Summary

Depression affects about 2% of children and 4% to 8% of adolescents. The clinical features of the disorder in the paediatric age group are quite similar to those of the adults', with symptoms of depressed mood, biological symptoms and depressive cognition. If untreated, it may lead to suicidal behaviour and serious disruption in psychosocial functioning. There has been increasing evidence on the efficacy of psychological interventions in treating childhood and adolescent depression. The use of antidepressant treatment has been more controversial because of the safety efficacy profile for some medications.

摘要

據估計約有百分之二的兒童及百分之四至八的青少年患上抑鬱症，臨床病徵與成年病人的十分相似，包括情緒抑鬱、生理症狀及抑鬱性思想。若不受治療，可導致自殺及嚴重心理社交失衡。更多證據顯示心理治療對兒童及青少年抑鬱症相當有效，而抗抑鬱藥治療法，由於其安全性及有效性而較受爭議。

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Introduction

It used to be widely believed that adult type of depression did not occur in childhood. In the past two decades, there has been emerging evidence supporting the prevalence of the condition in childhood and adolescence.

Epidemiology

Depression is a common condition among adults, with lifetime prevalence of about 15%. Population studies of children and adolescents have reported prevalence rates of depression to be about 2% among children and about 4% to 8% among adolescents.^1,2 Depression in childhood remains uncommon. When puberty begins, the rate of depression increases sharply. While depression is more common among women in adults, it has a similar prevalence among prepubertal boys and girls. With the beginning of puberty, the rate among adolescent girls exceeds that of adolescent boys. The female-to-male ratio approaches 2:1 in adolescence.^1,3 The change in gender ratio has been attributed to various factors including genetics, biological changes associated with puberty, sociocultural factors and cognitive factors.

Clinical features

Depressed mood is the cardinal symptom of depression. However, the symptom of depression is not synonymous with sadness or unhappiness.^4,5 Depressed mood is more pervasive. The low mood is present most time of the day and most days of the week, and is commonly associated with anhedonia _ lack of enjoyment. Anhedonic individuals are unable to experience pleasure. Children and adolescents who present with a recent failure to take pleasure in activities that they used to enjoy, e.g. computer games, going out with friends, for several weeks or even months should alarm clinicians to look for the presence of any mental disorder. Nevertheless, irritable mood may be present in some patients instead of depressed mood. Biological symptoms, with insomnia and weight loss (or failure to gain weight) in particular, are also sensitive indicators of mental health problems among children and adolescents. However, it is important to distinguish insomnia from sleep habit problems. Adolescents with sleep habit problems usually have sufficient amount of sleep but at irregular hours. For example, not uncommonly do we encounter adolescents who go to sleep at 3am and wake up at 11am. Certainly they have difficulty in getting off to sleep at 10pm because their sleep wake cycle is disturbed. Depressive cognition is another core symptom of depression. Children have negative views of the past, present and future, and hence feel guilty for what they did, feel useless and then feel hopeless towards the future. Younger children may have less cognitive symptoms in relation to their cognitive immaturity. Although there is no clear demarcation on the severity of depression, the presence of suicidal ideation, prominent biological symptoms or significant impairment in functioning usually denote moderate to severe depression.

According to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, (DSM-IV),⁶ the most commonly used diagnostic manual for psychiatric disorders, the depressed mood should be present for at least 2 weeks before depression can be diagnosed. For most depressed children and adolescents, they often suffer from the depressed mood for months. Table 1 listed the DSM-IV criteria for the diagnosis of depression. In severe depression, there may be mood congruent psychotic symptoms. It is clear from the above description that children and adolescents suffering from depression have similar clinical manifestations as the adult disorder. However, there may be some variations in clinical presentations because of different levels of development. Biological symptoms are usually more prominent in adolescents and adults. Suicide, suicide attempts and psychotic symptoms are rare among prepubertal children. On the other hand, phobias, separation anxiety and somatic complaints may be present in depressed children.⁷

Differential diagnosis and comorbidity

Substance misuse is an important differential diagnosis for major depression in children and adolescents. Withdrawal states of stimulants such as amphetamine may present with depression and suicidal tendency. Eating disorder, an increasingly common condition among adolescent girls, should also be considered, as depressive symptoms quite commonly occur in these patients. Medical disorders such as hypothyroidism should be ruled out as their symptoms may mimic those of depressive disorder. Neurological conditions such as Wilson's disease, systemic lupus erythematosis, HIV infection, though rare, may present with depression or other psychiatric symptoms. Concurrent medication as a cause of depression should also be excluded.

