Treatment of Pediatric Bipolar Disorder: A Review

Abstract

Aim

To review the diagnosis and the pharmacologic and psychosocial interventions for pediatric bipolar disorder (PBD).

Methods

A comprehensive literature review of studies discussing the diagnosis and treatment of PBD was conducted.

Results

A context for understanding controversies and difficulties in the diagnosis of PBD is provided. An evidence-based assessment protocol for PBD is reviewed. The evidence for the following three categories of pharmacologic interventions are reviewed: Lithium, antiepileptics, and second generation antipsychotics. Algorithms for medication decisions are briefly reviewed. Existing psychosocial treatments and the evidence for those treatments are also reviewed.

Conclusion

Despite recent developments in understanding the phenomenology of PBD and in identifying pharmacologic and psychosocial interventions, critical gaps remain.

Introduction

Bipolar disorder is a chronic, impairing disorder that is characterized by significant disturbance in mood, as well as grandiosity or unstable self-esteem, hypersexual behavior, a decreased need for sleep, poor judgment, racing thoughts, and pressured speech. Bipolar disorder is associated with substantial impairments, economic distress, chronic and debilitating medical conditions, and a 10 to 20 times increased risk for suicide.^1–3 Bipolar disorder is the 6^th leading cause of disability in adults⁴ and is associated with a 10 to 20 times increase in risk for suicide when compared to the general population in the United States.³

Prior to the mid 1990’s, bipolar disorder was rarely diagnosed in children and adolescents. Even on psychiatric inpatient units, which arguably provide treatment to the most acutely disruptive and affectively dysregulated youth, only 10% of child and adolescent discharges in the United States (US) in 1996 had a primary diagnosis of bipolar disorder.⁵ In the later part of the 1990’s, however, increased attention in the academic literature was directed towards bipolar disorder in children and adolescents. Beginning in 1995, articles began to appear in the academic literature that suggested bipolar disorder manifests differently in children than adults, and that it is often underrecognized and undertreated.^6–9 In 1997, the American Academy of Child and Adolescent Psychiatry released practice parameters for the treatment of bipolar disorder in children and adolescents.¹⁰ By 2004, the proportion of US inpatients discharged with a bipolar disorder diagnosis increased to 34.11% for children and 25.86% for adolescents.⁵ A similar trend was found in less acute treatment settings; outpatient visits with US physicians for pediatric bipolar disorder increased by 40-fold from 1994 to 2003.¹¹

The increase in the diagnosis and treatment of pediatric bipolar disorder (PBD) has raised concerns of overdiagnosis of the disorder among children and adolescents, although some argue that it remains underdiagnosed.^{12, 13} Concerns over the diagnosis of PBD stem from disagreements over what symptoms constitute PBD.^{13, 14} Although no child-specific criteria for bipolar disorder are provided in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM),¹⁵ alterations from the standard criteria have been proposed.^{6, 8, 16} For example, it has been proposed that bipolar disorder in children and adolescents is characterized by less clearly defined mood episodes, shorter duration of these episodes (e.g., ultradian cycling), and different hallmark symptoms (e.g., elevated mood vs. irritability) than in adults.¹⁶

The disagreements over what characterizes PBD typically fall into two camps: the “narrow” and “broad” phenotypes of PBD.¹⁷ The “narrow” phenotype is defined by recurrent episodes of major depression and mania, with manic symptoms including elated/expansive mood and grandiosity. Yet even a strict focus on manic symptoms as a sole indicator of PBD can be problematic. A recent study of youths with elevated symptoms of mania indicates that while these youths have an increased risk for PBD, 75% of them met diagnoses other than PBD (e.g., attention-deficit/hyperactivity disorder [ADHD], oppositional defiant disorder, conduct disorder).¹⁸ Indeed, the authors suggest that elevated mania may be a better indicator of severe psychopathology rather than a specific marker for PBD.

