Depression in children

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Pediatric health: depression in children

Depression is a serious but often overlooked disorder in children. Depressed children suffer a reduced ability to experience pleasure, and a fundamental sadness, which may be accompanied by irritability, sleep disturbances and anxiety. Depression can cause deficits in child development, poor academic achievement and teenage suicide. If untreated, pediatric depression can lead to more severe psychiatric disorders in later life, failure to succeed, and serious consequences for society.

Incidence

Depression affects 0.9% of preschool children, 2.5% of school-age children and 5% of adolescents in the United States.(f.1,2,3) An ongoing Canadian study following 23,000 children from birth to 11 years of age, and then on into adulthood, has found that 26% of the children suffer from academic, emotional, behavioural or social problems.(f.4) These problems include psychiatric and mood disorders such as depression.

The Ontario Child Health Study looked at the six-month prevalence of four child psychiatric disorders: conduct disorder, hyperactivity, emotional disorder and somatization. It found that 18% of children aged four to 16 years had one or more of these disorders.(f.5)

Impact of Depression on Child Life

Children with depression are at high risk for a variety of other psychiatric disorders and other dysfunctions. Studies have shown the following:

- There is a definite relationship between mood disorders and learning disabilities.(f.1,2,4,5,6,7) Children with learning disabilities have a greater incidence of mood disorders, the most common one being affective disorder.(f.6) Depression lowers school performance by reducing self-confidence, by causing children to be preoccupied with their inner worries, and by reducing their ability to concentrate. In the Ontario Child Health Study, children with a psychiatric disorder were found to use special education services 1.8 times more frequently than children without the disorder.(f.5) Several studies have shown that depression can affect school performance, and long-term depression may result in permanent deficits in child and social development and poor academic achievement.(f.1,6,7)

- Children with a history of depression are at a very high risk for developing recurrent episodes.(f.1,2,7)

- Prepubertal-onset depression is more severe, more resistant to treatment and increases the risk for development of bipolar disorder or manic-depression.(f.1)

- Children with depression have a much higher incidence of concurrent psychiatric disorders, e.g., anxiety disorder, attention deficit disorder, conduct disorders and bipolar disorders.(f.1,2,7) These comorbidities are suggestive of an underlying genetic and neurochemical connection.

- Suicide is the second leading cause of death in 10- to 19-year olds in Canada and the United States, accounting for 13% of deaths in boys and 7% in girls in the 10 to 14 age group.(f.1,8,9) This rate has doubled over the last 30 years, while the suicide rate for adolescent males has increased fourfold since 1960.(f.4,8,9)

- Canada's youth suicide rate is the third highest in the world.(f.4)

Clinical Presentation

Symptoms of depression are considered to be similar in children and adults, but are manifested differently in children. Therefore, criteria specific for pediatric depression have been developed.(f.1,6) The Weinberg Criteria describe the following symptoms of pediatric depression:

Depressed Mood: demonstrated by sadness, loneliness, mood swings, hypersensitivity, negative attitude, and irritability (very prominent in children).

Self-Deprecatory Ideation: feeling worthless, dumb, stupid, ugly or guilty, having low self-esteem, death wishes, suicidal thoughts and suicide attempts.

Aggressive Behaviour (Agitation): fighting, lack of respect for authority, difficulty getting along with others.

Sleep Disturbance: include initial, middle, & terminal insomnia, trouble awakening in the morning, hypersomnolence with daytime naps.

Change in School Performance: daydreaming, trouble concentrating, loss of interest in school activities, incomplete schoolwork resulting in lowered grades

Diminished Socialization: decreased group participation, withdrawal from friends, loss of social interest and pleasure. In teens, this can be seen in changing to a less desirable peer group.

Change in Attitude Toward School: can present with school refusal, due to loss of interest or inability to go to school in the morning when the child is the most depressed.

Somatic Complaints: nonspecific headaches, stomach aches, fatigue, nonspecific aches and pains. This common symptom of depression in children is not usually seen in adults, but may be the only presenting symptom in children

Loss of Usual Energy: complaints of physical or mental fatigue or boredom in usual activities

Change in Appetite and/or Weight: Absence of usual weight gain rather than weight loss, is more commonly seen in children. Excessive weight gain can be seen in children and teens, but teens frequently lose weight.(f.6)

Types of Depression

In major depression, several symptoms of depression must be present, causing significant mood disturbance at least half the time. Major depression occurs in episodes, lasting at least two weeks, with full or partial recovery in between. During these episodes, the child is severely dysfunctional.