Depression commonly co-exists with other psychiatric diagnoses in children and adolescents. Forty percent to 70% of depressed children and adolescents have at least one comorbid disorder, anxiety disorder being the commonest.⁷ Other common comorbid disorders include dysthymia (a minor form of depressive disorder with more prolonged but less severe symptoms), disruptive behavioural disorders and substance misuse.

Natural course and sequelae

The mean length of an episode of major depression is approximately 7 to 9 months in children and adolescents.⁷ About 90% remit by 1.5 to 2 years after the onset, with about 6% to 10% becoming protracted.⁶ Longitudinal studies have shown that major depression in children and adolescents is a recurrent condition^3,8,9 and persisted into adulthood,¹⁰ with estimation of recurrence rates to be 60% to 70%. Follow up studies have found that 20% to 40% of adolescent major depression subsequently develop bipolar affective disorder at 5 years. Bipolar disorder is characterized by episodes of mania (see Table 2 for DSM-IV clinical features of mania) and depression. Children and adolescents whose depressive disorders are accompanied by psychotic symptoms are at increased risk of developing bipolar disorder.

Although most depressive disorders remit after 1 to 2 years, it is important to recognize and treat the condition early to prevent the occurrence of complications and undesirable sequelae. Suicide and suicide attempts may punctuate the course of depression. In cross sectional studies of children and adolescents with depression, one third to two thirds of subjects reported suicidal tendency.^11,12 During the episode of depression, the individual may underachieve or drop out from the school system. He/She may be disengaged from the social circle. If the young person's difficulty is not recognized and understood by family, the above psychosocial disengagement can lead to escalating conflicts and tension in the parent - child relationship, which can further worsen the depressive symptoms.

Aetiology

Genetic factors

Twins and adoption studies have shown that genetic factors accounted for about 50% of variance in the transmission of depressive disorders and up to 80% of variance in bipolar disorders in young people.^13,14 On the other hand, these studies highlight the importance of environmental factors in depressive disorders. Individuals who have the genetic predisposition appear to be at higher risk upon exposure to the environmental risk factors, when compared with those with less genetic predisposition. Children of depressed parents have been estimated to have a 15% to 45% lifetime prevalence of major depression.^15,16

Psychosocial factors

Studies of depressed youths and children of depressed parents suggested presence of more family conflicts, rejection, abuse, communication problems, less expression of affect and support when compared with family interactions of normal controls.¹⁷ However, one must be cautious that these factors are not unique to the depressive disorder. These kinds of family interaction patterns are also prevalent among other childhood psychiatric disorder such as conduct disorder. It is also possible that these interaction patterns are a result of coping to the child's psychopathology, particularly in families with conduct disordered children.

Psychological factors

There have been hypotheses that individuals with negative cognitive styles, i.e. a negative view of themselves, of the world and of the future, predispose them to depressive disorder. However, it has been unclear whether this is a cause or consequence of depression. Several longitudinal studies have shown that the negative cognitive style actually precede the occurrence of depressive symptoms.^18,19 Conversely, some studies looking into depressive disorders among young people have shown the negative attributional style being state-dependent, i.e. the negative cognitive style disappeared upon resolution of the depression.²⁰

Biological factors

Several neurotransmitter systems such as serotoninergic, adrenergic systems have been implicated in the pathophysiology of depression in adults. These kinds of studies in children and adolescents have been scarce. One study has shown significantly lower cortisol level after L-5-hydroxytryptaphan infusion among depressed children when compared with normal controls.²¹ Evidence in relation to the hypothalamic-pituitary-adrenal axis has been inconsistent.

In summary, the aetiology of depression in childhood and adolescent depression, like other adult psychiatric disorders, is the result of a complex interplay of genetic and environmental factors.

Assessment

Information from multiple sources is always essential in the assessment of psychiatric conditions in children and adolescents. This includes interviews with the child or adolescent alone, interviews with the parents, and collateral sources of information such as school, peers, other professionals and direct observation. Internalizing symptoms, such as depressive and anxiety symptoms are better reported by the young people themselves, while externalizing symptoms such as behavioural problems are better reported by parents. Young people are reluctant to discuss issues such as substance misuse, sexual experience in front of their parents. On the contrary, family interaction patterns such as overprotection, dominance and parental anxiety are more evident during conjoint interview. The assessment involves a thorough examination of the depressive symptomatology, current stressors, family dynamics and the presence of comorbid conditions. The assessment of current stressors such as learning difficulties, peer relationship problems, family discord, physical and sexual abuse are particularly pertinent. Medical disorders should be ruled out. Questionnaires such as the Beck Depression Inventory²² and the Children's Depression Inventory²³ have been used in the assessment of child and adolescent depression, but they are more often used for the screening of depressive symptoms, measuring the severity and monitoring the change of symptoms rather than diagnosis because of low specificity of the instruments. Structured interviews,^24,25 usually quite long and tedious to administer, are generally used in research rather than in the clinical setting.

