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Fast Facts

A brief refresher with useful tables, figures, and research summaries

Mood Disorders

The diagnosis of a primary mood disorder is clinical, based on history and examination. This section covers the following:

Diagnostic Criteria
Evaluation and Management of Mood Disorders
Safety and Suicidality
Prognosis

Diagnostic Criteria

Major Depressive Disorder

Depression is characterized by episodes of sustained low or irritable mood and impairment of function. The cumulative incidence of depression by age 18 years in community samples is estimated at 20%; results from the 2018-2019 National Survey on Drug Use and Health indicated that 20.9% of adolescents ages 12-17 years had ever experienced a major depressive episode. Depression in children can present differently than in adults; children and adolescents may not report or exhibit traditional depressive symptoms (e.g., sad, empty, or irritable mood), but rather symptoms may include irritability, mood lability, low frustration tolerance, temper tantrums, somatic complaints, and social withdrawal.

[Image] — **Prevalence and Demographics of Depression**

Summary of DSM-5-TR Diagnostic Criteria for Major Depressive Disorder
A major depressive episode is defined as the presence of A, B, and C: Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure: depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful); note: in children and adolescents, can be irritable mood markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation) significant weight loss when not dieting, or weight gain (e.g., a change of more than 5% of body weight in a month) or decrease or increase in appetite nearly every day; note: in children, consider failure to make expected weight gain insomnia or hypersomnia nearly every day psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) fatigue or loss of energy nearly every day feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a specific suicide plan, or a suicide attempt The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The episode is not attributable to the physiological effects of a substance or another medical condition. At least one major depressive episode is not better explained by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders. There has never been a manic episode or a hypomanic episode, except if all manic/hypomanic episodes are substance-induced, due to the physiological effects of another medical condition, or both.

Summary of DSM-5-TR Diagnostic Criteria for Major Depressive Disorder

A major depressive episode is defined as the presence of A, B, and C:

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure:
- depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful); note: in children and adolescents, can be irritable mood
- markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation)
- significant weight loss when not dieting, or weight gain (e.g., a change of more than 5% of body weight in a month) or decrease or increase in appetite nearly every day; note: in children, consider failure to make expected weight gain
- insomnia or hypersomnia nearly every day
- psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
- fatigue or loss of energy nearly every day
- feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
- diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
- recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a specific suicide plan, or a suicide attempt
The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
The episode is not attributable to the physiological effects of a substance or another medical condition.
At least one major depressive episode is not better explained by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.
There has never been a manic episode or a hypomanic episode, except if all manic/hypomanic episodes are substance-induced, due to the physiological effects of another medical condition, or both.

Bipolar Disorder

Bipolar disorder is commonly identified in late adolescence or adulthood, but it can occur in younger children. The estimated combined prevalence of bipolar I and II disorders in children and adolescents is 2.6%, but the rate increases to 6% when subthreshold and spectrum cases are included.

Bipolar disorder often includes depressive episodes and periods of elevation (mania or, in bipolar II, hypomania) that can be severe enough to warrant hospitalization. Both bipolar I and II disorders should be marked by clear, distinct change in mood and function, typically with elevated mood, irritability, or both, as well as associated symptoms that include increased talkativeness, decreased need for sleep, increased energy, impulsiveness, grandiosity, and psychosis. In bipolar II, the diagnosis includes criteria for a major depressive episode.

Other common pediatric conditions are associated with symptoms similar to hypomania or mania but do not reflect bipolar disorder. For example:

Irritability is a common manifestation of a number of mental health disorders in children. Disruptive mood dysregulation disorder (DMDD) is a newly classified disorder meant to distinguish bipolar disorder in youth from bipolar disorder in adults, especially when persistent irritability with dysregulation is the primary presenting symptom.
Distractibility, increased talkativeness, and impulsiveness are common hallmarks of attention deficit-hyperactivity disorder (ADHD), which can also be associated with sleep disturbances and increased energy. However, these symptoms are persistent in ADHD rather than marked by distinct onset in manic or hypomanic episodes. Although bipolar disorder and ADHD can co-occur, bipolar episodes of (hypo)mania mark distinct elevation of existing symptoms or new symptoms (e.g., grandiosity or psychosis) that are not consistent with ADHD.