The “broad” phenotype of PBD is characterized by chronic, severe mood dysregulation and hyperarousal.¹⁹ Although the mood states in the broad phenotype may evidence episodic variations, they are unlikely to be of the intensity or duration necessary to meet criteria for bipolar disorder (type I or II), as defined by the DSM-IV.¹⁵ Debate remains in the literature as to the inclusion of the “broad” phenotype in the bipolar spectrum (e.g. Bipolar Disorder Not Otherwise Specified) or as a distinct diagnostic category (e.g. Severe Mood Dysregulation or Temper Dysregulation Disorder with Dysphoria).^{20, 21}

Even assuming a consistent and agreed-upon definition of PBD, diagnosis remains challenging.^{22, 23} Developmental differences can make the separation of normative behavior and the symptoms of bipolar disorder challenging. Further, the overlap of symptoms as well as the co-occurrence of bipolar disorder with other disorders (e.g., ADHD, disruptive behavior disorders) complicates differential diagnosis. Finally, the variability in symptom presentation across mood states can lead to misdiagnosis, especially when there is limited access to multiple reporters. For example, without an accurate report of current presentation and past history, bipolar symptoms may present as severe ADHD or major depressive disorder.

Diagnosing PBD

Despite the difficulties in diagnosing PBD, appropriate treatment of bipolar disorder in children and adolescent is predicated on an accurate diagnosis. Even among adults, bipolar disorder may be easily misdiagnosed.²⁴ Misdiagnosis of bipolar disorder can delay the provision of appropriate treatment, resulting in either no treatment or the application of ineffective and even harmful treatment.²³ As such, a careful diagnosis of bipolar disorder is critical for determining an appropriate and effective treatment plan.

To facilitate an accurate diagnosis of PBD, the lead author worked with Dr. Eric Youngstrom of the University of North Carolina, Chapel Hill to develop an evidence-based assessment protocol. This protocol was developed at Alexian Brothers Behavioral Health Hospital to improve the reliability of diagnoses of PBD across psychiatrists. The protocol incorporates existing evidence-based approaches to the assessment of PBD²⁵ while also remaining flexible to accommodate a variety of complex clinical presentations.

The Alexian Brothers diagnostic protocol for PBD includes 5 steps: (1) screening for mania; (2) establishing an actuarial estimate of the likelihood of PBD; (3) evaluating diagnostic criteria with high specificity to PBD; (4) obtaining evidence of episodes; and (5) extending the window of assessment.

In the first step, a measure is used to screen for the presence of mania. The protocol recommends the use of the parent version of the Child Mania Rating Scale (CMRS), which is the first rating scale designed and tested specifically to screen for PBD.²⁶ The CMRS includes 21 developmentally specific items that correspond to DSM criteria for bipolar disorder. A 10-item version is available and demonstrates similar sensitivity and specificity.²⁷ Both versions of the CMRS have excellent psychometric properties and are effective as an initial screening tool for PBD.

In the second step of the protocol, the results of the screening measure and additional information (e.g., family history of bipolar disorder) are used to obtain a probability estimate of PBD. The probability estimate of PBD is obtained through the use of a nomogram, which uses Bayes’ theorem to estimate the probability of a diagnosis based on test findings or clinical observations.^{28, 29} The nomogram, which functions like a probability “slide rule,” assists the clinician in combining information about risk without having to rely on mathematical calculations. A detailed description of how to use the nomogram to obtain a posterior probability estimate of PBD is available elsewhere.³⁰

The third step in the protocol involves evaluating symptoms to determine eligibility for a mood episode. Determining if a child or adolescent has a manic episode is complicated by the controversies discussed earlier regarding what symptoms define mania for children and adolescents. The Alexian Brothers protocol recommends that clinicians focus on those criteria that are highly specific to bipolar disorder, and avoid focusing on criteria that overlap with other criteria. Specifically, we recommend that clinicians focus on the following high-specificity symptoms:

1. Decreased need for sleep. For example, a child may refuse to go to bed, or play, sing, or watch television late into the evening/early morning. An adolescent may play video games, watch television, talk or “text” on the phone, or sneak out of the house. Despite substantially less sleep than usual, the child or adolescent denies feeling tired in the morning.