Treatment

Acute treatment

Both pharmacological and psychological interventions have been used in the treatment of depression in children and adolescents. For milder forms of depression with clearly identifiable stressors such as examination stress, family discord, the manipulation of the social environment (such as the removal of the ongoing stress), support from the family and the professionals may already lead to improvement in symptoms. For moderate to severe disorders, additional treatments are usually needed and will be discussed below. Education of the patient and family about the disorder is also essential as parents may have misunderstanding of the child's or adolescent's symptoms. For example, lack of energy and interest may be construed as "laziness".

There is robust evidence on the effectiveness of psychological interventions in treating adult depression. Over the past decade, there has been increasing data on their efficacy on treating the condition in children and adolescents. Cognitive behavioural therapy (CBT) has the most established efficacy amongst the various psychological treatments.^26,27 CBT aims at challenging maladaptive and negative thoughts in the depressed individual. It was designed based on the theory that depressed individual had a distorted negative view of the world, the development of which is related to earlier adversity. When the child encounters current difficulties, these negative thoughts are triggered and lead to depressive symptoms. CBT is structured and time limited, the therapist and the young person have a collaborative relationship, working together to solve problems. Apart from cognitive and behavioural strategies used in CBT for adult depression, a variety of other components such as problem solving skills, coping skills, communication skills, positive self-talk, social skills training, anger management and relaxation skills are sometimes incorporated. In general, behavioural techniques may be more useful in children while cognitive techniques may be more helpful in adolescents, in relation to their level of cognitive maturity. Studies have reported 50% to 60% of depressed young people improve with CBT.^26,28 CBT has also been found to be superior to family therapy and supportive therapy, with better clinical recovery and more rapid relief of depressive symptoms.²⁹ The World Psychiatric Association has published a manual on CBT for children and adolescents for clinician's reference.³⁰ Interpersonal psychotherapy (IPT), another time limited psychotherapy focusing on current interpersonal problems, has been shown to be effective in reducing symptoms for depressed adolescents as well.³¹ IPT is a time-limited psychotherapy that focuses on current problems. It was developed based on the principle that depression occurs in the context of interpersonal relationships. The goals of IPT are to reduce depressive symptoms and improve interpersonal functioning by relating the symptoms to one or more of four problem areas, namely grief, role disputes, role transitions and interpersonal deficits. Last but not the least, family therapy, which targets dysfunctional family dynamics, is another treatment of choice. However, there have only been a few studies and the evidence thus far has been negative. Its efficacy waits to be sufficiently tested.

Pharmacological treatment of depressed children and adolescents has long aroused controversy in the mental health arena. First, the efficacy of tricyclic antidepressants (TCA) was in doubt, its cardiovascular side effect has also been a concern. Second, past data have shown an elevated risk of suicidal behaviour among children and adolescents taking serotonin reuptake inhibitors and other newer antidepressants.³² Therefore, to determine the use and choice of antidepressants in child and adolescent depression, the efficacy and adverse effects of the medications should be fully appreciated.

Tricyclic antidepressant

There have been limited number of drug trials on the use of TCA in childhood and adolescent depression. Besides, many have been open trials and involved a small number of subjects. The Cochrane database has reviewed the efficacy of TCA in childhood and adolescent depression and has concluded that TCAs are not useful in childhood depression, while there is marginal evidence to support the use of TCAs in the treatment of adolescent depression.³³ It is essential to note that there is often a high placebo response rate in these trials, sometimes up to 30% to 40%. TCAs have been found to have significantly more vertigo, orthostatic hypotension, tremor and dry mouth when compared with placebo. Compared with adults, doses required for young people are higher in terms of mg/kg because of more extensive metabolism. TCAs are also more cardiotoxic in young people and the co-administration of other drugs known to prolong QTc should be avoided.

