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Abstract

Affective disorders in children and adolescents generally have a severe course of the illness, higher suicidal behavior, and adverse effect on overall development and life course. Presentation of pediatric depression and bipolar is usually different from adults, leading to longer delays in help-seeking and effective management. This narrative review highlights the magnitude, clinical presentation, comorbidity, differential diagnosis, and management approach of depression and bipolar in children and adolescents. Better awareness and expertise are essential for timely identification, comprehensive assessment, and holistic treatment.

Keywords

Depression bipolar affective disorder children adolescents

Mood disorders in children and adolescents significantly affect their development and life course. Recently, the recognition of depression and bipolar diagnoses has increased in the young population. Symptoms of mood disorders are present with different frequencies in children and adolescents, with a greater rate of comorbid psychiatric conditions than in adults. Early onset of depression and bipolar disorder (BD) have difficult course of the illness, a less favorable prognosis, and a higher suicidal rate. They frequently have a longer delay in presentation to diagnosis and management.

Epidemiology

Prevalence of major depressive disorder (MDD) is 2% in children and 4% to 8% in adolescents, with being similar in both the gender in children (male/female 1:1) and more females in adolescents (male/female 1:2–3). Depression is reported 3 times more commonly in children with a family history of mood disorder. The prevalence of persistent mood disorder is 0.6% to 4.6% in children and 1.6% to 8% in adolescents. The prevalence of disruptive mood dysregulation disorder (DMDD) is up to 3%, with being more common in males.¹

The prevalence of BD I and II is 2.5%, and of subthreshold symptoms is 5.7%. Contrary to the common notion, the number of children with BD has probably not increased.²

Nosology

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) has a few different clauses for mood disorders in children, but most criteria and symptoms are similar for adults. Following are the salient diagnostic features as described in DSM-5.³

Depression

As per DSM-5, MDD is diagnosed upon having a depressed or irritable mood or loss of interest or pleasure for at least 2 weeks, along with significant distress and functional impairment and at least 4 of the following symptoms—weight loss or lack of expected weight gain, or increased or decreased appetite; reduced or increased sleep; loss of energy or fatigue; poor concentration or decision making; psychomotor agitation or retardation; worthlessness or inappropriate guilt; death wish, suicidal behavior.³

Other diagnostic categories are persistent depressive disorder (chronically depressed or irritable mood for at least one year), DMDD, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, etc.

Manic Episode

As per DSM-5, Mania is diagnosed if the abnormally persistent elevated, or irritable mood and abnormally increased energy or goal-directed activity are present for at least one week (or lesser duration if hospitalization is necessary) along with 3 (or more) of the following symptoms (4 if the mood is only irritable): increased self-esteem; decreased need for sleep; over talkativeness; racing thoughts; distractibility; psychomotor agitation; excess involvement in potentially hazardous activities. It also causes marked impairment in functioning and is not attributable to the effect of medical conditions or substances.

Hypomanic Episode

As per DSM-5, hypomania is diagnosed with most of the criteria mentioned above but with a lesser duration of symptoms (at least 4 consecutive days) and a lack of functional disturbances.

Children are generally happy and goofy in the specific context. But these features persist beyond the developmental phase and appear inappropriate. In that case, it raises concern for further exploration of mood changes and other associated symptoms for appropriate diagnosis and timely management.³

The Presentation Across Ages and Types

Depression

In 1946, Spitz and Wolf observed infants upon separation from their parents and reported depressive symptoms in form of apprehensive facial expression, crying, screaming, apathy, reduced babbling and physical activity, withdrawal, and detachment from the environment. It was termed as “anaclitic depression.”⁴

Frommer subtyped childhood depression into 3 types—the enuretic group as immature, moody, hostile, and aggressive; the phobic depressive group as irritable, tense, and weepy; and the pure depressive group as irritable, with temper outbursts, sleep disturbances, and antisocial behavior.⁵

Clinical presentation of childhood depression varies across the developmental stages as young children behave differently than adolescents. Children with depression commonly have decreased social play, separation anxiety, irritability, tantrums, frustration, apathy, disinterest, withdrawal, reduced socialization, uncooperative behavior, somatic complaints, etc. In contrast, the presentation of depression in adolescents is almost similar to adults.⁶

