Pediatric Annals

Pediatric Management of Depression

Elizabeth B Weller, MD; Ronald A Weller, MD

Abstract

Children and adolescents have depressive episodes with symptoms similar to those observed in depressed adults. As awareness of depression in this age group has increased, research activity has correspondingly increased. Descriptive and, more recently, biological studies have been undertaken; however, many are preliminary and await replication. New treatment strategies for depressive disorders are currently being developed and studied.

DEFINITION

According to the American Psychiatric Association's Diagnostic and Statistical Manual, ed 3, Revised (DSM-III-R),1 mood disorders occur in infants, children, and adolescents. Diagnosis is made by the same criteria used for adults with minor modifications that account for the different developmental levels observed in children. Although bipolar disorders were once believed to be nonexistent in prepubertal children, evidence indicates children experience both unipolar and bipolar affective disorders.2,3 Symptoms of these disorders should be carefully evaluated and fully considered in the differential diagnosis of children and adolescents. This should occur both routinely and in complicated cases with unusual presentations or psychotic features.

MAJOR DEPRESSIVE EPISODE

The DSM-III-R is the diagnostic system used to define psychiatric illness in the United States. It is a modification of DSM-III, which was introduced in 1980. The DSM-III and DSM-III-R criteria for major depression are quite similar. A diagnosis of major depressive disorder requires five or more of the following symptoms: (1) depressed mood; (2) loss of interest or pleasure; (3) significant weight loss or gain (eg >5% of body weight in a month or failure of children to make expected weight gains); (4) insomnia or hypersomnia; (5) psychomotor agitation or retardation; (6) fatigue or loss of energy; (7) feelings of worthlessness or excessive or inappropriate guilt; (8) diminished concentration; (9) recurrent thoughts of death, suicidal ideation, a specific plan for committing suicide, or a suicide attempt. These symptoms should be present concurrently for at least two weeks. Depression is not diagnosed if an organic factor initiated or maintained the depression or if the depression was a reaction to the death of a loved one. Hallucinations and delusions may be present, but they should not be observed for more than two weeks in the absence of depressive symptoms. Finally, depression should not be diagnosed in children with a previous diagnosis of schizophrenia or schizophreniform, delusional, or other psychotic disorders.

EPIDEMIOLOGY

Reported prevalence rates of depression in children have varied widely. This variation results in part from differences in samples studied, sample sizes and associated characteristics, the diagnostic criteria employed, and the age of the subjects. A study of preschoolers by Kashani et al4 drawn from the general population reported a prevalence of 0.3%. This study concluded depression diagnosed using adult criteria was not frequent in preschoolers. Studies in the United States and New Zealand found a population prevalence of 1.8% in prepubertal children.4 This rate rose dramatically to 4.7% in 14- to 16-year-old adolescents. Increased prevalence during adolescence was attributed to biological changes associated with puberty rather than an increase in chronological age. Also, the incidence of depression in females increased with puberty.

In clinically derived samples, depression has been found in 28% of children attending a psychiatric outpatient clinic, 53% of those evaluated in an educational diagnostic center, 7% of general pediatric medical inpatients, and 40% of pediatric neurologic inpatients. The rate of depression among psychiatrically hospitalized children ranged from 13% in a community mental health center to 59% in a general psychiatric hospital.5

The recent use of standardized diagnostic techniques including structured and semi-structured interviews, self-report and clinician rating scales, and reports from parents and teachers has made it easier to diagnose depression. In general, studies using these techniques have found that childhood depression is…

Children and adolescents have depressive episodes with symptoms similar to those observed in depressed adults. As awareness of depression in this age group has increased, research activity has correspondingly increased. Descriptive and, more recently, biological studies have been undertaken; however, many are preliminary and await replication. New treatment strategies for depressive disorders are currently being developed and studied.

DEFINITION

According to the American Psychiatric Association's Diagnostic and Statistical Manual, ed 3, Revised (DSM-III-R),1 mood disorders occur in infants, children, and adolescents. Diagnosis is made by the same criteria used for adults with minor modifications that account for the different developmental levels observed in children. Although bipolar disorders were once believed to be nonexistent in prepubertal children, evidence indicates children experience both unipolar and bipolar affective disorders.2,3 Symptoms of these disorders should be carefully evaluated and fully considered in the differential diagnosis of children and adolescents. This should occur both routinely and in complicated cases with unusual presentations or psychotic features.

