Diagnosis

Recognizing depression and making an accurate diagnosis is the first step toward developing a treatment plan. Depression can be a primary disorder; or it may be secondary to a medical condition, be substance induced, or occur in response to a specific stressor (eg, parental divorce, death of a family member, abuse). The latter is commonly labeled as an adjustment disorder and does not constitute a major psychiatric disorder, although it still can markedly impair a child’s ability to function and require interventions. Evidence suggests that depression seldom occurs by itself in children and adolescents. A young patient may display behaviors that warrant simultaneous diagnoses of affective, anxiety, or personality disorder, drug abuse, family conflicts, gender identity disorder, and others. Furthermore, depressive signs and symptoms are common features of many behavioral disturbances, such as “not being able to concentrate.” Identification and clarification of concurrent diagnoses may require repeated assessments over time. Such an effort is vital, because a comorbid diagnosis such as substance abuse or trauma can alter markedly both the course of the depression and the long-term prognosis of the patient.

At all ages, prominent features of the primary psychiatric depressive disorders include alterations in mood—either depression or irritability—with concomitant changes in sleep, interest in activities, feelings of guilt, loss of energy, impaired concentration, changes in appetite, psychomotor processing (retardation or agitation), and suicidal ideation. Compared with depressed prepubescent children, depressed adolescents may be more likely to experience anhedonia, defined as a profound lack of enjoyment in life and activities, hypersomnia, significant weight gain, and hopelessness. Co-occurrence of depression and substance abuse is common in teens. Often the substance use is noted as a likely cause of the depression; however, there is also significant data to suggest that depression in adolescence may be a predisposing factor for later substance abuse disorders, even in the absence of persistent mood disturbance. Psychosis, although rare, can occur as part of a depressive episode and may suggest a higher likelihood of developing bipolar illness at a later age.

One confusing aspect of depression in children and adolescents is that their symptoms may be less persistent and consistent over time than is the case for adults. Thus, parents not uncommonly will report that their child is sullen and irritable around the home yet seems happy and friendly with peers. Some incorrectly interpret this inconstancy of mood as proof that the child must not be “really” depressed. It is important to ask about mood states in a variety of circumstances, especially how the child feels when alone and not under specific demands, such as when doing homework or in the company of peers. Younger children, and even some teens, can be quite concrete in their thinking and may lack the vocabulary to describe feeling “depressed.” These children may think of the feeling as “sad,” “bored,” “down,” or “irritable.” Parents and teachers often may report that the child is not clearly depressed so much as irritable, short-fused, or angry; moreover, some children describe similar mood states rather than depression. Using several descriptors can help avoid missing a persistent impairment of mood. One acronym that captures criteria for major depression is SIGE-CAPS ( Box 1 ), with the requirement that 5 of 9 of these symptoms be present for at least 2 solid weeks “most days, most of the day” to meet diagnostic criteria.

Changes such as deteriorating school performance, a notable loss of friends, or a significant curtailment of previously enjoyable activities are relatively late indicators of major depression. Subtler, early signs may be decreased initiative in contacting friends and a withdrawal from family routines. Of course, such behaviors may also be well within the scope of normal behavior or indicative of other mental health disorders. Family history of depression can be a helpful clue, when present, but the inheritance patterns differ markedly among various subtypes of affective disorders.

A diagnosis of dysthymia requires fewer symptoms than major depression but of a longer duration. The requirement that symptoms be present for at least 1 year in children and teens with no period of more than 2 months symptom-free connotes a chronicity and pervasiveness that can have very serious consequences on the youth’s development. Though considered to be a “milder” form of depression, dysthymia has significant long-term costs to the development of the child. Furthermore, 70% of youth with dysthymia go on to have a major depressive episode.

Even if the specific diagnosis is unclear, it often may be best for clinicians to assume that the depressive symptoms are important, whether or not they are primary. Efforts to intervene with the depression may help clarify other problems, but clinicians should not conclude that depression necessarily is the only or even the most important reason a patient might have signs and symptoms of depression. Subclinical depression that does not meet full criteria for diagnosis still has significant negative impact on function, and early treatment may prevent the development of a full-blown major depressive episode and lessen impact on function and development.