Identifying hypomanic or manic episodes is not based solely on a comparison to the patient’s baseline mood. Depressed patients may compare periods of euthymia (normal mood) to depressive episodes and describe their mood as happier than normal, needing less sleep, having more energy, engaging in more activities. Further, children will often use their most recent experiences as their point of comparison. Therefore, it is important to clarify if episodes of potential (hypo)manic symptoms reflect aberrations of typical behavior for individuals of the same developmental stage.

Summary of DSM-5-TR Diagnostic Criteria for Bipolar I Disorder
For a diagnosis of bipolar I disorder, it is necessary to meet criteria for a manic episode. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and persistently increased energy or activity lasting at least one week (or any duration if hospitalization is required). During this time, three (four if mood is only irritable) or more symptoms must be present and represent a change from baseline: inflated self-esteem or grandiosity decreased need for sleep more-talkative or pressured speech (difficult to interrupt) racing thought or flight of ideas distractibility increased goal-directed activity or psychomotor agitation excessive involvement in activities that have high potential for painful consequences Note: Disturbance of functioning must be a change from baseline and notable to others.

Summary of DSM-5-TR Diagnostic Criteria for Bipolar I Disorder

For a diagnosis of bipolar I disorder, it is necessary to meet criteria for a manic episode. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and persistently increased energy or activity lasting at least one week (or any duration if hospitalization is required). During this time, three (four if mood is only irritable) or more symptoms must be present and represent a change from baseline:

inflated self-esteem or grandiosity
decreased need for sleep
more-talkative or pressured speech (difficult to interrupt)
racing thought or flight of ideas
distractibility
increased goal-directed activity or psychomotor agitation
excessive involvement in activities that have high potential for painful consequences

Note: Disturbance of functioning must be a change from baseline and notable to others.

Summary of DSM-5-TR Diagnostic Criteria for Bipolar II Disorder
For a diagnosis of bipolar II disorder, criteria must be met for a hypomanic and major depressive episode (see criteria for MDD above). A hypomanic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and persistently increased energy or activity lasting at least 4 days. During this time, three (four if mood is only irritable) or more symptoms must be present and represent a change from baseline: inflated self-esteem or grandiosity decreased need for sleep more-talkative or pressured speech (difficult to interrupt) racing thought or flight of ideas distractibility increased goal-directed activity or psychomotor agitation excessive involvement in activities that have high potential for painful consequences Note: Disturbance of functioning must be a change from baseline and notable to others but not so severe as to require hospitalization or result in psychosis (when it would constitute mania and bipolar I disorder). Furthermore, the symptoms cannot be due to substances, medical conditions, or other psychiatric conditions.

Summary of DSM-5-TR Diagnostic Criteria for Bipolar II Disorder

For a diagnosis of bipolar II disorder, criteria must be met for a hypomanic and major depressive episode (see criteria for MDD above). A hypomanic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and persistently increased energy or activity lasting at least 4 days. During this time, three (four if mood is only irritable) or more symptoms must be present and represent a change from baseline:

inflated self-esteem or grandiosity
decreased need for sleep
more-talkative or pressured speech (difficult to interrupt)
racing thought or flight of ideas
distractibility
increased goal-directed activity or psychomotor agitation
excessive involvement in activities that have high potential for painful consequences

Note: Disturbance of functioning must be a change from baseline and notable to others but not so severe as to require hospitalization or result in psychosis (when it would constitute mania and bipolar I disorder). Furthermore, the symptoms cannot be due to substances, medical conditions, or other psychiatric conditions.

Disruptive Mood Dysregulation Disorder (DMDD)

DMDD was added to the DSM-5-TR to provide developmentally appropriate diagnostic criteria for severe irritability in children and adolescents. DMDD is characterized by constant, debilitating irritability in children and teens that does not fit existing diagnostic categories for bipolar or depressive disorders. This irritability and associated outbursts must be out of proportion to typical behavior for the child’s age and development, and not better explained by another diagnosis.

For example, in a patient with intellectual disability or autism spectrum disorder who requires substantial support, a diagnosis of DMDD would only apply if the patient’s irritability and dysregulation is not considered typical for the child’s functional developmental level based on the neurodevelopmental conditions.

Irritability and behavioral dysregulation can arise in a number of other psychiatric conditions in pediatric patients, including posttraumatic stress disorder (PTSD), reactive attachment disorder, and depression. The presence of these disorders does not preclude a diagnosis of DMDD, but the nature and onset of irritability and associated symptoms must be clearly distinct from symptoms associated with the other diagnoses.