2. Unstable self-esteem and grandiosity. For example, the child or adolescent may make unsubstantiated statements that indicate inflated self-esteem or grandiosity beyond what is expected for her or his developmental level. The inflated self-esteem or grandiosity should fluctuate with mood episodes, and should be in contrast with low self-esteem or feelings of worthlessness during depressive episodes.

3. Hypersexuality. This symptom is characterized by pleasure-focused sexual behavior that is either developmentally atypical or unusual and uncharacteristic of the child or adolescent. The hypersexuality should fluctuate with mood episodes.

4. Elated Mood: For example, the child or adolescent may demonstrate excessive and developmentally inappropriate excitability, silliness, and giddiness, and may demonstrate uncontrollable laughter and excessive joking. They may describe feeling “overwhelmed” by their affective experiences.

5. Pressured Speech and Racing Thoughts: Children with this symptom may indicate that their mind is going so fast that they cannot stop it and their mouth cannot keep up. Parents may describe their child and adolescent as constantly talking, never letting others have a say, domineering conversations, and constantly seeking attention by talking or “entertaining” excessively at home or school.

6. Goal-directed activity: For example, parents may identify their child or adolescent as constantly fiddling with everything at home and making a mess. Goal–directed behavior is also possible, such as constantly feeding the dog, playing games, or fighting with siblings. Teachers may see a flurry of academically-oriented activity, although the activity may not be productive or of high-quality. Children may describe experiencing “crazy maniacal spells.”

Of note, we do not include irritable mood or aggressive, hostile behavior in the list of highly specific symptoms critical to identifying PBD. Although irritability and aggression is common among children with PBD, they are also common symptoms of many psychiatric disorders, and therefore lack specificity. Further, irritability without elation or expansive mood is found in only 10% of youths with PBD.³¹ When irritability is present, we recommend that it be used to indicate the severity of the disorder, not the presence of the disorder. Irritability can be the most disruptive symptom for youths and their families, and therefore indicates a more severe case of PBD.

The fourth step in the protocol involves obtaining evidence of episodes. Although debate continues over possible deviations from DSM-based criteria in the manifestation of PBD in children and adolescents, a formal diagnosis of bipolar disorder requires the identification of an index episode, be it a major depressive episode, dysthymic episode, manic episode, hypomanic episode, or mixed episode. As stated by Dr. Ellen Liebenluft of the National Institute of Mental Health (NIMH), “the key to diagnosis [of bipolar disorder] is the episodic nature of the illness.”³² Obtaining evidence for mood episodes across the lifetime requires an assessment of both current and past symptoms; relying on only a current presentation is likely to result in misdiagnosis. Use of assessment tools, such as the NIMH Life Chart, can be helpful in documenting lifetime mood episodes.

The final step is to extend the window of assessment, particularly when the clinician is not fully confident about the diagnosis or when evidence for mood episodes is unclear. Indeed, even clear evidence of elevated symptoms of mania does not mean that a child or adolescent has bipolar disorder.¹⁸ For the most accurate diagnosis, it is recommended that the window of assessment be extended, both retrospectively and prospectively, to clearly delineate changes in mood episodes.²⁵

The diagnosis of PBD is complex, especially without clear guidance from diagnostic criteria as to the developmentally-specific manifestations of mania in children and adolescents. Additional guidance for determining the diagnosis of PBD is beyond the scope of this review, and may be found elsewhere.^{23, 25, 33} Although complex and fraught with controversy, determining an accurate diagnosis of PBD is critical to the provision of effective treatment.

Prevalence of PBD

Disagreements and complexities involved with the diagnosis of PBD have contributed to a lack of authoritative data on the prevalence of PBD.³⁴ Among adults, recent epidemiologic studies indicate lifetime prevalence rates in the US of upwards of 4% for bipolar I and bipolar II, and spectrum diagnoses (i.e., bipolar I, II, Cyclothymia, bipolar NOS) up to 8.3%.^35–37 Prevalence rates of bipolar disorder in adults outside of the US vary from less than 1% in Iceland, Taiwan, Korea, and Puerto Rico, to 3.4% in Italy, 5.1% in Switzerland, and 5.5% in Hungary.³⁸ It is important to note that differences between the 4^th edition of the DSM and the 10^th edition of the International Classification of Diseases (ICD³⁹) may complicate interpretation of differences in rates across countries. The ICD has more stringent criteria than the DSM, requiring two or more episodes of mania.

