlled clinical trials to support this position. The risk/benefit ratio for use of SSRIs may not be as favorable for children and adolescents. Several multicenter, double-blind, randomized, placebo-controlled clinical trials using SSRIs with children and adolescents with major depressive disorder but not cancer found modest improvements for fluoxetine,[17,18] paroxetine,[19] and sertraline.[20] Balancing these improvements were reports of serious adverse events that included worsening of psychiatric symptoms, increased suicidal ideation and gestures, increased conduct problems or hostility with paroxetine,[19] and suicide and suicide attempts with sertraline.[20] None of these clinical trials have included or focused on children and adolescents being treated for cancer. Risk/benefit concerns have reached the level of international regulatory concern. The Medicines and Healthcare Products Regulatory Agency of Great Britain has recommended that most of the drugs in the SSRI category not be used with children and adolescents,[21] and the FDA raised similar concerns in a Talk Paper and subsequently issued a “black box” warning.[16] A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies [22] (including seven studies not included in the initial meta-analysis [23]) using a random-effects model. While this reanalysis found an overall increased risk of suicidal ideation/suicide attempt consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant.[22] Furthermore, another study examining the U.S. and Dutch data suggests a drop in SSRI prescriptions for children and adolescents and a simultaneous increase in suicide rates in this patient population since the FDA Health Advisory was issued.[24] In summary, the risk-benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality.[25] The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients.[26] Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years with major depression, only fluoxetine showed benefit over placebo.[22] As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or central nervous system radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation from a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial.

Refer to the PDQ summary on Pediatric Supportive Care for more information.

References

1. Deuber CM: Depression in the school-aged child: implications for primary care. Nurse Pract 7 (8): 26-30, 68, 1982.  [PUBMED Abstract]
   
   
2. Kazak AE: Psychological issues in childhood cancer survivors. J Assoc Pediatr Oncol Nurses 6 (1): 15-6, 1989.  [PUBMED Abstract]
   
   
3. O'Malley JE, Koocher G, Foster D, et al.: Psychiatric sequelae of surviving childhood cancer. Am J Orthopsychiatry 49 (4): 608-16, 1979.  [PUBMED Abstract]
   
   
4. Kaplan SL, Busner J, Weinhold C, et al.: Depressive symptoms in children and adolescents with cancer: a longitudinal study. J Am Acad Child Adolesc Psychiatry 26 (5): 782-7, 1987.  [PUBMED Abstract]
   
   
5. Fritz GK, Williams JR, Amylon M: After treatment ends: psychosocial sequelae in pediatric cancer survivors. Am J Orthopsychiatry 58 (4): 552-61, 1988.  [PUBMED Abstract]
   
   
6. Greenberg HS, Kazak AE, Meadows AT: Psychologic functioning in 8- to 16-year-old cancer survivors and their parents. J Pediatr 114 (3): 488-93, 1989.  [PUBMED Abstract]
   
   
7. Rait DS, Jacobsen PB, Lederberg MS, et al.: Characteristics of psychiatric consultations in a pediatric cancer center. Am J Psychiatry 145 (3): 363-4, 1988.  [PUBMED Abstract]
   
   
8. Tebbi CK, Bromberg C, Mallon JC: Self-reported depression in adolescent cancer patients. Am J Pediatr Hematol Oncol 10 (3): 185-90, 1988 Fall.  [PUBMED Abstract]
   
   
9. Kashani J, Hakami N: Depression in children and adolescents with malignancy. Can J Psychiatry 27 (6): 474-7, 1982.  [PUBMED Abstract]
   
   
10. Archenbach TM, ed.: Manual for the Child Behavior Checklist and Revised Child Behavior Profile. Burlington, Vt: T.M. Achenbach, 1983. 
    
    
11. American Psychiatric Association.: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. 4th rev. ed. Washington, DC: American Psychiatric Association, 2000. 
    
    
12. Malmquist CP: Major depression in childhood: why don't we know more? Am J Orthopsychiatry 53 (2): 262-8, 1983. 
    
    
13. Pfefferbaum-Levine B, Kumor K, Cangir A, et al.: Tricyclic antidepressants for children with cancer. Am J Psychiatry 140 (8): 1074-6, 1983.  [PUBMED Abstract]
    
    
14. Coffey BJ: Review and update: benzodiazepines in childhood and adolescence. Psychiatr Ann 23 (6): 332-9, 1993. 
    
    
15. Maisami M, Sohmer BH, Coyle JT: Combined use of tricyclic antidepressants and neuroleptics in the management of terminally ill children: a report on three cases. J Am Acad Child Psychiatry 24 (4): 487-9, 1985.  [PUBMED Abstract]
    
    
16. U.S. Food and Drug Administration.: Antidepressant Use in Children, Adolescents, and Adults. Rockville, Md: Food and Drug Administration, Center for Drug Evaluation and Research, 2007. Available online. Last accessed December 15, 2008. 
    
    
17. Emslie GJ, Rush AJ, Weinberg WA, et al.: A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 54 (11): 1031-7, 1997.  [PUBMED Abstract]
    
    
18. Emslie GJ, Heiligenstein JH, Wagner KD, et al.: Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 41 (10): 1205-15, 2002.  [PUBMED Abstract]
    
    
19. Keller MB, Ryan ND, Strober M, et al.: Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 40 (7): 762-72, 2001.  [PUBMED Abstract]
    
    
20. Wagner KD, Ambrosini P, Rynn M, et al.: Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 290 (8): 1033-41, 2003.  [PUBMED Abstract]
    
    
21. Safety Review of Antidepressants Used by Children Completed. London, UK: Medicines and Healthcare Products Regulatory Agency, 2003. Available online. Last accessed December 15, 2008. 
    
    
22. 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 297 (15): 1683-96, 2007.  [PUBMED Abstract]
    
    
23. Hammad TA, Laughren T, Racoosin J: Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 63 (3): 332-9, 2006.  [PUBMED Abstract]
    
    
24. 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): 1356-63, 2007.  [PUBMED Abstract]
    
    
25. Leon AC: The revised black box warning for antidepressants sets a public health experiment in motion. J Clin Psychiatry 68 (7): 1139-41, 2007.  [PUBMED Abstract]
    
    
26. Ramchandani P: Treatment of major depressive disorder in children and adolescents. BMJ 328 (7430): 3-4, 2004.  [PUBMED Abstract]
    
    

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