Making the diagnosis of a depressive disorder in pediatric patients can be challenging, even in the absence of a seizure disorder. A common mistake made by busy clinicians is to miss a diagnosis of a depressive disorder when no blatant behavioral difficulties are present. Symptoms that should alert the clinician include a decline in academic functioning, withdrawal from friends, or lack of pleasure from previously enjoyable activities. Children often deny such symptoms and may not express depressive ideas spontaneously; instead they may have multiple somatic complaints. Parents may be far less attuned to their child’s internal mood state than overt behavioral problems, and they may be preoccupied by worries about the child’s epilepsy. Although childhood self-report measures, such as the Children’s Depression Inventory (CDI) (32,33), can be
valuable in identifying and tracking symptoms of depression over time, self-report measures are not, in themselves, reliable measures with which to diagnose a depressive disorder. These measures are discussed in further detail in Chapter 8.

A complete psychiatric evaluation is required to establish a diagnosis of depression. It is also critical to obtain a detailed family history to elicit the presence of genetic factors, that is, evidence of other family members who have been depressed or who have had other psychiatric problems. A complete medical examination is indicated to rule out underlying physical conditions that may present as depression. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (34), specific diagnostic criteria must be present to make the diagnosis of major depression. However, these criteria emphasize symptoms noted in adults rather than children. For example, pediatric patients do not tend to present with the vegetative symptoms of depression, such as lack of appetite or sleep disturbance. Alternatively, depressed children and adolescents may be more likely to dwell on distorted, negative views of themselves, their life, friends, and family.

Dysthymic disorder is a syndrome distinct from major depression, characterized by milder depressive symptoms persisting over a year (in adults, a period of 2 years is required). However, it is a mistake to think of this as a relatively benign disorder in childhood; dysthymia is a chronic depressive disorder associated with potentially significant psychiatric morbidity (35,36,37). In this condition, a child or an adolescent is never symptom-free for more than 2 months. Furthermore, dysthymia may also be a gateway to other mood disorders.

Major depressive disorder is uncommon in childhood and more frequent in the adolescent population. Reported rates of depression are contingent on whether symptoms or a syndrome of depression was measured and dependent on the specific subgroup examined. Overall, major depression is rare in preschool children, has a frequency of approximately 2% in children of elementary school age, and approximately 5% in adolescents. Boys and girls have equal rates before puberty, but in adolescence, girls have higher rates of depression (35). Many investigations suggest that adult patients with epilepsy (especially those with intractable seizures) are at particularly high risk for developing symptoms of depression (38,39). For example, at one university-based epilepsy center, more than 50% of adult patients had elevated depressive symptom scores on self-report measures (40). Although such studies have heightened clinician awareness of the problem in adults, few investigations have examined this issue in children and adolescents.

In our pediatric series (6), 26% of children and adolescents with epilepsy had significantly elevated depression scores on the CDI. None of these children had been previously identified to be depressed, and none had ever received a psychiatric evaluation or treatment, suggesting that depression and anxiety may be substantially under-recognized in this population. Similarly, Dunn et al. (41) found that 23% of adolescents with epilepsy had symptoms of depression. The strongest predictors of depression were a negative attitude toward illness, dissatisfaction with family relationships, and unknown or external locus of control (a feeling of lack of control over one’s life and destiny) (41). Table 9.3 shows the salient depression frequency studies.

A child can have a significant depressive disorder where symptoms of irritability are much more prominent than depressive symptoms. Furthermore, young patients often carry more than one psychiatric diagnosis. For example, it is not uncommon to see a child who has a diagnoses of attention-deficit hyperactivity disorder (ADHD), a depressive disorder, and a receptive/expressive language disorder. The lack of specificity of symptoms associated with depression in pediatric age-groups and the overlap of these symptoms in other psychiatric disorders makes the diagnosis of depressive disorder quite challenging in this population. This diagnostic dilemma is shown in Table 9.4.

One quick way to recall the warning signs of depression in children and adolescents, with or without epilepsy, is to remember the acronym “D.U.M.P.S (G. Carlson, private communication). D stands for “definite personality change” (e.g., a youth who had previously been a good student or had a nice disposition suddenly or gradually becomes defiant, disagreeable, distant, or disorganized). U represents “undeniable drop in grades” (e.g., a youth whose grades decline from A’s to C’s over the course of a semester or who avoids school together or develops a “school phobia” or social anxiety. M stands for “morbid preoccupation” (e.g., a youth whose compositions dwell upon death and disaster or who voices suicidal thoughts or who engages in self-destructive behaviors). P stands for “pessimism or psychosis” (e.g., a youth
who is grim, depressed-appearing, demoralized and who sees no joy in anything). Psychotic symptoms would include acute onset of depression-related hallucinations and/or delusions. Finally, S indicates “somatic complaints without physical basis” (e.g., a youth who spends more time in the nurse’s office than in the classroom, complaining of headaches, abdominal pain or fatigue, without obvious physiological cause).

The potential role of AEDs in depressive symptomatology is discussed in the following text. Other potential etiologies for mood disorders in children and adolescents are shown in Table 9.5.