Retrospective studies of adults with bipolar disorder indicate that as many as 60% of affected adults experienced symptoms of bipolar disorder before the age of 20 years old; 10–20% reported symptoms before the age of 10 years old.^40–42 Yet, among children and adolescents, prevalence rates of bipolar vary from 0.1% to 1.8% in the general population,^{35, 43, 44} although rates of the “broad” phenotype may be as high as 3.3%.¹⁹ It remains unclear if those children and adolescents diagnosed with bipolar disorder, either narrow or broad, will demonstrate continuity if bipolar disorder into adulthood. Recent results of a 4-year follow-up of youths in the Course and Outcome of Bipolar Youth study indicate that 80% of those with bipolar spectrum disorders fully recover about 2.5 years after the onset of the disorder; however, approximately 60% subsequently have at least one recurrence within 1.5 years after full recovery.⁴⁵ Additional longitudinal studies, especially those that track youths into emerging and young adulthood, will help to clarify how symptoms progress across the lifespan.

Treatment of Pediatric Bipolar Disorder

Treatment of PBD requires a multimodal approach that incorporates pharmacologic and psychosocial interventions.⁴⁶ Although medication is the foundation of any treatment approach to PBD, psychosocial approaches are critical.

Pharmacologic Interventions

Pharmacologic agents traditionally used to treat bipolar disorder in adults are increasingly being used for children and adolescents. Evidence supporting the effectiveness of these medications is increasing; however, significant gaps remain. Especially absent are prospective studies on the treatment of PBD. Although lithium and several second generation antipsychotics have been approved by the US Food and Drug Administration (FDA) for use with PBD, there are currently no US FDA approved medications for treating bipolar disorder in youths under age 10.

A majority of pharmacologic trials with children and adolescents have focused on the treatment of bipolar mania.⁴⁷ The pharmacologic agents that are typically used to treat mania in youths include lithium, antiepileptic drugs with mood stabilizing effects, and second generation antipsychotic (SGA) medications. Because few large-scale, prospective studies have examined pharmacologic treatment for PBD, many of these medications are used without specific US FDA approval for PBD.

Lithium

Lithium has long been used as a pharmacologic treatment for adult bipolar disorder, specifically to address symptoms of mania. Lithium was the first medication to be approved by the US Federal Drug Administration (FDA) for the treatment of mania in bipolar disorder for youths ages 12–17 years. Despite being the first agent to be approved for adolescents with bipolar disorder, few studies have specifically evaluated the efficacy of lithium in the treatment of PBD. Indeed, the long history of lithium use with adult bipolar disorder likely influenced the decision to approve it for adolescents.

In the first double-blind, randomized, placebo-controlled study of treatment of lithium with PBD, Geller and colleagues examined 25 youths ages 12 to 18 years and diagnosed with bipolar I, bipolar II, mania or major depressive disorder with risk of future bipolar disorder.⁴⁸ All of the participants also met criteria for substance dependence. Nearly half of the participants in the treatment group were characterized as responders, compared to only 8% of the control group.

Kafantaris and colleagues used a discontinuation paradigm to examine lithium as a treatment for acute mania in a group of adolescents who initially responded to lithium during an open-label phase of the study.⁴⁹ The open-label phase included 100 adolescents presenting with acute mania or a mixed episode of bipolar disorder. Results of the open-label phase indicated that nearly two-thirds of the sample responded after 4 weeks of treatment, with over a quarter of the adolescents achieving remission.⁵⁰ In the double-blind, placebo-controlled phase, those adolescents who initially responded to lithium were randomly assigned to either lithium or placebo. Results indicated that both lithium and placebo had similar rates of symptom exacerbation (52.6% for lithium; 61.9% for placebo) over the course of the 2-week trial. Despite promising findings in the open-label phase, a large treatment effect for lithium was not found for acute mania with adolescents in the continuation phase.⁴⁹

A recent randomized controlled study examined the efficacy of lithium in the treatment of severe mood dysregulation, sometimes considered a broad phenotype of bipolar disorder.⁵¹ Twenty-five youths ages 7 to 17 years were randomized to a lithium treatment group or a control group. Similar to the findings of Kafantaris and colleagues, no significant differences in outcome measures were found between the lithium and placebo groups at the end of the 6-week trial.