Bipolar Disorder

The common symptoms are irritability, mood lability, distractibility, increased energy, and goal-directed activity (present in 75% of cases), though grandiosity and hypersexuality are more specific symptoms of bipolar.⁷

The systematic review by Ryles et al reported the following key feature and most prominent symptoms of BD in different age groups: in childhood-onset BD—irritability/aggression; in adolescent-onset BD—activity/energy, elation/euphoria; and in adult-onset BD—the pressure of speech/racing thoughts, grandiosity/bizarre thought content.⁸

A systematic review of BD in Asia by Subramanian et al reported a greater risk of developing BD in adolescents with attention deficit hyperactivity disorder (ADHD) with conduct disorder or oppositional defiant disorder. ADHD comorbidity leads to an earlier onset of mood episodes, with an increased risk of developing comorbid anxiety and substance use disorders.⁹

Concerns and Comorbidity

It is important to have a thorough assessment and consider the differential diagnosis of BD, as antidepressants can precipitate switch or activation in children or adolescents with undiagnosed BD. The following symptoms increase the risk of the switch-psychotic symptoms, marked psychomotor retardation, reverse neurovegetative signs (increased sleep and appetite), mood reactivity, and a family history of BD. Hence children and adolescents should be evaluated meticulously to prevent such risks.¹⁰

The following conditions are commonly present with childhood depression: anxiety disorders, substance use disorder, conduct disorder, oppositional defiant disorder, ADHD, and dissociative/conversion disorder.¹⁰

Childhood BD commonly presents with the following comorbid conditions: ADHD (most common comorbidity) (11%–90%), oppositional defiant disorder (46%–75%), conduct disorder (5%–37%), anxiety disorder (12%–77%), substance use disorder (~40%).¹¹

Differential Diagnosis

Common differentials for childhood depression are the following: ADHD, oppositional defiant disorder, DMDD, grief, post-traumatic stress disorder, generalized anxiety disorder, other anxiety disorders, medical conditions (anemia, thyroid, neurological disease, etc), medication-related depressive symptoms (steroid, oral contraceptive pills, antibiotics), substance-related depressive symptoms.¹

Common differentials for childhood bipolar are the following: ADHD, oppositional defiant disorder, DMDD, agitated anxious depression, mixed episode, substance abuse-related presentation, first-episode schizophrenia, depression with psychotic features, borderline personality traits or disorder.²

BD and ADHD have common features such as inattention, impulsivity, restlessness, and sensation seeking. In contrast, BD typically has discrete episodes, grandiosity, reduced need for sleep, hypersexuality, prominent mood symptoms, and rare onset in childhood, and ADHD commonly have nondiscrete, chronic symptoms, with typical onset in childhood.¹²

Classically BD shows a different trajectory than ADHD, as an anxiety disorder in childhood, and depressive and adjustment disorders in adolescence present as BD in early adulthood, while ADHD in childhood generally progresses to mood dysregulation and depressive disorders in adolescence and adulthood.¹³

As described in DSM-5, mixed features specifier can also point towards different polarity in episodes of depression, mania, and hypomania. It requires at least 3 manic or hypomanic nonoverlapping symptoms during a major depressive episode or at least 3 depressive nonoverlapping symptoms during a hypomanic or manic episode.¹⁴

A few symptoms of BD also overlap with borderline personality disorder, such as impulsivity, aggression, mood swings, affective instability, risk of substance, and high-risk behavior. Characteristic symptoms of borderline personality disorder are chronic emptiness, disturbed self-image, issues in interpersonal relationships, and self-harm behavior, while differentiating features are elevated mood, family history of bipolar, impairment in functioning, and other domains of BD.¹⁵

Assessment

In children and adolescents, we need to screen for current and past mania, hypomania, and depression by applying DSM-5 criteria, using unspecified categories in case of shorter duration of symptoms, duly examining comorbidities, and using additional caution while diagnosing preschool children. Caregivers’ interview for current symptoms, developmental history, and the longitudinal course is vitally important along with collateral information from school, peers, and significant others, with proper knowledge about environmental factors, family history for mood disorders including their presentation, comorbidity, treatment response, etc.^1,2