It is incumbent on the physician who suspects depression to inquire about suicidal ideation. Some physicians concerned about lack of access to a child and adolescent psychiatrist may avoid even asking about self-destructive thoughts and/or behaviors; this is not an acceptable solution. Even if a skilled psychiatric clinician is unavailable, a child or an adolescent can always be sent to the emergency room for evaluation. Suicidal ideation is considered a potential psychiatric emergency and such a referral is quite appropriate. Suicide attempts among patients with epilepsy are estimated to occur at two to seven times the rate in the general population (50,51). Conversely, epilepsy was the most frequent medical condition found among a group of pediatric patients evaluated for suicide attempts at one center (48).

Few studies have examined suicidal ideation in the pediatric epilepsy population. In our series discussed earlier, we found 4.3% with intent and 11% without intent. Ott et al. (42) found among 48 patients with CP seizures, suicidal ideation in 17% and intent in 8%, with 18% ideation and 11% intent among 39 cases of chronic absence epilepsy. However, these rates were not significantly higher than in a normal control group.

Making the diagnosis of bipolar disorder in children and adolescents is one of the most challenging diagnostic tasks in child and adolescent psychiatry. These days, the diagnosis
of bipolar disorder has become quite “popular” and children with symptoms of rages and emotional dysregulation are frequently given this diagnosis when it is not clearly justified (52). Bipolar disorder is often confused with ADHD), and its presentation may be complicated by a number of other comorbid conditions. Classic bipolar disorder is uncommon in childhood although it clearly does occur, rarely. In the adolescent and adult population, bipolar disorder has been estimated to occur at a rate of approximately 0.6% to 1% (53). In children and adolescents with epilepsy, little is known about the frequency of manic symptoms. A recent study from our center found bipolar symptomatology in 12.2% of community-based adults with epilepsy; (54) however, additional studies are currently under way to assess whether these symptoms translate into a formal diagnosis and to look at the rates of bipolar symptoms in adolescents with epilepsy.

Treatment of childhood depression should include parental and teacher involvement, in addition to directing attention to the child. Psychotherapy, including parental guidance sessions and family therapy, as well as individual sessions for the child, should be strongly considered. Recently, much emphasis has been placed on cognitive-behavioral approaches (55) and interpersonal therapy techniques. Interventions related to the school environment, such as reducing academic pressures by providing educational accommodations and more academic supports, are often crucial. Often, depressed children and adolescents miss many days of school and fall behind in their schoolwork, so that individual tutoring may be needed. It is not unusual to find symptoms of school phobia or social phobia emerging in this context. The simplistic, knee-jerk response of writing a prescription for home tutoring can often prolong and intensify symptoms of anxiety and depression.

Depending on symptom severity, the degree of functional impairment, and the history of prior treatment attempts, a child and adolescent psychiatrist will consider prescribing an antidepressant. Inpatient psychiatric evaluation may be required in the presence of suicidal ideation or attempts, dangerous behaviors, or severe side effects from previous medication trials. Psychoeducation of patient and family is critical because the decision to use medication for the treatment of depression is a complex one that requires a high level of collaboration and cooperation by parents and child.

The use of antidepressants in children and adolescents is currently an active area of research, controversy, and intense media scrutiny (56). Although published randomized, controlled medication trials suggested that antidepressants are efficacious in the treatment of depression in pediatric populations, a significant amount of data was unpublished and did not sufficiently demonstrate a positive treatment response. In the vast majority of these studies, the placebo response rates were extraordinarily high (ranging from 50% to 73%) in these industry-sponsored trials. The same poor response was found in double-blind, placebo-controlled studies of tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) (57,58). In addition to high placebo response rates, other problems included limited study observation periods and inclusion of patients with mild depressive symptoms rather than moderate to severely affected cases of major depressive episodes. In the case of the failed tricyclic studies, neurodevelopmental factors may have led prepubertal children to be less responsive than adults to norepinephrine-enhancing agents. Concerns regarding potential cardiac complications, including several cases of sudden death in prepubertal children, have steered many psychiatrists away from the use of tricyclic antidepressants. The SSRIs have become first-line antidepressants; however, the evidence of efficacy for most of these agents is still lacking. Outside of studies of fluoxetine, there was no further data leading to robust
evidence of efficacy of antidepressants in children and adolescents. Only fluoxetine has consistently demonstrated statistically significant efficacy in treating depression in children and adolescents in two placebo-controlled clinical trials (the minimum standard for U.S. Food and Drug Administration [FDA] approval) (59,60).