An open trial study of 27 adolescents with bipolar I disorder examined response to lithium during an acute depressed episode.⁵² A large effect size of 1.7 was found for the reduction of symptoms of depression, with 48% of the sample showing response, and 30% showing remission. This study suggests that lithium can be effective in treating acute episodes of depression in adolescents with bipolar I disorder; however, given the findings of Kafantaris et al. (2004), controlled studies are still needed.

Antiepileptics

The use of antiepileptic agents to treat PBD has received more attention in the literature than has lithium. Carbamazepine, divalproex sodium, lamotrigine, oxcarbazepine and topiramate are the specific antiepileptics agents that have been examined in children and adolescents with bipolar disorder.

There is some support for the use of carbamazepine in the treatment of PBD.⁵³ For example, a recent open-label trial of extended-release carbamazepine with 27 children (ages 6–12 years) with bipolar disorder demonstrated significant improvements in symptoms of depression, ADHD, and psychosis. Significant improvements in symptoms of mania were also observed; however, improvements were modest and the manic symptoms did not fully resolve.⁵⁴

Less impressive results were found with oxcarbazepine, an analogue of carbamazepine. A multi-center, double-blind, randomized, placebo-controlled trial with 116 youths ages 7 to 18 years with bipolar I disorder found that oxcarbazepine was not superior to placebo after 7 weeks of treatment.⁵⁵ Of note, 19% of the treatment group compared with 4% of the placebo group discontinued the study due to adverse events.

Little is known about the efficacy of topiramate in treating PBD. A retrospective chart review indicated a 73% response rate with topiramate for 26 adolescents with bipolar I disorder.⁵⁶ In a double-blind, placebo-controlled trial of 56 youths ages 6–17 years with bipolar I disorder, topiramate demonstrated preliminary evidence of improvement in symptoms; however, the trial was discontinued prematurely after trials with adults with bipolar disorder failed to demonstrate efficacy.⁵⁷ More recently, a double-blind, randomized trial of 120 Iranian youths age 12–18 years found that topiramate resulted in a remission rate of only 18.6% on a measure of mania.⁵⁸

Three open-label trails suggest that lamotrigine may be an effective treatment of PBD.^59–61 For example, one of the open-label trials, which included 46 youths ages 8–18 years with bipolar I and bipolar II disorders, found a response rate of 72% for manic symptoms and 82% for depressive symptoms.⁶¹ This trial also found a remission rate of 56%, although 3 of the subjects who remitted by week 8 relapsed by week 14. A recent open-label trial of lamotrigine with 39 youths ages 12–17 years found that lamotrigine was associated with statistically significant improvement in symptoms of mania, depression, ADHD, and psychosis.⁵⁹ Although these results are encouraging, placebo-controlled, randomized, double-blind studies are needed to better evaluate the efficacy of lamotrigine for PBD.

Substantially more studies have examined divalproex sodium in the treatment of PBD than other antiepileptics. Findings from open-labels are encouraging.^62–64 For example, in a 6-month open-label trial of 34 youths ages 5–18 years with mixed mania, divalproex sodium was associated with a 73.5% response rate and a 52.9% remission rate for manic and depressive symptoms.⁶⁵ A separate open-label study found 61% of 22 youths ages 7 to 19 years demonstrated improvement in mania symptoms on divalproex.⁶⁴ It is important to note that while the authors of this study planned to follow the open-label phase with a double-blind, placebo-controlled phase for responders, too few participants remained in the study. Reasons for drop out from the study included the ineffectiveness of divalproex, intolerance to divalproex, and noncompliance.⁶⁴