One useful way of screening populations for mood disorders and suicide risk is to use structured measures, of which several are readily available. These measures typically are self-administered, take little time, and are easy to score. Moreover, they can be useful for initial screening and for monitoring treatment response. Some data suggest that children, or at least teens, may be more likely to endorse symptoms on a pen-and-paper questionnaire than in face-to-face direct inquiry. There are multiple screening tools that are valid and reliable for screening for adolescent depression available in the public domain. Several available tools include the K-SAD, PHQ 9 modified for adolescents, and the Columbia Depression Scale.

Treatment options

Once a clinician has diagnosed a depressive disorder in a child or adolescent, educating the patient and family about the disorder and treatment options is the first step toward planning an effective intervention. Deciding what level of care, for example, outpatient or inpatient, and what modality of treatment is indicated, for example, psychotherapy and/or pharmacotherapy, as well as developing a crisis plan are important components of this early assessment and intervention. It is important to determine what part of the care and management will be provided within the primary care setting.

Having these resources handy and up to date facilitates better care and alleviates provider stress related to acute situations when patients present with depression. If a provider or practice is committed to screening and treating depression in youth, knowing the resources is essential.

Typical treatment options for youth fall into 2 broad categories: pharmacologic and nonpharmacologic. Many published guidelines exist that can assist in decision making, which were developed in part in response to the concern raised when the “black-box” warning was issued by the Food and Drug Administration (FDA) in 2003. These guidelines include the practice parameters by the American Academy of Child and Adolescent Psychiatry (AACAP) and the updated Texas Children’s Medication Algorithm Project (CMAP). Both the United Kingdom and Canada have drafted similar documents with similar recommendations. Several variables often influence, if not dictate, the clinician’s decision about treatment, including the severity of symptoms and impact on function, duration of symptoms, family and patient preference, family history of medication responsiveness, and suicide risk. In less complicated, first episodes with mild or moderate symptoms and impairment, active monitoring may be indicated for 1 month. The availability and a patient’s willingness and capacity to access specific interventions or therapy may warrant a course of therapy before introducing medication. Practice guidelines that provide stepwise systematic approaches to treatment, often in a stage-of-treatment model, and some treatment algorithms are available to assist clinicians in making these choices. A recent article suggests that use of these algorithms improves outcome.

There is a growing body of evidence to assist the clinician in making decisions about rank ordering the interventions or sequencing them. One, a multisite study funded by the National Institute of Mental Health (NIMH) called the Treating Adolescent Depression Study (TADS), compared the use of a selective serotonin reuptake inhibitor (SSRI) alone, cognitive behavioral therapy (CBT) alone, or the two in combination. The findings indicated that the combination of CBT and fluoxetine offered the highest treatment response rates. Fluoxetine alone had significant response rates, whereas CBT alone did not.

A second NIMH-funded multisite study in progress, called Treatment of Resistant Depression in Adolescents (TORDIA), looked at the sequencing of treatments for individuals who do not respond to an initial SSRI trial. The comparison groups include a second SSRI, an antidepressant from a different class, or adding CBT. The advantage of these 2 studies is that they compare 2 active treatment arms rather than active treatment to placebo and are designed to more accurately mirror real-world patient populations and practices. There were no differences in the response rates for either medication switch; however, the addition of CBT led to greater response than medication switch alone.

The response rate for children and adolescents with major depressive disorder during the acute phase of treatment to a first antidepressant is 50% to 60%, and the response for those who fail a first trial is 40% to 50% when tried on a second agent. Because mood disorders tend to be recurring and relapsing conditions, even when a patient responds well to medication, several issues remain to be addressed. It is important to explore whether other adjunctive therapy is needed. Some patients do well once the depression has lifted and return readily to their activities. For others, the disruption to self-esteem and interference with other critical tasks of development are more profound and less easily dispelled. School performance may suffer, as may peer relationships. Especially in adolescents, for whom self-image is crystallizing, effects on self-confidence and self-esteem may be profound and enduring. Specific inquiry into such areas of function can help the patient and family identify additional services that may be of help in completing the return to full function.