Although concerns about the possibility of antidepressants causing suicidality have always been present in adult patients (particularly as the immediate and most severe features of psychomotor retardation recede in the initial weeks of treatment), the issue of antidepressant-related suicidality in children and adolescents has only recently become an area of intense focus and concern (61,62). In 2002, concerns were raised at the FDA and the British medical health care regulatory agency about the possible emergence of suicidality in association with antidepressant use in pediatric patients and adults. After an extensive period of study, the FDA concluded that there is a low-magnitude, low-frequency suicide (ideation or behavior) signal in the adverse events/serious adverse events data set of all antidepressants. It should be noted, however, that evaluation of systematically collected data on depression rating scales (suicide items) found no evidence of a suicide signal. Furthermore, no conclusive evidence of moderating or mediating factors leading to risk for suicidal adverse events was found. The “suicide signal” in the adverse event data was felt to be a class effect, that is, no drug in the antidepressant class is completely without risk of potential suicidality. The end result was a decision by the FDA to issue a black box warning for use in pediatric patients for all SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) currently available (63,64,65).

The bottom line is that evidence of emergent suicide-related events remains uncertain. The rates of suicide-related events are very low, and the relationship of these events to ultimate suicide is tenuous. In fact, the adverse events data stands in contrast to a recent decline in youth suicide correlating with increased antidepressant use by children and adolescents. A thorough analysis on the risks versus benefits of antidepressants for children and adolescents with depression was performed by Bridge et al. (61). In this analysis, the degree of treatment effect was computed using available data from SSRI trials related to drug–placebo difference in responses and drug–placebo difference in suicidality. They concluded that more than six times as many children and adolescents will respond positively to antidepressants as will have suicidal ideation or behavior. This study demonstrated that the risks of suicidal ideation or behavior are far outweighed by the benefits of antidepressant medication treatment.

Pragmatically speaking, clinicians need to do a very careful job of: (a) evaluating the child or adolescent, including assessing histories of suicidal behavior, (b) recording that information, and (c) informing families about the risks of treatment and the risks of withholding pharmacotherapy. During the first 12 to 16 weeks of treatment, any child or adolescent who is treated with an antidepressant—of any kind and for any reason—needs to be closely monitored. The FDA has published guidelines of recommended frequencies of visits to the treating physician that include weekly visits for the first 4 weeks followed by biweekly visits and subsequently monthly visits. The intensity of supervision and the time commitment has led many nonpsychiatric clinicians to reconsider the clinical and medicolegal feasibility of prescribing these medications at this time.

Excessive concern over the potential risk of antidepressant lowering of the seizure threshold may also inhibit the otherwise appropriate administration of these agents. An extensive discussion of this issue, which has been studied predominantly in adults, may be found in Chapter 13. Although seizure risk is believed to be elevated with antidepressants such as bupropion, clomipramine, and maprotiline, the risk of seizure-induction with SSRIs is low, and some research suggests even the possibility of antiepileptic benefits (66).

Anxiety may be defined as an emotional uneasiness associated with the anticipation of danger (67). Anxiety is felt to be a normal emotion throughout development and it is felt to play both a protective and on adaptive role (68). Transitory fears and isolated subclinical anxiety symptoms occur throughout childhood and adolescence, and are accepted as part of normal childhood development. However, the line between normal and abnormal anxiety is sometimes blurred. To define an abnormal degree of anxiety, it is necessary to consider the degree to which irrational fears or worries cause significant distress or impairment in academic or social functioning. Developmental factors are also significant, as some types of anxiety are normal at certain stages of childhood and not others, that is, separation anxiety. The differentiation of an anxiety disorder from problematic symptoms of anxiety is another complex issue, as children may not qualify for an anxiety disorder diagnosis, yet they still may be experiencing significantly distressing symptoms (68). In the case of children who have severe and/or chronic medical conditions such as epilepsy, children and their parents may be experiencing symptoms of a stress reaction, such as acute stress disorder (ASD) or chronic post-traumatic stress disorder (PTSD).

Unrecognized anxiety symptoms lead to further suffering of children and their families. Given the existence of effective psychotherapeutic and pharmacological interventions for anxiety (69) in this population, the need to identify such symptoms and disorders is even more compelling.

There are very few studies of anxiety in pediatric epilepsy. Clinical impression suggests that children and adolescents with epilepsy may be particularly prone to anxiety. The unpredictability of seizures, the fear of death, parental reactions of distress and fear, the stigma associated with epilepsy, and misinformation about the disorder may predispose children and adolescents to anxiety and negative affective responses (45).

Fear of dying or developing brain damage or mental retardation may also underlie anxiety symptoms (70). Social phobias may result from the extreme embarrassment of having seizures in public, particularly in school. This may be more common than is usually recognized in children or adolescents with seizure disorders. However, when symptoms of school refusal or social avoidance occur in children with epilepsy, it is important to remember this diagnostic possibility.

Parents of children with epilepsy have another set of anxieties different from their children’s fears. These anxieties may lead them to be overprotective or overindulgent of their children. This can promote a transmission of anxieties to their children. It is as important to work with the parents of an anxious child, as it is to work with the child because how the parents react to the child’s illness provides the basic model that the child will absorb how to react to the condition.

Alternatively, recent studies have shown that psychiatric symptoms may precede a first seizure (13,71). If this is the case, then mood symptoms may not be reactive to incurring epilepsy, but rather represent an alternative manifestation of an underlying CNS disorder that is capable of giving rise to both mood symptoms and epilepsy.