Controlled studies suggest that divalproex may be most effective in the treatment of acute episodes of mania in bipolar disorder, and less effective as a continuation therapy or for prevention of relapse. For example, in a 5-year, double-blind, placebo-controlled study of divalproex with youths ages 5–17 years, Findling and colleagues found no clinically meaningful difference between divalproex and placebo in the treatment of youths with bipolar disorder NOS or cyclothymia.⁶⁶ A separate double-blind, randomized, placebo-controlled trial of the extended-release version of divalproex with 150 youths ages 10–17 years with bipolar 1 disorder found no superiority of divalproex over placebo after a 6-month treatment period.⁶⁷

Second Generation Antipsychotics

A greater number of studies have examined the use of second generation antipsychotics (SGA) for the treatment of PBD. The US FDA has approved several SGA agents for the treatment of bipolar disorder in children and adolescents. Risperidone (10–17 years old) was the first SGA to receive approval in 2007, followed by olanzapine (13–17 years old), aripiprazole (10–17 years old), and quetiapine (10–17 years old).

Several open-label trials, case-series, and chart review have demonstrated the effectiveness for a variety of SGA medications for PBD and are reviewed in depth elsewhere.⁴⁷ In contrast to lithium and antiepileptics, randomized, placebo-controlled trials also support the efficacy of SGA medications. For example, a multi-center, placebo-controlled, randomized, double-blind trial of youths ages 13–17 years with an acute manic or mixed episode found that participants treated with olanzapine had a response rate of 44.8% and a remission rate of 35.2%, compared to 18.5% and 11.1%, respectively, for those treated with placebo.⁶⁸ A randomized, placebo-controlled, double-blind trial of risperidone with youths 10–17 years of age who were diagnosed with bipolar I disorder and experiencing an acute manic or mixed episode demonstrated response rates of 59–63% (depending on dose) and remission rates of 43%, compared to 26% and 16%, respectively, with placebo.⁶⁹ Aripiprazole was the focus of two randomized controlled studies. In the first study, aripiprazole resulted in a response rates of 63% compared to 26% with placebo for 10–17 year olds with bipolar I disorder.⁷⁰ In the second study, which included 33 Brazilian youths ages 8–17 years diagnosed with bipolar disorder comorbid with ADHD, aripiprazole resulted in a response rate of 89% compared to 52% with placebo.⁷¹

Although less controlled studies indicate that quetiapine may be effective with PBD, a double-blind, placebo-controlled trial of 32 youths ages 12–18 years with bipolar disorder experiencing a depressive episode failed to show superiority of quetiapine over placebo.⁷² A randomized controlled study of ziprasidone for PBD has yet to be published; however, Delbello and colleagues presented on a randomized controlled study of ziprasidone with PBD at the 2008 meeting of the Society of Biological Psychiatry. This study of 237 youths ages 10–17 years with bipolar I disorder found a statistically significant effect for ziprasidone over placebo, with a moderate effect size of 0.48.⁷³

Comparative Studies

Studies have also compared pharmacologic agents against each other. Among mood stabilized, available evidence suggests that divalproex sodium may be more effective than carbamazepine⁷⁴ and oxcarbazepine.⁷⁵ Significantly greater improvements in symptoms of mania, however, are generally found with SGA over lithium and antiepileptics such as divalproex.^{73, 76} Although SGA appear to have superior efficacy to mood stabilizers, and there is some evidence that SGA may be better tolerated than some mood stabilizers,⁷⁶ SGA are also associated with greater weight gain and somnolence than mood stabilizers.⁷³

Combined Psychotropics

More than half of patients with PBD will not respond sufficiently to a single mood stabilizer.^{56, 77, 78} As such, it is commonplace for youths with PBD to be on more than one medication. In a chart review of 53 youths with bipolar disorder treated in a specialty clinic, 77% of cases were treated with more than one psychotropic medication, with an average of 3 psychotropic medications per patient.⁷⁹