MAJOR DEPRESSIVE EPISODE

The DSM-III-R is the diagnostic system used to define psychiatric illness in the United States. It is a modification of DSM-III, which was introduced in 1980. The DSM-III and DSM-III-R criteria for major depression are quite similar. A diagnosis of major depressive disorder requires five or more of the following symptoms: (1) depressed mood; (2) loss of interest or pleasure; (3) significant weight loss or gain (eg >5% of body weight in a month or failure of children to make expected weight gains); (4) insomnia or hypersomnia; (5) psychomotor agitation or retardation; (6) fatigue or loss of energy; (7) feelings of worthlessness or excessive or inappropriate guilt; (8) diminished concentration; (9) recurrent thoughts of death, suicidal ideation, a specific plan for committing suicide, or a suicide attempt. These symptoms should be present concurrently for at least two weeks. Depression is not diagnosed if an organic factor initiated or maintained the depression or if the depression was a reaction to the death of a loved one. Hallucinations and delusions may be present, but they should not be observed for more than two weeks in the absence of depressive symptoms. Finally, depression should not be diagnosed in children with a previous diagnosis of schizophrenia or schizophreniform, delusional, or other psychotic disorders.

EPIDEMIOLOGY

Reported prevalence rates of depression in children have varied widely. This variation results in part from differences in samples studied, sample sizes and associated characteristics, the diagnostic criteria employed, and the age of the subjects. A study of preschoolers by Kashani et al4 drawn from the general population reported a prevalence of 0.3%. This study concluded depression diagnosed using adult criteria was not frequent in preschoolers. Studies in the United States and New Zealand found a population prevalence of 1.8% in prepubertal children.4 This rate rose dramatically to 4.7% in 14- to 16-year-old adolescents. Increased prevalence during adolescence was attributed to biological changes associated with puberty rather than an increase in chronological age. Also, the incidence of depression in females increased with puberty.

In clinically derived samples, depression has been found in 28% of children attending a psychiatric outpatient clinic, 53% of those evaluated in an educational diagnostic center, 7% of general pediatric medical inpatients, and 40% of pediatric neurologic inpatients. The rate of depression among psychiatrically hospitalized children ranged from 13% in a community mental health center to 59% in a general psychiatric hospital.5

The recent use of standardized diagnostic techniques including structured and semi-structured interviews, self-report and clinician rating scales, and reports from parents and teachers has made it easier to diagnose depression. In general, studies using these techniques have found that childhood depression is not as rare as previously believed.

Prepubertal Children

With advancing age, children become more adept in using language to communicate problems. When this occurs, children must be interviewed individually; a combined interview with their parents is not sufficient. Children will be able to report internal experiences of sadness, suicidal thoughts, and sleep disturbances of which their parents may be unaware. On the other hand, parents will often provide better informa' tion on symptoms that the child would tend to minimize, such as poor social functioning, irritability, and lack of interest in usual activities. Of depressed children, only 25% will have enough symptoms reported independently by child and parent to diagnose depression. If information is taken only from the children, one fourth of depressions will be missed; if only parents are interviewed, half of depressions will be missed.6

After 6 years of age, diagnostic interviews (eg, the Diagnostic Interview for Children and Adolescents and the schedule for affective disorders and schizophrenia, child version), self-report rating scales (eg, the Children's Depression Inventory [CDI]), and clinician rating scales (eg, the CDRS-R) can be used to assess depression.5 Except for the CDI, these instruments are time consuming. They can be used for baseline evaluations during an index episode as well as for follow-up to provide systematic and objective information.

Adolescents

A clear onset for an affective episode is more likely in adolescents than in prepubertal children. Adolescent onset depression is more like adult depression than is prepubertal depression. In adolescents drug and alcohol abuse may complicate affective symptomatology; approximately 20% of adolescents with affective disorder present with drug abuse. 7 In some, this may be an attempt to self-medicate. Longitudinal history and chronology of symptoms are key to separating depression and substance abuse. A diagnosis of primary affective disorder indicates no other psychiatric disorders preceded the onset of the affective disorder. A secondary affective disorder indicates another psychiatric disorder (eg, attention deficit hyperactivity disorder [ADHD], conduct disorder, separation anxiety disorder, obsessive compulsive disorder, substance abuse, or a serious medical condition) predated the affective disorder. In cases of preexisting substance abuse, an affective disorder should not be diagnosed until the child is drug-free and is no longer at risk for developing symptoms of withdrawal from the drug.

Symptoms of conduct disorder, ie, fighting and arguing, may also be encountered in depressed children. In primary conduct disorder with secondary depression, successful treatment of depression may not affect the conduct disorder. However, if the child has primary depression with some features of conduct disturbance, ie, inordinate amount of aggression due to irritability or poor school attendance, then treatment of the depression usually alleviates these accompanying conduct problems, particularly if they were not present prior to the onset of the depression.