Minor depression has fewer symptoms or episodes of shorter duration, with less dysfunction. These episodes can occur independently or can lead to major depression.

Dysthymic disorder is less intense than major depression, but is manifested by a depressed or irritable mood for at least one year, with no prolonged well states. The child may experience good and bad days, or frequent mixed days, but no good weeks. Many will develop a superimposed major depression, called "double depression". Because of its chronic nature, dysthymic disorder can be very disruptive to normal development.(f.6)

Risk Factors

Family History

A positive family history of major depression results in a three-fold increased incidence of developing pediatric depression, an earlier age of onset (< 20 years) and longer duration of illness.(f.1) Children with a major depression have a positive family history of mood disorders in 50% to 80% of cases.(f.2)

Environmental Factors

Depressed children tend to come from families with a higher incidence of daily stress, conflict, alcoholism, anxiety, negligence, abuse and psychiatric disorder, combined with less communication and support.(f.1,6)

Treatment

Treatment of depression is based on a careful assessment of psychological and social functioning and a medical examination. The goals of therapy are to manage the acute symptoms, and decrease the duration of the episode of depression to minimize dysfunction. Treatment is also focused on prevention of relapse and suicide. The child, family and school will be required to participate in treatment. Primary care physicians and pediatricians can play a major role in diagnosis and treatment of depression. However, any suicidal child should be referred to a psychiatrist. This is the one time when a health professional may break confidentiality to get help for the child. Hospitalization may be necessary to ensure the safety of children at risk for suicide. Depressed adolescents should be evaluated for substance abuse. Treatment of depression in children responds best to a combination of psychotherapy and antidepressants.(f.1,6)

Even though the efficacy of tricyclic antidepressants for major depression in adults is well established, there are only a handful of double-blind, placebo-controlled studies of tricyclics in children. Theses studies have shown response rates of greater than 50% for both antidepressants and placebo.(f.1,3,6,10) These inconclusive results are postulated to be due to the small number of study patients, study design, factors which may be unique to pediatric depression and could affect response to the medication, or the fact that pediatric depression responds to multiple interventions including placebo trials.(f.10)

Choice of drug depends on the side-effect profile (i.e., using amitriptyline in children with insomnia, or desipramine to minimize daytime sedation and in overweight children.(f.6,11) Amitriptyline and imipramine are started at 1-2 mg/kg/24 hrs up to 5 mg/kg/24 hrs in divided doses. Therapeutic serum levels are 150-300 ng/mL for the combined levels of drug and primary metabolites (nortriptyline & desipramine). For nortriptyline and desipramine, the levels are 50-150 ng/mL. Serum levels are taken in this age group to check for compliance and identify fast metabolizers.(f.6) Doxepin has the same dosage range and side effect profile as amitriptyline. Use of tricyclics in the pediatric population is limited by anticholinergic and cardiac side effects.(f.1,3,6,10) Due to the potential for overdosage with tricyclics, it is recommended that they be dispensed in small quantities and administered under supervision.

Monoamine oxidase inhibitors are not recommended for use in children because of side effects and dietary restrictions. Lithium can enhance response to tricyclics in some cases.(f.1,10,11)

Recent studies have found some of the selective serotonin reuptake inhibitors (SSRIs) to be safe and effective in this age group.(f.1,2,3,6,11) The rationale for use of SSRIs in management of childhood depression are:

- the safety profile of SSRIs is superior to tricyclics (i.e., cardiac side effects and anicholinergic effects)

- SSRIs do not require therapeutic drug monitoring as is recommended with tricyclics

- SSRIs are less toxic in overdoses than tricyclics, so are safer in suicidal children(f.2,11)

- SSRIs have fewer side effects in children than tricyclics, the main ones being insomnia and nausea.