Dr. Mani Pavuluri and colleagues at the University of Illinois at Chicago developed an evidence-based pharmacotherapy algorithm to assist with pharmacologic decisions for PBD.⁸⁰ Dr. Pavuluri’s algorithm consists of four steps: (1) prescription hygiene, (2) mood stabilization, (3) addressing break-through symptoms, and (4) problem solving. In the prescription hygiene step, the goal is to determine what prior medications were helpful, ineffective, or worsened symptoms, and to discontinue ineffective and potentially confounding medications (e.g., serotonin reuptake inhibitors, stimulant medications). In the next step, mood stabilization is the goal. The algorithms proposed by Dr. Pavuluri and the American Academy of Child and Adolescent Psychiatry provide assistance with making decisions regarding the specific medications, combination medications, and medication sequence to choose in stabilizing the patient’s mood.^{46, 80} In the addressing break-through symptoms step, the focus is on treating symptoms beyond acute mood stabilization, such as depression, psychotic symptoms, and sleep difficulties. It is also important to address symptoms that are resistant to treatment in this step. In the last step, problem solving, the goal is to target co-occurring conditions (e.g., ADHD and anxiety) and to manage side-effects (e.g., weight gain, extra pyramidal symptoms, somnolence, and gastrointestinal symptoms).

Psychosocial Treatments

Psychosocial treatments are a necessary adjunctive treatment to psychopharmacologic interventions for PBD.⁴⁶ Given the complex presentation of symptoms in PBD, the likelihood of comorbid disorders, and the variable efficacy of psychopharmacological interventions, psychosocial treatments can be critical to improvement. As indicated in the American Academy of Child and Adolescent Psychiatry Practice Parameter for the treatment of PBD, “a comprehensive multimodal treatment approach combining psychopharmacology with adjunctive psychosocial therapies is almost always indicated for early-onset BD” (p.119).⁴⁶ Despite the clear need for psychosocial interventions in the treatment of PBD, treatments have only recently been developed and evaluated. Many therapeutic elements are common across treatments, such as the central role of psychoeducation for the family and affect regulation for the child. Although the existing treatments are in differing stages of empirical validation, they nonetheless assist with delineating the features that are critical to the effective multimodal treatment of PBD.

Psychoeducational Treatment

Dr. Mary Fristad and colleagues developed a multi-family psychoeducation groups (MFPG) and individual family psychoeducation (IFP) as adjunctive treatments for parents and school-aged children diagnosed with bipolar spectrum disorders or other mood disorders.⁸¹ Psychoeducational treatment is designed to accomplish the following goals: increase knowledge and understanding of PBD and its treatment; improve management of the symptoms of PBD and associated conditions; improve communication and problem-solving skills; and increase the child and family’s sense of support in dealing with PBD. In addition, the treatments assist parents on becoming more involved with their child’s treatment and coaches them on ways in which they can serve as effective advocates for their child.⁸²

Children are taught to develop a “toolbox” of coping skills. For example, they are taught to identify enjoyable and calming activities in each of four domains – creative, physical, social, and relaxation – that can be used to combat negative emotional states.⁸² The children are also taught skills for managing their emotions, improving their verbal and nonverbal communication skills, and controlling impulses. Family projects and workbook exercises are used to solidify the concepts, and children have the opportunity to earn redeemable points for their behavior during each session.⁸³

The MFPG format includes eight 90-minute group sessions that occur separately but simultaneously for parents and children. The treatment is highly structured, with the specific content and skills to be practiced are outlined for each session.⁸² The IFP format was developed as an individual version of MFPG to increase the accessibility of this treatment across settings and patients. In contrast to the MFPG, IFP is delivered to individual children and their parents and families.⁸⁴ The current IFP treatment protocol consists of 24, 50-minute individual sessions, 20 of which are manual-driven and 4 of which are to be used for crisis management or additional practice.⁸⁴ IFP delivers similar content as MFPG, although a module on “healthy habits” replaces the social skills practice that takes place in the group setting. The healthy habits module focuses on maintaining sleep hygiene, improving nutrition, and increasing appropriate exercise activities. This module was designed to address mania triggered by disrupted sleep patterns, weight gain associated with psychotropic medication, and depressive symptoms.⁸⁴

Fristad and colleagues conducted an initial randomized control trial of MFPG with 35 families of children ages 8 to 11 with mood disorders.⁸¹ When compared to families who were placed on a waiting list as a control group, MFPG families demonstrated increased knowledge about mood disorders, improved family interactions, improved ability to access appropriate services, and increased perceived social support.⁸¹ Children’s mood symptom severity did not, however, decrease significantly following treatment.