For example, a patient with comorbid DMDD and MDD would experience irritability that is persistent and without features of MDD, as well as clear episodes of low mood and neurovegetative symptoms consistent with depressive episodes.

A diagnosis of DMDD does not replace the diagnosis of bipolar disorder in pediatric populations but rather reflects a distinct mood disorder. It also does not preclude the development or diagnosis of bipolar disorder if a hypomanic or manic episode arises. Thus, bipolar disorder can still be diagnosed in pediatric populations, but it requires clear, distinct episodes of mania or hypomania (often with euphoria or distinct mood changes) separate from baseline severe, nonepisodic irritability. Furthermore, once an episode of mania or hypomania occurs, or a diagnosis of bipolar disorder is made, a diagnosis of DMDD is no longer appropriate for that patient.

Because MDD and DMDD can manifest with irritability, distinguishing them can be difficult. A primary means to separate these two disorders when irritability is the primary mood disorder is to identify the periodicity of the irritability; if the irritability is episodic, rather than persistent, then a diagnosis of MDD should be considered.

Summary of DSM-5-TR Diagnostic Criteria for Disruptive Mood Dysregulation Disorder
The diagnosis of DMDD cannot be made before age 6 or after 18 years of age. The following symptoms must be present on history or by observation before age 10, occur for 12 or more months with no period lasting 3 or more consecutive months without any symptoms, and must occur in two or more settings: Severe recurrent temper outbursts are manifested verbally (e.g., verbal rages) and/or behaviorally (e.g., physical aggression toward people or property) and are grossly out of proportion in intensity or duration to the situation or provocation. The temper outbursts are inconsistent with developmental level. The temper outbursts occur, on average, three or more times per week. The mood between temper outbursts is persistently irritable or angry most of the day, nearly every day, and is observable by others (e.g., parents, teachers, peers). There has never been a distinct period lasting more than one day during which the full symptom criteria, except duration, for a manic or hypomanic episode have been met. The behaviors do not occur exclusively during an episode of major depressive disorder and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive disorder). This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major depressive disorder, attention deficit-hyperactivity disorder, conduct disorder, and substance use disorders. Individuals whose symptoms meet criteria for both DMDD and either oppositional defiant disorder or intermittent explosive disorder should only be given the diagnosis of DMDD. If an individual has ever experienced a manic or hypomanic episode, the diagnosis of DMDD should not be assigned. The symptoms are not attributable to the physiological effects of a substance or another medical or neurologic condition.

Summary of DSM-5-TR Diagnostic Criteria for Disruptive Mood Dysregulation Disorder

The diagnosis of DMDD cannot be made before age 6 or after 18 years of age.

The following symptoms must be present on history or by observation before age 10, occur for 12 or more months with no period lasting 3 or more consecutive months without any symptoms, and must occur in two or more settings:
- Severe recurrent temper outbursts are manifested verbally (e.g., verbal rages) and/or behaviorally (e.g., physical aggression toward people or property) and are grossly out of proportion in intensity or duration to the situation or provocation.
- The temper outbursts are inconsistent with developmental level.
- The temper outbursts occur, on average, three or more times per week.
- The mood between temper outbursts is persistently irritable or angry most of the day, nearly every day, and is observable by others (e.g., parents, teachers, peers).
There has never been a distinct period lasting more than one day during which the full symptom criteria, except duration, for a manic or hypomanic episode have been met.
The behaviors do not occur exclusively during an episode of major depressive disorder and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive disorder).
This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major depressive disorder, attention deficit-hyperactivity disorder, conduct disorder, and substance use disorders. Individuals whose symptoms meet criteria for both DMDD and either oppositional defiant disorder or intermittent explosive disorder should only be given the diagnosis of DMDD. If an individual has ever experienced a manic or hypomanic episode, the diagnosis of DMDD should not be assigned.
The symptoms are not attributable to the physiological effects of a substance or another medical or neurologic condition.

Premenstrual Dysphoric Disorder

Premenstrual dysphoric disorder is characterized by marked mood lability, irritability, dysphoria, and anxiety that occur cyclically in association with the premenstrual phase of menses for the majority of cycles over the course of a year. Symptoms must result in functional impact, and anxiety or mood symptoms must be present. Symptoms typically resolve with onset of menses but can persist into menses. However, a clear period of minimal or no symptoms during the post-menses week is required.