Fluoxetine and paroxetine are usually started at half the minimum adult dose (i.e., 10mg/24 hrs. qam). Therapeutic serum levels of fluoxetine and norfloxetine should be above 300 ng/mL.(f.6)

Maximum benefits with antidepressants are seen after eight to 10 weeks of treatment, although there is no accepted duration of therapy in children. Based on adult results and clinical experience with teenagers, continued treatment for five to six months after remission of depression is appropriate.(f.11)

A recent study of sertraline in 29 children and 32 adolescents with major depression and/or obsessive-compulsive disorder found that the pharmacokinetic profile of sertraline and its major metabolite in pediatric patients was similar to that established in adults. The same dosage as adults, of 50 mg once daily initially, with upward titration of 50 mg weekly to a maximum of 200 mg/day was found to be safe and effective in children. The side effects were mild to moderate, consisting of headache, nausea, insomnia, somnolence, dyspepsia, and anorexia.(f.2)

A case study of nefazodone also found improvement in a small group of children with very severe and treatment-resistant depression. The dosing was started at 50 mg daily and titrated upward at three- to seven-day intervals in a bid dosing until a clinical effect or adverse effect emerged, averaging a dose of 3.4 mg/kg/24 hrs. The study concluded that nefazodone may be a treatment option for juveniles with mood disorders.(f.3)

Even though these studies show encouraging results, more studies with larger patient populations are needed before therapy with SSRIs has an established place in treatment of childhood depression.

Pediatric depression is a serious medical problem that can affect child development, academic achievement, and can cause suicide. Pharmacists should be aware of the symptoms and treatment of this disorder so they can be a good resource for families, schools and communities.

References

(f.1) Jelinek MS., Snyder JB. Depression and Suicide in Children and Adolescents, Pediatrics in Review 1998; 19(8): 255-64.

(f.2) Alderman J, Wolkow R.,Chung M, et al. Sertraline Treatment of Children and Adolescents With Obsessive-Compulsive Disorder or Depression: Pharmacokinetics, Tolerability, and Efficacy, J Am Acad Child Adolesc Psychiatry, 1998; 37(4): 386-94.

(f.3) Wilens TE., Spencer T J, Biederman J et al, Case Study: Nefazodone for Juvenile Mood Disorders, J Am Acad Child Adolesc Psychiatry, 1997; 36(4): 481-85.

(f.4) Steinhauer PD, How Paediatricians Can Improve Developmental Outcomes for Children, Paediatr Child Health 1997; 2(6): 393-97.

(f.5) Offord D R., Boyle M H., Szatmari P. et al, Ontario Child Health Study, II. Six-Month Prevalence of Disorder and Rates of Service Utilization, Arch Gen Psychiatry 1987; 44: 832-36.

(f.6) Emslie G J., Kennard B D, Kowatch R A, Affective Disorders in Children: Diagnosis and Management, J Child Neurology 1995; 10(suppl 1): S42-S49.

(f.7) Kovacs M, Goldston D, Cognitive and Social Cognitive Development of Depressed Children and Adolescents, J Am Acad Child Adolesc Psychiatry 1991; 30(3): 388-92.

(f.8) Ohlsson A, Lacy J B, The Health of Canada's Children, Paediatr Child Health 1996; 1(1): 78-80.

(f.9) Haslam RHA, The State of Canadian Children's Health, Paediatr Child Health 1997; 2(2): 125-27.

(f.10) Kye C, Ryan N, Pharmacologic Treatment of Child and Adolescent Depression, Child and Adolescent Psychiatric Clinics of North America 1995; 4(2): 261-81.

(f.11) Ambrosini PJ, Bianchi MD, Rabinovich H et al., SPECIAL ARTICLE, Antidepressants Treatments in Children and Adolescents I. Affective Disorders, J Am Acad Child Adolesc Psychiatry, 1993; 32(1): 1-6.

DIFFERENTIAL DIAGNOSIS

Pediatric depression is very difficult to diagnose, especially in the young child. Children with chronic illness or psychiatric disorders often manifest concurrent depression, which complicates management. The following conditions should be considered before making a positive diagnosis:

Infectious Diseases: mononucleosis, influenza, encephalitis, pneumonia, tuberculosis, hepatitis, syphilis, AIDS.

Endocrine disorders: diabetes, Cushing disease, hypothyroidism, hyperthyroidism, hypopituitarism, hyperparathyroidism, Addison disease.

Neuro/tumor: epilepsy, post-concussion, brain hemorrhage or stroke, multilpe sclerosis, Huntington disease.

Effects of Medications: antihy-pertensives, barbiturates, benzodiazepines, corticosteroids, oral contraceptives, cimetidine, aminophylline, anticonvulsants, clonidine, digitalis, thiazide diuretics.

Others: alcohol and drug abuse, electrolyte abnormalities, anemia, lupus, Wilson disease, porphyria, uremia.(f.1)