Tailoring individual needs to available resources is a common challenge in designing a treatment program for depressed patients. Ongoing contact with the patient is vital for success. Helping the child or adolescent feel supported while fostering individual responsibility requires a delicate balance, especially early in treatment. Parents must be recruited as allies, even as their contributions in the environment in which their child is failing to thrive is acknowledged and altered. When chronic conflict within the family is a prominent part of the clinical picture, these dual perspectives sometimes are maintained best if patients and parents work with different individuals who can coordinate the treatment with each other.

In the case of depression, patients or families who do not want to use medications have clear, research-based options. Cognitive-based and other time-limited therapies have proven efficacy ; however, availability of these options varies markedly across the United States. Further, these types of interventions have focused almost exclusively on adolescents; their efficacy for younger patients remains unclear. Typical models include CBT and interpersonal therapy (IPT). Where family conflict seems to play a major contributing role, referral for family therapy should be considered. If an adolescent resists individual therapy, some adolescents may be more open to services delivered in a groups setting or that are school based.

Primary care providers generally will prescribe from 2 main categories of antidepressants: an SSRI and/or a serotonin-norepinephrine reuptake inhibitor (SNRI). The tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are rarely used, even by child psychiatrists, given their higher risk profile for adverse effects and toxicity, especially in overdose and lack of demonstrated efficacy. Both the ready availability of less toxic alternatives and research suggesting that TCAs are not effective in treating depression in adolescents have resulted in a significant decrease in their use. No TCAs are FDA endorsed for depression in children or teens. Some MAOIs are FDA endorsed for depression in youth older than 16 years, but they are rarely if ever used as a first-line choice.

The first relatively convincing evidence that an antidepressant can effectively treat depression in children and adolescents was published in 1997 and looked at fluoxetine, an SSRI. Evidence for such benefits has accrued only over the past few years, and these studies seem to confirm that, at least for some SSRIs, antidepressants can be safe and effective for treating depression in both children and adolescents. FDA-endorsed SSRIs for depression include fluoxetine for children 8 years and older and escitalopram in adolescents 12 years and older. Citalopram and sertraline, which have some, though mixed, support from randomized controlled trials (RCTs), are also reasonable alternatives despite lack of FDA endorsement.

Paroxetine, however, is relatively contraindicated, due to its short half-life and associated withdrawal symptoms and higher association with suicidal ideation during treatment. Fluoxetine has the benefit of a very long half-life, so mixed compliance is less likely to lead to subtherapeutic levels; it does, however, have significant cytochrome-P450 interactions, and is a potent inhibitor of the 2D6 enzyme thus having potential for significant D-D interactions. Citalopram and escitalopram have limited cytochrome-P450 effects so may be advantageous for youth on multiple other medications. Considering the cost of the specific medication is critical when this may preclude a family being able to afford the recommended treatment.

Because side effects can vary widely across patients, clinicians need to be prepared for the paradoxical or unexpected effects. Common side effects fall into several organ systems, predominantly central nervous system, gastrointestinal, and sexual. Central nervous system effects include agitation or restlessness, sleep (insomnia or sedation), headaches, tremor, and apathy. Gastrointestinal changes include changes in appetite, weight gain or loss, nausea, and occasionally diarrhea. Sexual effects that may be of particular importance to adolescents and yet difficult for them to discuss relate to sexual function. Most SSRIs have a notable incidence of anorgasmia that can affect both males and females. The effect is dose-related and reversible, but it is wise to mention this possibility even to adolescents who state that they are not sexually active. Many of these side effects also occur commonly as concomitants of depression, so patients should be urge to report any abrupt onset of such symptoms timed with starting or changing the dose of medication. Other postmarketing adverse events that may present to the pediatrician include epistaxis, purpura, enuresis, sinusitis, diaphoresis, and diastolic hypertension.