DSM-5-TR Diagnostic Criteria for Premenstrual Dysphoric Disorder
In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses. One (or more) of the following symptoms must be present: marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection) marked irritability or anger or increased interpersonal conflicts marked depressed mood, feelings of hopelessness, or self-deprecating thoughts marked anxiety, tension, and/or feelings of being keyed up or on edge One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from criterion B above. decreased interest in usual activities (e.g., work, school, friends, hobbies) subjective difficulty in concentration lethargy, easy fatigability, or marked lack of energy marked change in appetite; overeating; or specific food cravings hypersomnia or insomnia a sense of being overwhelmed or out of control physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain The symptoms in criteria A-C must have been met for most menstrual cycles that occurred in the preceding year. The symptoms cause clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home). The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder, or a personality disorder (although it may co-occur with any of these disorders). Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.) The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

DSM-5-TR Diagnostic Criteria for Premenstrual Dysphoric Disorder

In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses.
One (or more) of the following symptoms must be present:
- marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection)
- marked irritability or anger or increased interpersonal conflicts
- marked depressed mood, feelings of hopelessness, or self-deprecating thoughts
- marked anxiety, tension, and/or feelings of being keyed up or on edge
One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from criterion B above.
- decreased interest in usual activities (e.g., work, school, friends, hobbies)
- subjective difficulty in concentration
- lethargy, easy fatigability, or marked lack of energy
- marked change in appetite; overeating; or specific food cravings
- hypersomnia or insomnia
- a sense of being overwhelmed or out of control
- physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain
The symptoms in criteria A-C must have been met for most menstrual cycles that occurred in the preceding year.
The symptoms cause clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).
The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder, or a personality disorder (although it may co-occur with any of these disorders).
Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.)
The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

Evaluation and Management of Mood Disorders

Evaluation

Etiology and risk factors: Major depressive disorder is a familial disorder related to the interaction of genetic and environmental factors. A family history of the disorder is the most predictive risk factor. Successful treatment of mothers with depression is associated with significantly fewer new psychiatric diagnoses and higher remission rates of existing disorders in their children. Additionally, some evidence indicates that anxiety disorders in children are a precursor for depression. Approximately 20% of children with putative depression will experience a manic episode by adulthood, establishing a diagnosis of bipolar disorder.

Bipolar disorder also has a strong genetic component. First-degree relatives of affected individuals have a four- to sixfold increased risk of developing bipolar disorder. Premorbid difficulties are common with bipolar disorder, including disruptive behaviors, irritability, and behavioral dysregulation.

Screening: Clinicians should screen all children and adolescents for key depressive symptoms, including depressed or sad mood, irritability, and anhedonia. If symptoms are present, a more thorough evaluation should be undertaken by asking about DSM-5-TR criteria noted above or by utilizing a rating scale. The Patient Health Questionnaire-9 (PHQ-9) is a nine-point rating scale validated for use as a screen for depression in patients aged 12 and older; the PHQ-2 includes the first two questions on the PHQ-9 and is sometimes used as a first-pass screening tool.

Differential diagnosis: The differential diagnosis for mood disorders is broad. Comorbidities are common and important to consider, as are conditions that could be mistaken for a primary mood disorder, including the following:

Medical disorders may masquerade as mood disorders. Patients with thyroid abnormalities, mononucleosis, anemia, cancer, autoimmune diseases, and chronic fatigue syndrome can present with depressive symptoms. These conditions should be considered when evaluating a patient for new mood complaints, when patients do not improve, or when signs and symptoms of these other conditions exist.
Medications (e.g., glucocorticoids, contraceptives, and stimulants) can cause adverse effects that mimic symptoms of mood disorders.
Substance use can induce mood symptoms or a mood disorder. The presentation of acute intoxication can be similar to that of a depressive or manic episode. However, mania induced by a selective serotonin-reuptake inhibitor (SSRI) is considered to represent bipolar disorder rather than a substance-induced mood disorder.
Bereavement or acute loss or trauma can be associated with acute mood-related symptoms that can represent temporary symptoms or an adjustment disorder or can progress to a full mood disorder.
Anxiety and mood disorders are common comorbid conditions. Anxiety can precede mood disorders.
Other comorbidities include attention deficit-hyperactivity disorder, oppositional defiant disorder, and premenstrual dysphoric disorder.

Management

Nonpharmacologic Management: A key first step in management of mood disorders is to have patients engage in basic mood hygiene, which can include good nutrition, moderate exercise, healthy sleep habits, and maintaining a routine schedule. All clinicians can provide education regarding the benefits of treatment, which can reduce stigma and promote engagement in care.