DIFFERENTIAL DIAGNOSIS

In children and adolescents, differential diagnosis should be carefully considered. Before making a psychiatric diagnosis in a child or adolescent, organic conditions such as brain tumors, multiple sclerosis, or degenerative brain disorders that mimic or cause psychiatric symptoms should be ruled out. Incidence of such conditions may vary according to age. Thus, knowledge of normal development and physical illnesses with psychiatric manifestations are necessary to make an accurate diagnosis. For example, preschoolers presenting with depressive syndromes should also be evaluated for malignancies and neglect or abuse.

In prepubertal children, the differential diagnosis for depression includes separation anxiety disorder, overanxious disorder, adjustment disorder with depressed mood, and conduct disorder. For adolescents substance abuse, anxiety disorders, and early schizophrenia must be carefully ruled out. When it is unclear whether the patient has an affective disorder or schizophrenia, any error should be toward diagnosing and treating an affective disorder. Depending on response, the treatment strategy can be altered.

Another diagnosis often considered in the differential diagnosis in adolescents is borderline personality disorder. Too frequently, this diagnosis is given to adolescents without a thorough evaluation. Borderline personality disorder almost vanished from an adolescent psychiatric ward when diagnostic interviews supplemented routine admission clinical interviews6; the majority of these youngsters fulfilled DSMIII-R criteria for an affective disorder when examined this way. This observation is compatible with the theory that borderline personality disorder may represent an atypical presentation of an affective disorder.6

TREATMENT

A biopsychosocial approach is commonly used to treat affective disorders in children. Educating the child and family about childhood depression is particularly important. Parents frequently feel they might have caused the condition because of inadequate parenting skills. Parents have often been blamed for causing problems in their children and subsequently have been alienated from the child's treatment. It is preferable to educate parents and elicit their help in providing care for the child as this leads to better results. In a severe episode of depression, intensive psychotherapy alone is rarely effective. However, a caring, supportive clinician who sets limits for the child or adolescent may be particularly effective. In more severe depressions, medication may be indicated. Unfortunately, children and teenagers are frequently reluctant to take medications as they do not want to be different from peers.

Doctor-patient confidentiality should be emphasized and followed except in situations where there is a possibility of suicide or homicide. Children and adolescents should be assured that the physicians role is to facilitate communication between them and their families. This, however, should be done in family sessions with the child present. The physician should not be a messenger between child and parent.

The average estimated length of an untreated major depressive episode is eight months.8 Early treatment should be initiated with the hope of avoiding school failure, which can exacerbate the already low selfesteem of depressed children. Initially, it must be decided whether inpatient or outpatient treatment is needed. Treatment should be in the least restrictive environment; however, some situations require hospitalization. If a youngster is suicidal and the family is not able to provide constant monitoring, the child should be hospitalized for protection. Children medicating themselves with drugs and alcohol may require hospitalization as outpatient treatment may not prevent their use of drugs or alcohol. Also, children with irritability as a major part of their depressive disorder may engage in self-destructive behavior such as fighting with peers or parents, and hospitalization may prevent harm to themselves or others. Diagnostic dilemmas, particularly first episodes of psychosis with affective symptoms, may be resolved more quickly and safely in the hospital. The hospital provides a structured environment and gives the physician frequent direct access to the patient. Additional behavioral observations by well trained psychiatric nursing staff, social workers, and teachers are easily obtained and invaluable.

PHARMACOTHERAPY

To date, most treatment studies have focused on pharmacotherapy. Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and lithium carbonate have all been used to treat depressed children and adolescents.5 Frommer9 reported MAOI drugs as the treatment of choice for children with uncomplicated depression, a depressive phobic anxiety state, and some with enuretic depression. Annell10 reported lithium was successful in treating children with affective symptoms. However, the most commonly used medications in treating childhood depression have been the TCAs.

Before treating a child with a TCA, a complete blood count (CBC) with differential, electrolytes, thyroid function tests (T3, T4, TSH), blood urea nitrogen (BUN), serum creatinine, liver function tests, and an EKG should be performed. A properly performed Dexamethasone Suppression Test (DST), where the standard exclusion and inclusion criteria are carefully followed, may prove useful in monitoring treatment.11,12 Preliminary research suggests children whose DST remains abnormal despite clinical improvement may be at a greater risk for relapse.11

Plasma TCA monitoring is useful in children and adolescents, helping to insure compliance and to monitor for cardiotoxicity and neurotoxicity. Children with plasma levels greater than 500 ng/mL are at a higher risk for developing increased PR interval, ST segment suppression, and increased diastolic blood pressure. A recent study by Preskom et al13 showed children with high plasma TCA levels can develop a toxic state that might be misinterpreted as unresponsiveness to drug treatment. This misinterpretation might result in incorrectly increasing the dose of TCA when a reduction is needed. Unfortunately, wide variations in plasma levels exist among children receiving the same fixed dose.14 Thus, actual dose is not a good measure of adequacy of treatment. For example, if total daily dose of Imipramine is 75 mg or less, 80% of depressed children will not respond.