Commonly used instruments for childhood depression assessment are the following: children’s depression rating scale, a quick inventory of depressive symptoms, beck depression inventory, mood and feelings questionnaire, Reynolds adolescent depression scale, etc.¹⁶ Pictorial Instrument for Children and Adolescents (PICA‑R) is useful in case of lesser expression from the child with helping through diagrammatic representation.¹⁷

Considering the developmental perspective and age-specific symptoms variation of depression in children and adolescents, the DUMPS acronym is suggested: D—Duration of symptoms, depressed mood, defiance and disagreeability, and distant or withdrawal behavior; U—Undeniable drop in educational performance/academic grades or interest in school; M—Morbid and strange behavior including covert manifestation of suicidality; P—Pessimistic attitude; S—Somatic symptoms, eg, headache, abdominal pain.¹⁰

The following are common tools used for childhood bipolar assessment: Schedule for Affective disorders and Schizophrenia in Children (K-SADS) (present and lifetime version), Child Mania Rating Scale, General Behavior Inventory, Parent Young Mania Rating Scale, Young Mania Rating Scale (youth), etc.²

Treatment

Psychoeducation

Children/adolescent and their parents should receive adequate psychoeducation in the following areas—explaining about signs and symptoms of illness, the impact of untreated disease, the role of family, peers, and school, addressing common misconceptions, explaining caution with antidepressants, and managing the suicidal risk with close supervision, high-risk management, safety plan, etc, provide information about etiology, treatment modalities, risk of relapse, communication pattern, adaptive coping, and lifestyle measures and addressing other comorbid illness (physical, psychological, substance).¹⁰

Phases of Treatment

The goal of management is to achieve remission, promote social adjustment, improve quality of life and family functioning, and prevent the relapse and recurrence of symptoms, as depicted in Figure 1.¹⁰

Figure 1.

Source: This figure has been taken from Clinical Practice Guidelines of Indian Psychiatric Society, which is in open domain to use and adapt.

Algorithm of Acute Phase for Depression in Children and Adolescents¹⁰

As per the Clinical Practice Guidelines of the Indian Psychiatric Society, Figure 1 depicts an acute phase treatment approach to treat depression in children and adolescents, emphasizing the preference for psychotherapy in mild to moderate depression and antidepressants, preferably SSRI in severe depression. In case of lack of response with SSRI, other antidepressants such as venlafaxine, mirtazapine, bupropion, etc, remain effective options for pharmacotherapy.¹⁰

Continuation phase treatment suggests continuing antidepressant therapy or psychotherapy or a combination of both for 6 months to 1 year after the acute phase treatment and achieving clinical remission as they have a greater risk for relapse and recurrence and, after that, need to monitor for relapse of symptoms. Accordingly, plan to discontinue the treatment in case of no history of depression or plan for maintenance treatment as specified.

Maintenance phase treatment is sometimes advised based on the number of previous episodes (consider in the case history of 2-3 episodes), the severity of the episodes in the form of suicidality, psychotic features, significant impairment, and preference of individual and family. Duration of maintenance medication varies from 3 years to and lifetime depending on risk and clinical factors.¹⁰

Pharmacotherapy for Depression

Fluoxetine (for >8 years old) and Escitalopram (>12 years old) are the only 2 SSRIs approved for depression in children and adolescents. Meta-analysis of SSRI trials in youth reported the superiority of SSRI to placebo (response rate 60% AD vs 49% placebo).¹⁸ Food and Drug Administration (FDA) directs to monitoring for clinical worsening and suicidal thinking and behavior in individuals below 25 years of age on antidepressant medications.