Depression: Both cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) have been shown to be effective for treatment of depression as compared to placebo, although treatment effectiveness can be reduced by the presence of comorbid anxiety (especially with IPT), hopelessness, family conflicts, significant cognitive distortions, low global functioning, and suicidality.
- CBT for treatment of depression has been shown to be effective in adolescents, with a focus on psychoeducation and identification of negative cognitions (by challenging them with evidence and reframing them in a more realistic manner).
- IPT is another therapy modality indicated for depression, with a focus on reducing depressive symptoms while improving functioning through problem-solving and improved communication.
- Psychotherapy and antidepressant medications for treatment of depression have been associated with high rates of response. However, results of some randomized, controlled trials have shown high rates of response to both placebo and treatment. Patients with mild-to-moderate depression may respond well to therapy alone; more-severe cases will generally require augmentation with antidepressants.
  - The Treatment for Adolescents with Depression Study (TADS) demonstrated that a combination of CBT and SSRI treatment was superior to either treatment alone and was associated with more-rapid improvement in depression scores (particularly vs. psychotherapy alone) and greater protection against suicidality (vs. medication management alone).
Bipolar disorder: Psychotherapy for treatment of bipolar disorder is primarily utilized in the depressive stage, or for maintenance between episodes, due to the limited ability for patients to engage in therapy during manic episodes.
DMDD: Research on nonpharmacologic therapies for treatment of DMDD is still developing. IPT, CBT, and dialectic behavioral therapy for children (DBT-C) have been shown to have some benefit in children with a diagnosis of DMDD. Parental behavioral training has also been reported as beneficial. Currently, psychotherapy is the initial recommendation for treatment of DMDD, with pharmacologic interventions utilized for management of symptoms associated with the diagnosis as well as management of comorbid symptoms.
PMDD: While often requiring pharmacologic management, some evidence suggests that nonpharmacologic interventions including CBT, diet, exercise, and acupuncture may be beneficial for treatment of PMDD.

Pharmacologic Management

Antidepressants

Selective serotonin-reuptake inhibitors (SSRIs) are the mainstay of pharmacologic treatment for depressive illness. Depressed patients treated with SSRIs have a relatively good response rate (40%-70%), but the placebo response rate is also high (30%-60%), resulting in a number needed to treat (NNT) of 10 (i.e., 10 patients need to be treated for 1 patient to benefit). Adverse effects of SSRIs are generally benign and include gastrointestinal symptoms, sleep changes, restlessness, diaphoresis, headaches, akathisia, changes in appetite, and sexual dysfunction. Some studies suggest an increase in suicidal ideation and attempts (but not completed suicides) in children on SSRIs, resulting in the FDA black box warning to this effect. However, more than 10 times the number of depressed patients respond favorably to antidepressants than spontaneously report suicidality. Studies have also shown a correlation between the use of SSRIs and a decline in adolescent suicide. Although patients prescribed SSRIs should be screened regularly regarding suicidality at follow-up visits, current evidence does not support withholding medication treatment.
- Some data support the use of selective norepinephrine-reuptake inhibitors (SNRIs) in adolescents with treatment-resistant depression.
- SSRIs may be beneficial for some patients with DMDD.
- SSRIs, combined estrogen-progestin oral contraceptives, or both have shown some benefit for treatment of PMDD. In cases where SSRIs and oral contraceptives are insufficient, and symptoms are severe, gonadotropin-releasing hormone agonist therapy with estrogen and progesterone supplementation can be considered for symptom relief in consultation with specialists prior to initiation.
Other antidepressants, such as mirtazapine and tricyclic antidepressants (TCAs), have not been shown to be effective in child and adolescent depression, although data are limited. Antidepressants in patients with bipolar disorder may precipitate a manic switch or destabilize mood. However, antidepressants are sometimes carefully used to target depressive symptoms in patients with bipolar disorder who are already mood stabilized; this would typically only be attempted by (or in close consultation with) a psychiatrist.

Mood Stabilizers: Anticonvulsants and antipsychotics are the mainstay of treatment for bipolar disorder. However, evidence of their efficacy for bipolar disorder in the pediatric population is limited. Standard therapy is often extrapolated from adults and may include lithium, valproate, other anticonvulsant medications, and atypical antipsychotics. Information on individual patient circumstances, presenting symptoms, medical history, and family history can help in the selection of an agent.