Although the SSRIs typically are well tolerated and previously were thought to require little or no monitoring for safety, recent controversy has raised significant concerns regarding their potential for inducing suicidal thoughts, behaviors, and violence. A review of 24 studies using SSRIs prescribed to teens looked at adverse event reporting, and noted a twofold increase—from 2% to 4%—reporting suicidal ideation or behaviors. Although there is a slight increase in the risk of suicidality among youth in the acute phase of treatment with an antidepressant, there is a lack of evidence to prove causality. This finding led to the addition in October 2004 of a black-box warning on all antidepressants prescribed to children or adolescents. Patient and family education must include warnings about possible new-onset suicidal ideation that may or may not be related to such adverse side effects as behavioral activation, akathesia, mania, or acute delirium. The FDA recommendations include weekly visits for the first month after initiating a trial of all antidepressants, followed by every other week for 2 more visits. Patients should be reevaluated again for response and adverse effects at least at 12 weeks and then as needed. Despite these recommendations, large-scale reviews of actual practice have indicated that fewer than 5% of youth experience this level of supervision; in fact, approximately 40% of children do not even have 3 visits in the 3 months following starting on an antidepressant. These warnings may have contributed to a decrease in prescribing from 2003 to 2005 with a concomitant increase in completed suicides.

Pediatricians who find the aforementioned information intimidating should be aware that studies that specifically measured suicidal thinking and behaviors before and during treatment actually showed no change or even a decrease in suicidal thinking and behaviors with use of SSRIs. In addition, in the TADS, suicidal ideation dropped from 29% to 10% with treatment, though suicide-related events were higher (7% vs 4%). Also, no completed suicides have occurred in more than 4000 pediatric subjects in trials with antidepressants (2200 with SSRIs), even with this being a potentially higher than average-risk population. Because it is commonly observed that energy and motivation may improve earlier in treatment than depressed mood leaving patients more vulnerable to act on previous suicidal thoughts, and that depression carries its own inherent risks, closer monitoring early in a trial of antidepressants is now recommended. A useful resource for practitioners and for parents can be found at medguide.org or parentmedguide.org , respectively.

Although suicide rates are fortunately much lower than rates of mood disorders, suicide remains the third leading cause of death in older adolescents and the fifth leading cause of death in children between 5 and 14 years of age. In general, completed suicides escalate rapidly during the adolescent years. Some studies suggest that as many as 25% of adolescents have seriously considered committing suicide, and perhaps 9% of adolescents attempt suicide at least once. Whereas males predominate in completed suicides, females are greatly overrepresented among those who survive a suicide attempt. Alarmingly, trends in the suicide method used by females has recently shifted to use of more lethal methods such as hanging, which were previously used more by males and may likely contribute to the observed increased death rates for females by suicide.

Because it is a true emergency and often offers the first access to a depressed child or adolescent, an active suicide attempt or threat of suicide demands a careful assessment. Although efforts are under way to standardize suicide assessment of youth, as yet no system has achieved widespread use. Common features among assessment tools suggest some key factors that clinicians can consider in evaluating the risk of a particular child or adolescent for completing a suicide, and are captured by the acronym “Sad Persons” ( Box 2 ).

Developmental influences can potentiate risk of suicide ideation and attempts, as children and teens may be more apt to react to “minor” stressors such as rejection by a peer, a poor grade, or teasing with self harm. Severe suicidal intent tends to be an acute problem that typically abates rapidly, if the individual receives the necessary support during the crisis, so accurate assessment and appropriate intervention literally can be lifesaving.

Knowledge about general strategies for evaluating and intervening with young, suicidal patients is necessary for all primary care providers. It is important for clinicians to identify both immediate factors leading up to the suicide attempt and acute or chronic mental disorders, including depression that might promote suicidality. Perhaps the most important intervention is to ask: asking if someone is suicidal does not make him or her more likely to commit suicide. Quite to the contrary, those who harbor such thoughts often are terrified to reveal such ideas spontaneously but will discuss the issue freely if invited to do so. If suicidal ideation is suspected, it is crucial to seek an explicit exploration of intention and access to possible suicidal means. A study of emergency room suicide evaluations indicated that most physicians fail even to ask if there are guns in the house. If suicidal intent seems high, hospitalization may well be needed; otherwise, the family needs to be recruited in a frank discussion of who will be with the child or adolescent and what steps can be taken to ensure safety. Serious suicidal intent is the most frequent justification for inpatient care for children or adolescents; the intent is both to protect the individual and to begin establishing contributing factors.