Meta-analysis of 27 trials on pediatric major depression reported a comparable risk of suicidality in youth in the antidepressant group (3%) and placebo group (2%). The pooled absolute response rate was 61% in the antidepressant group and 50% in the placebo group. For the positive response to the antidepressant number needed to treat (NNT) was 10, and for the event of suicidality number needed to harm was 112.¹⁸

Psychotherapy for Depression

Cognitive Behavior Therapy (CBT)

CBT attempts to correct cognitive distortions and behavioral deficits associated with depression. Components of CBT in children and adolescents with depression include psychoeducation about symptoms and illness, mood charting, mastery and pleasure activity scheduling, behavioral activation, and cognitive restructuring.¹

The goals of CBT are the following: to help patients identify the link between mood, thoughts, and behavior or activities in their life by challenging their negative beliefs and increasing adaptive strategies such as behavioral activation; to understand negative or unhelpful thoughts, with learning to develop rational thoughts and cognitive restructuring; to equip the children and adolescents with social skills, communication, assertiveness, and skills for handling interpersonal relationship issues.¹⁹

The CBT group recovered more (67%) than the wait-listed (48%). CBT group-greater remission (65%) vs supportive therapy (39%). At 2 years, there was no significant difference among different psychotherapies. Overall, adolescents had a better response than children with depression. Antidepressants (AD) with CBT group had better response compared to other groups (AD+CBT>AD>CBT>Placebo).²⁰

Interpersonal Therapy (IPT)

IPT emphasizes the association of depressive symptoms with interpersonal relationship issues. It focuses on 4 key areas—loss, interpersonal disputes, role transition, and interpersonal deficits. Specific IPT module has been designed for adolescents (IPT-A). IPT-A is a manual for depressed adolescents, adding key areas to address developmental issues—peer pressure, authority figures, relationship issues, and parental separation. Parents of adolescents are also included in therapy to educate them about these associations and their implications. Interpersonal therapy (IPT-A) and family-focused therapy are manual-based therapies with promising results in adolescents.²¹

Meta-analysis of psychotherapy found a small effect size (0.34) in children and adolescents with depression. Psychotherapies are helpful in the short term, but more long-term strategies are essential for addressing depression in youth. In general, psychoeducation, supportive therapy, and family and school involvement are paramount in managing children and adolescents with mood disturbances.¹

Treating Adolescent Depression Study

Treating Adolescent Depression Study (TADS) study compared fluoxetine alone, CBT alone, or combined in adolescent depression. A combination of CBT and fluoxetine had a greater response rate (71%), compared to fluoxetine alone (61%), and CBT alone (35%). The remission rate was more significant with combination treatment (37%) than with other treatment groups (fluoxetine—23%; CBT—16%).²²

Treatment of SSRI-Resistant DepressionIn Adolescents (TORDIA)

The TORDIA study recruited 334 adolescents diagnosed with a moderate depressive episode who did not respond to an adequate trial of SSRI. They were randomized to receive a different SSRI or venlafaxine, with or without CBT, for 24 weeks. At 12 weeks, CBT with venlafaxine or SSRI responded better than medication alone, although who received SSRI had a more rapid decline in depressive symptoms and suicidal ideations as per self-report compared to the venlafaxine group.²³

Electroconvulsive Therapy

According to the Mental Health Care Act (MHCA-2017), for the use of modified electroconvulsive therapy (ECT) in minors, the clinician should obtain the prior permission of the Mental Health Review Board and the guardian’s informed consent. ECT is an important alternative for children or adolescents with severe depression who fail to respond to 2 adequate antidepressant trials or with severe suicidality, catatonia, and refusal to food and fluids.¹⁰

Pharmacotherapy for Bipolar Disorder

Following drugs have FDA approval for BD in adolescents—Lithium, CPZ, Olanzapine, Quetiapine, Risperidone, Aripiprazole, Asenapine, and in children (10–17 years)—Risperidone, Aripiprazole, Quetiapine, Asenapine.

Literature is mixed about the effectiveness of pharmacological options as some studies reported comparable results with monotherapy with lithium, valproate, carbamazepine with second-generation antipsychotics (risperidone, aripiprazole, quetiapine, olanzapine, asenapine, ziprasidone, and cariprazine) in manic/mixed episodes.^24,25

Treatment of Early Age Mania study (TEAM study) compared the efficacy of Lithium, Divalproex, and Risperidone and reported Lithium response (35.6%) was a little better than placebo response (25-30%) as reported in industry-sponsored trials. Divalproex (24%) is comparable to placebo (23%) in Youth bipolar. SGA has shown a 45% to 65% response rate with NNT 2.6 to 5 and a larger effect size with SGA than mood stabilizers (ES 0.65).^26,27