If TCAs are to be used, parents should be informed that Imipramine and other TCAs have not been approved by the Food and Drug Administration for treating depressed children less than 12 years old. Parents should also be taught to take the child's resting pulse and to carefully observe their children to spot potential complications. This is particularly important in the summer when outdoor activities are frequent. Children can also learn to monitor themselves for side effects without provoking undue concern on their part.

Imipramine has been given in a single bedtime dose or in multiple doses throughout the day. The daily dose normally should not exceed 5 mg/kg. However, doses as high as 7 mg/kg have been used with close monitoring of EKG and vital signs by Puig-Antich. 7 The average dose in one treatment study of prepubertal children was 150 mg per day, although some required doses of 200 mg per day or more. However, as mentioned earlier, plasma level, not actual dose, is most important in predicting response. Caution should be used in increasing the dose in obese children as they may tend to accumulate the drug in fatty tissue, which could cause complications. A typical dosing regimen utilizes a starting dose of 1.5 mg/kg per day that is increased by 1.0 to 1.5 mg/kg every third day up to a maximum of 5 mg/kg total daily dose.

As mentioned above, side effects should be monitored. Both children and parents can be asked about their occurrence. Pulse, lying and sitting blood pressures, serial EKGs, and plasma drug levels should be obtained. Prolongation of PR interval on EKG should not exceed 0.21 seconds, QRS should not be prolonged by more than 30% over baseline, resting pulse should not exceed 130 beats per minute, and blood pressure should not exceed 140/90. If these parameters are exceeded, the dose should be lowered and the patient observed closely. Open studies found 75% of moderately to severely depressed children responded to TCA treatment.5 Reported response rates of TCAs in adolescents are somewhat less, ie, in the range of 40%. 7 Some have postulated the high levels of sex hormones that occur during adolescence may decrease the efficiency of TCAs.

Lithium carbonate is another medication that should be considered in the treatment of depressed children and adolescents. Although less studied than the TCAs in depressed children, lithium has been used to treat tricyclic resistant depression as well as bipolar illness and aggressive-impulsive behavior. A dosage guide for lithium carbonate for prepubertal children based on weight and body surface area can be used to select an appropriate target dose.15 Prior to initiation of lithium treatment, CBC with differential, electrolytes, liver function tests, BUN, creatinine, creatinine clearance, thyroid function tests, urine osmolality, and a pregnancy test in pubertal females should be done. Throughout treatment, lithium should be monitored carefully as its long-term effect on growing children is unknown. It is also deposited in bone, but whether this is of clinical significance is not known. Fortunately, children and adolescents seem to tolerate lithium better than adults. As yet there are no published reports defining the optimal therapeutic range for lithium in children. However, lithium levels higher than 1.4 mEq/L should probably be avoided. Side effects and clinical response should be considered in deciding dosage changes.

Once a good response has been obtained, treatment both with TCAs and lithium should be continued 4 to 6 months following clinical response. The dose should then be tapered and discontinued at appropriate times, ie, avoid discontinuing medications at stressful times such as exams. Some children manifest a flu-like syndrome with nausea, vomiting, abdominal pain, and feelings of tiredness after abrupt tricyclic withdrawal. This is often misinterpreted by parents as recurrence of depression. Treating affectively ill children with medication alone may not always yield maximum improvement. Concomitant group therapy, social skills training, and family and individual therapy may also be beneficial.

SUMMARY

Depression in children and adolescents is well recognized. The current approach to manage a depressed child or adolescent is to combine individual psychotherapy, parent education and family therapy, as well as pharmacotherapy after a thorough assessment to make the proper diagnosis of depression. This requires several hours of seeing the child, the parent, and other family members (affective disorders run in families) alone as well as parent and child together. Situational reasons for depressed affect and depressive symptomatology should not be treated with medications as these are most amenable to environmental manipulation as well as psychotherapies. Very often depressed children are misdiagnosed as having attention deficit hyperactivity (ADHD) or conduct disorder instead of depression, or conversely, major depression is diagnosed when other situational problems have overwhelmed the family.