Essentially all antidepressants can induce mania in susceptible individuals; thus, awareness of the risk of bipolar illness is important when initiating a trial of antidepressants for depression. All patients and families should be advised of the possibility of a manic response, particularly those with a family history of bipolar illness. A medication-induced manic state does not automatically lead to a diagnosis of bipolar illness to the child, because some individuals will become manic only when on an antidepressant. More controversial is whether a drug-induced manic state has any long-term adverse consequences for young patients who are at risk for developing bipolar affective disorder. To date, no compelling evidence exists to suggest that an antidepressant trial should be avoided even when a strong suspicion of a bipolar affective disorder exists; however, emergence of manic symptoms after initiation of an antidepressant, usually between the first and fourth weeks, should result in prompt cessation of the medication and diagnostic and clinical reassessment. Early indicators of this switch to mania may include elated mood, decreased need for sleep, grandiosity, hypersexuality, racing thoughts, and pressured speech.

Another concern when prescribing SSRIs is the serotonin syndrome, which can occur when a patient is on high doses of an SSRI or is taking several medications that, together, increase total brain serotonin concentrations. Though relatively rare, this potentially lethal syndrome often resembles flu-like symptoms or sepsis, with fever, disorientation, confusion, agitation, tremor, muscle twitching and myoclonus, excess salivation, and ataxia; its presence constitutes a medical emergency. There have been no reports of long-term adverse effects from SSRIs, and “routine” monitoring of major organ functioning is not required. However, because many are metabolized through the cytochrome P450 enzyme system, interactions with other medications must be considered.

Discontinuation syndrome, especially relevant with SSRIs with shorter half-lives, such as paroxetine and fluvoxamine, also can be important. In general, a slow taper of several weeks is appropriate and minimizes likelihood of problems, regardless of the SSRI being used.

Because SSRIs are generally the first-line pharmaceutical agent for treating depression in youth at this time and a patient may respond to a different drug in the same class, a reasonable standard of practice for physicians caring for children and adolescents is to develop familiarity with at least 2 or 3 of the SSRIs. In the absence of marked side effects, an adequate trial typically would be 8 to 10 weeks at a usual therapeutic dose for that medication. After a failure of 2 SSRIs, most treatment guidelines recommend switching to a non-SSRI. Often this is the point at which many primary care physicians will seek a consultation from a child and adolescent psychiatrist. Of course, sudden deterioration, suicidal ideation, psychotic ideation, comorbid substance abuse, or unusual responses to or side effects from treatment interventions also suggest the need for such a consultation.

Newer antidepressants that are not SSRIs such as bupropion, venlafaxine, desvenlafaxine, mirtazapine, and duloxetine are less well studied in young patients but may offer additional treatment options. It must be emphasized that the research base remains small, especially in terms of possible long-term consequences of using antidepressants of any type for this age range. Nevertheless, some of the newer agents may be particularly useful when certain comorbidities are present, for example, prescribing bupropion when patients also have attention-deficit/hyperactivity disorder (ADHD) or venlafaxine when anxiety also is present. Venlafaxine has been studied in 3 RCTs that did not show efficacy in nontreatment-resistant pediatric patients; however, venlafaxine was effective in the TORDIA study for treatment-resistant teens ; pooled analysis of 2 identical studies did show effectiveness for teens but not for children. Mirtazapine is a serotonin receptor-2 antagonist. Two pediatric RCTs have been conducted, neither of which showed superiority over placebo. In a single, open-label trial with bupropion, adolescents with and without ADHD had reduced depressive symptoms after 2 weeks. Duloxetine is a relatively newly available SNRI for which no RCT with minors exists. Box 3 provides a summary of available antidepressant medications and the recommended dosing strategies.

Box 3

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