Antipsychotics (including aripiprazole, risperidone, olanzapine, lurasidone, and quetiapine) are commonly used in the treatment of pediatric bipolar disorder. Although these agents can be quite effective, they can cause significant adverse effects, including metabolic derangements (e.g., increased weight, altered lipid profile) and less often, movement-related adverse effects (extrapyramidal symptoms).
Anticonvulsants are not as well studied in the pediatric population. Evidence is limited for the utility of lithium and valproate in pediatric bipolar disorder. Both lithium and valproate require regular monitoring of serum levels and are associated with significant long-term adverse effects. Lamotrigine is a well-tolerated mood stabilizer that requires slow titration to achieve therapeutic dosing but is less effective than other mood stabilizers in the treatment of mania.

Safety and Suicidality

Clinicians should screen for suicidal and homicidal ideation in all children and adolescents with mood disorders. Studies have shown that, when asked directly, adolescents are often open and honest about suicidality. If patients endorse thoughts about harming themselves, distinctions should be made between self-injurious urges without intent to die (e.g., cutting and other behaviors used to relieve strong negative feelings) and suicidal ideation or actions intended to end life. Because firearms are the most deadly method of successful suicide, patients should be screened for access to firearms and counseled about safe storage or removal.

Prognosis

A depressive episode can last several months. Although most youth will recover from their first depressive episode, recurrence rates are high, and a substantial proportion of children and adolescents with major depressive disorder will continue to suffer with depression in adulthood.

Bipolar disorder typically is a lifelong illness. Untreated bipolar disorder can be associated with significant social impairment and increased risk for catatonia and suicide. Effective and early engagement in treatment can reduce the risk of more-significant negative outcomes.

Premenstrual dysphoric disorder can occur any time after menarche but often is manageable with treatment. Symptoms cease after menopause.

When to refer:

diagnostic uncertainty
concern for bipolar disorder or psychosis
failed SSRI trials
safety concerns
history of psychiatric hospitalizations
comorbidity that increases complexity of management

Research

Landmark clinical trials and other important studies

Research

National Trends in Mental Health Care for US Adolescents

Mojtabai R and Olfson M. JAMA Psychiatry 2020.

Survey data between 2005 and 2018 indicated that mental health care for internalizing problems among adolescents increased whereas care for externalizing and relationship problems decreased.

Read the NEJM Journal Watch Summary

Variation in the 12-Month Treatment Trajectories of Children and Adolescents After a Diagnosis of Depression

Joyce NR et al. JAMA Pediatrics 2018.

Private insurance claims data indicated that psychotherapy monotherapy was the most common treatment for youths with a diagnosis of depression and most youths did not receive antidepressants. Overall, 13% of youths received no treatment, and 18% received antidepressants without concomitant psychotherapy.

Receipt of Evidence-Based Pharmacotherapy and Psychotherapy Among Children and Adolescents with New Diagnoses of Depression

Soria-Saucedo R et al. Psychiatr Serv 2016.

Based on private insurance data, 58% of depressed youths received at least one type of depression treatment, 33% received psychotherapy alone, 25% received medication alone, and 3% received combination treatment.

Usual Care for Adolescent Depression from Symptom Identification Through Treatment Initiation

O’Connor BC et al. JAMA Pediatrics 2016.

Most adolescents with newly identified depression symptoms received some treatment, usually including psychotherapy, within the first 3 months after identification. However, rates of follow-up care were low.

A Randomized Controlled Trial of Risperidone, Lithium, or Divalproex Sodium for Initial Treatment of Bipolar I Disorder, Manic or Mixed Phase, in Children and Adolescents

Geller B et al. Arch Gen Psychiatry 2012.

Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but was associated with more metabolic effects.

Antidepressant Exposure as a Predictor of Clinical Outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) Study

Sakolsky DJ et al. J Clin Psychopharmacol 2011.

In the TORDIA study, continued treatment for depression among treatment-resistant adolescents resulted in remission in approximately one-third of patients, a rate that is similar to the rate in adults. Eventual remission is evident within the first 6 weeks in many patients, suggesting that earlier intervention among nonresponders could be important.

The Treatment for Adolescents with Depression Study (TADS): Long-Term Effectiveness and Safety Outcomes

March JS et al. Arch Gen Psychiatry 2007.

This study demonstrated that a combination of CBT and SSRI treatment was associated with superior improvement in depression score and greatest protection against suicidality.

Read the NEJM Journal Watch Summary