Once the diagnosis of major depression is made it should be decided whether an outpatient or inpatient program is indicated. If a child is at risk for suicide, immediate hospitalization is necessary. If the decision is made to treat the major depressive episode with medication, the physician should be familiar with proper medication doses and should watch for side effects. Too often children are given inadequate doses of antidepressants by physicians. When very small amounts of TCAs are given, ie, 10 mg t. i.d. , the child often suffers from side effects but does not feel relief from depressive symptomatology.

As the prevalence of depression has only recently been fully recognized in prepubertal children, many practicing physicians have not been exposed to the diagnosis and treatment of depression in children during their training. The evaluation and treatment of a depressed child or adolescent should not be undertaken unless the physician is able to manage all aspects of the child's care. If the physician is unable to fully diagnose and manage depressed children and depression is suspected, consultation with a child and adolescent psychiatrist for second opinion is indicated.

Unfortunately, the Graduate Medical Educational Advisory Council (GMENAC) estimates that 4,900 additional child and adolescent psychiatrists will be needed by 1990. l6 If pediatricians and family practitioners are called upon to evaluate increasing numbers of depressed children, departments of pediatrics and family practice may need to provide additional training in psychiatry, such as rotating residents in inpatient, outpatient, and consultation services with properly trained child and adolescent psychiatrists. As many families consider the pediatrician or family practitioner as the first to help with psychiatric problems, such additional psychiatric training could significantly improve the treatment of depressed children.

With increasing recognition of depression in children and adolescents, physicians will be called on to evaluate and treat them, and physicians not prepared in this area must seek additional training. It is hoped that training programs in pediatrics and family medicine will increase training opportunities in the management of depression and other childhood psychiatric problems so that patients will have ready access to currently available treatments.

REFERENCES

1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 3. Revised. Washington. DC, American Psychiatric Association, 1987.

2. Canrwell DP, Carlson GA: Affective Disorders m Childhood and Adolescence: An Update. New York, Spectrum Publications, 1983.

3. Poznanski EO, Causaran JA . Buchsbaum Y. et al: Preliminary sciatic* of the reliability and validity of the Children's Depression Rating Scale. ) Am Acad ChHd Psychiatry 1984; 23:191-197.

4. Kashani JH. Sherman DD: Childhood depression: Epidemiology, etiological models. and treatment implication*. Integranw Psychiatry 1988; 6:1-21.

5. Weller EB. Weller RA: Currcnf fVrspecthes un Motor DepmssKt Disorders m Children. Washington. DC, American Psychiatrie Pre», 1984.

6. Akiskal HS, Weller EB: Mood disorders and suicide in children and adolescenti, in Kaplan HI. Sadock BJ (eds): Cumprdwnstre Textbook of Prychiatry/V. New York. New York University School of Medicine (in press).

7. Purg-Anrich J: Affective disorders in children and adolescents: Diagnostic validity and psychobiology. in Meltzer HY (ed): Psychupharmaculue? - the Third Generation of Progress. New York. Raven Press. 1987, ? 84 J.

8. Kuvacs M. Feinbert TL, Ctouse MA. et al: Recovery in childhood depressive disorders: A longitudinal prospective study. Arch Gen Psycntutr? 1984: 41:229.

9. Frommer E: Depressive illness in childhood. BrJ Psychiatry 1968; 2:117-136.

10. Annell AL: Lithium in the treatment of children and adolescents. Acta Psychiatr Scand (Suppl) 1969; 207:19-30.

11. Weller EB. Wellet RA. Fristad MA: Lithium dosage guide for prepubertal children: A preliminary report. J Am Acad ChM Psychiatry 1986; 25:92-95.

12. Weller EB. Weller RA: Neuroendocrine changes in affectively til children and adolescents, in Brown W (ed): Enduirmofoffi and Mewtwism CImics of North America. Philadelphia. WB Saunders Co. 1988.

13. Preskorn SH. Weller EB, Hughes CW. et al: Depression in prepubertal children: Dexamerhasone nonsuppression predicts differential response to Imipramine vs placebo. Psychopharmacol Bull 1987; 23.128.

14. Weller EB. Weller RA. Preskom SH. et al: Steady-state plasma Imipramine levels in prepubertal depressed children. Am J Psychiatry 1982: 19:506-508.

15. Weller RA. Weiler EB. Fristad MA. et ab Dexamethasone Suppression Test and clinical outcome in prepubertal depressed children. Am J Psvcfuairv 1986; 143:1469-1470.

16. Report of the Graduate Medical Education National Advisory Committee tu the Secretary: Vol I. Summary Department of Health and Human Services. Health Resources Administration Office of Graduate Medication Education. 1980.

10.3928/0090-4481-19890201-07

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