General principle to manage comorbid psychiatric disorders with bipolar is to prefer psychosocial management and consider pharmacological treatment in case psychosocial management fails or morbidity adversely affects the functioning or academics..²⁸

Psychosocial Management

Intervention strategies emphasize treatment adherence, addressing environmental stressors, including social rhythm, interpersonal issues, relationship with parents and peers, timely identification of symptoms and early warning signs to prevent further episodes and problems, and teaching adaptive coping and problem-solving skills. The following models have evaluated in children and adolescents with BD: family psychoeducation, family-focused therapy for adolescents, and child and family-focused CBT for younger children.²

Factors Increasing The Risk of Depression to Bipolar Shift

The following factors increase the risk of conversion of depression to BDs: earlier age of onset (before the age of 25 years), in presence of psychotic symptoms, atypical depression (eg, hyperphagia, hypersomnia), a greater number of depressive episodes (3 or more), family history of BDs, induction of hypomanic symptoms with antidepressants, mixed features, comorbid substance use disorder, migraine, and poly morbidity.¹⁴

The Course of Childhood Depression and Bipolar

Childhood depression is recurring, with an average episode duration of about 8 months, with around a 40% probability of recurrence in 2 years and a 60% likelihood in adulthood.²⁹

In childhood BD, about 10% to 20% of children have onset before age 10. Overall, up to 60% of individuals report onset before age 20. BD in adults starts with childhood depressive and anxiety disorders.³⁰

Children with prepubertal-onset bipolar had more chronic symptoms, polarity changes, and longer subsyndromal mood symptoms than those with post-pubertal-onset.^31–34 Most (80%) experience recurrences despite ongoing treatment.³⁰ Adolescents with bipolar have greater suicidal ideation and attempts and substance abuse with social and academic problems.^31,32,35

In childhood, BD outcome is less favorable at the earlier onset, presence of rapid mood fluctuations, psychosis, mixed episodes, comorbid disorders, and parental psychopathology.¹¹ Pre-pubertal onset BD is 2 times less likely to recover than post-pubertal onset of BD.³⁰

To conclude, the presentation of pediatric depression varies with age; hence, assessment should be in line with psychological and cognitive development. Non-episodic irritability is not characteristic of mania, as it generally progresses to anxiety and depression in adulthood. Timely diagnosis and multifaceted treatment approaches are vital to reduce and preventing mood episodes in high-risk children and children in the general population.

Pediatric mood disorders are associated with increased risk for suicidality, substance abuse, and academic, family, and social difficulties, stressing the need for timely identification and comprehensive treatment.

Therefore, well-designed, large-sample, multisite studies in the community, including high-risk groups, are vitally important for identifying early presentations and biomarkers that can guide effective prevention. Longitudinal studies with advanced technological and multidimensional considerations are needed to understand better etiological and mediating factors and specific, individualized treatment options and prevention strategies in children and adolescents.

Footnotes

Declaration of Conflicting Interests

The author declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Funding

The author received no financial support for the research,authorship,and/or publication of this article.

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Identifying and Managing Affective Disorders in Children and Adolescents

Abstract

Keywords

Epidemiology

Nosology

Depression

Manic Episode

Hypomanic Episode

The Presentation Across Ages and Types

Depression

Bipolar Disorder

Concerns and Comorbidity

Differential Diagnosis

Assessment

Treatment

Psychoeducation

Phases of Treatment

Algorithm of Acute Phase for Depression in Children and Adolescents 10

Pharmacotherapy for Depression

Psychotherapy for Depression

Cognitive Behavior Therapy (CBT)

Interpersonal Therapy (IPT)

Treating Adolescent Depression Study

Treatment of SSRI-Resistant DepressionIn Adolescents (TORDIA)

Electroconvulsive Therapy

Pharmacotherapy for Bipolar Disorder

Psychosocial Management

Factors Increasing The Risk of Depression to Bipolar Shift

The Course of Childhood Depression and Bipolar

Footnotes

Declaration of Conflicting Interests

Funding

References

Algorithm of Acute Phase for Depression in Children and Adolescents¹⁰