Serotonin reuptake inhibitors

Open studies have reported response rates of 70% to 90% to the serotonin reuptake inhibitors (SSRI) for the treatment of adolescent depression.² There have been several controlled trials on various SSRIs and other newer antidepressants. Again, these studies usually include a small number of subjects, have methodological problems and the placebo response rates are quite high (>30%). In 2004, a major study, Treatment for Adolescents with Depression Study (TADS), has been published, comparing the efficacy of fluoxetine, CBT, fluoxetine combined with CBT, and placebo. This is an important study as it has recruited over 400 subjects with rigorous methodology. More importantly, it has been funded by the National Institute of Mental Health rather than by drug companies. The study has found that the response rates of fluoxetine combined with CBT (71%) was superior to fluoxetine alone (61%), CBT alone (43%) and placebo (35%) in reducing depressive symptoms. Fluoxetine alone is also superior to CBT or placebo in the reduction of depressive symptoms.²⁷ In addition, CBT seems to have a specific benefit on suicidality. This is a landmark study establishing the efficacy of fluoxetine in the treatment of adolescent depression.

Despite the positive evidence, there is also the downside of using SSRIs in childhood and adolescent depression. In 2003, upon reviewing the paediatric drug trial data of paroxetine (one of the commonly prescribed SSRIs), the US Food and Drug Administration (FDA) was concerned about the safety data and requested the submission of report and data from the drug companies, which had conducted paediatric antidepressant trials. An external panel has been commissioned to review the safety data. The analysis has shown an elevated risk of suicidal behaviour (suicidal idea and suicide attempt) among children and adolescents taking SSRIs and other new antidepressants when compared with placebo. The overall risk difference is about 2%.³² There was no completed suicide in the trials.

Consequently, risks and benefits should be carefully balanced before embarking on the use of antidepressants in this age group. In a risk benefit analysis of randomized controlled trials of SSRIs and new antidepressants, it has been found that only fluoxetine shows a favourable risk-benefit profile for the treatment of child and adolescent depression, while the data for the other antidepressants in the study have been unfavourable.³⁴ As a result of all the above findings, the UK National Institute of Health and Clinical Excellence (NICE) has recently issued a guideline on the treatment of childhood and adolescent depression. NICE recommends that psychological interventions should always be the first line treatment. If these fail, fluoxetine will be considered, in combination with psychological treatments. The use of antidepressants in childhood depression (5-11 years old) should be particularly cautious, as their effectiveness has not been established for this age group. Table 3 has summarized the NICE guideline.³⁵

In the local setting, psychological interventions are not widely available because of limited expertise and enormous case load. However, psychological intervention should still be considered a first line treatment whenever possible. Management of concurrent psychosocial stressors and psychoeducation to patient and family are also crucial. Thus far, none of the SSRIs or newer antidepressants has been approved for treating childhood and adolescent depression in Hong Kong. The decision on the use of antidepressants to treat youth depression should therefore be made after careful balance of risks and benefits, and is best performed by clinicians with experience and knowledge in paediatric psychopathology and psychopharmacology, as recommended by the Hong Kong College of Psychiatrists.³⁶ As mentioned above, the use of antidepressants in childhood depression (5-11 years old) should be exceptionally judicious.

Maintenance and continuation treatment

In adults, both psychotherapy and antidepressant treatment have been found to be useful in reducing relapse of major depressive disorder.³⁷ In children and adolescents, continuation of antidepressant for at least 6 months after remission is recommended, in view of the high rate of relapse and recurrence.^2,35 The guideline on continuation therapy of psychological intervention is less clear. The data addressing the long term benefits of CBT for adolescent depression have been mixed. In general, studies with relatively short term follow up (1 to 9 months) have shown that post-treatment gains are usually maintained. Nevertheless, studies with longer follow up period (9 months to 2 years) have found a significant proportion of subjects continue to report depressive symptoms or experience a recurrence of their depressive illness.³⁸ Therefore, continuation therapy such as booster sessions may be useful. There have been some data that monthly CBT session in the post treatment phase may be helpful in reducing relapse of depression in adolescents.³⁹

Conclusion

Depression is a major morbidity in children and adolescents. Early recognition and treatment are essential. Treatment starts with a thorough biopsychosocial assessment and the choice of treatment modality depends on the severity of symptoms and the illness profile.

Key messages

1. Depression in children and adolescents often show similar clinical features as adult depression.
2. The assessment of children and adolescents with depression should include a detailed assessment of the symptoms, current psychosocial stressors, substance misuse and concurrent medical conditions.
3. Mild depressive disorders in children and adolescents should be managed by modification of the stressors and social environment and non-directive supportive psychotherapy.
4. Moderate to severe depression in children and adolescents should be treated by psychological interventions as first line. If psychological interventions are not available or not effective, then fluoxetine should be considered.
5. Antidepressant use in children and adolescents should be performed by clinicians experienced in paediatric psychopathology and psychopharmacology. Patient and relatives should be fully informed of potential risks and benefits, including the risk of increased suicidal behaviour.

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References