A subsequent randomized control trial examined the efficacy of MFPG against a waitlist control group in a sample of 165 children with mood disorders and their families.⁸⁵ Results of this study indicated that participation in MFPG was associated with improved mood symptoms and improved quality of services that were utilized. Mood symptoms were mediated by quality of services utilized, and quality of services utilized was mediated by parental beliefs and knowledge about treatment. The authors concluded that MFPG is an effective psychoeducational intervention that helps parents become “better consumers” of the mental health system, which in turn leads to improved child symptomatology.⁸⁵

Fristad and colleagues conducted a randomized control trial examining the efficacy of IFP in 20 families of children with bipolar disorder.⁸⁴ Multiple positive outcomes were observed immediately following treatment, with continued improvement at an evaluation six months later. This trial indicates that IFP treatment is associated with improved mood symptoms, family climate, and service utilization.

Family-Focused Treatment for Adolescents

Family-focused therapy (FFT), a treatment originally developed for adults with bipolar disorder,^{86, 87} has been adapted for use with adolescents. The FFT-A intervention consists of 21, 50-minute sessions (12 weekly, 6 biweekly, and 3 monthly) for a duration of 9 months.⁸⁸ This treatment involves the parents, any available siblings, and the child with bipolar disorder. The primary goal of FFT-A is to reduce symptoms through increased awareness of how to cope with the disorder, decreased levels of familial expressed emotion, and improved family problem-solving and communication skills.

FFT-A reduces the symptoms of bipolar disorder through the delivery of three treatment components: psychoeducation, communication enhancement training, and problem-solving skills training.⁸⁸ The psychoeducation component focuses on the family developing a common understanding of the symptoms, etiology, and course of the disorder. They also develop an understanding and appreciation for the importance of adherence to pharmacotherapy, as well as create a plan for relapse prevention. The communication enhancement training component includes role-playing and rehearsal to assist with the development of skills for active listening, providing positive feedback, delivering constructive criticism, or requesting changes in another person’s behavior. Finally, the problem-solving component involves teaching participants how to identify problems in daily life, generate solutions, and implement those solutions.

A 2-year randomized control trial examined the efficacy of FFT-A delivered in combination with regular pharmacotherapy in a sample of 58 adolescents with bipolar disorder.⁸⁹ All patients received pharmacotherapy, though they were randomly assigned to receive either 9 months of FFT-A or 3 weeks of “enhanced care” psychotherapy, which focused on psychoeducation. Compared with adolescents in the enhanced care condition, those who received FFT-A had shorter times to recovery from depression, spent less time in depressive episodes, and reported lower depression severity scores over the 2-year period of study.

Interpersonal and Social Rhythm Therapy for Adolescents

Interpersonal and social rhythm therapy (IPSRT) is an individual psychotherapy based on the theory that one component of vulnerability for developing bipolar disorder is instability in circadian rhythms and neurotransmitter systems involved in regulation.⁹⁰ In the IPSRT model, psychosocial stressors are hypothesized to precipitate or exacerbate bipolar episodes through their ability to disrupt social and sleep routines.

Hlastala and Frank adapted IPSRT for the treatment of adolescents with bipolar disorder. IPSRT interventions for adolescents are also designed to stabilize social and sleep routines.⁹¹ The patient is helped to explore the relationship between stressful life events, including interpersonal problems, and their mood swings; the emphasis on addressing interpersonal functioning deficits and managing affective symptoms is intended to reduce their negative influence on his or her psychosocial functioning.

A recently published open trial of IPSRT presents findings with 12 adolescents diagnosed with a bipolar spectrum disorder.⁹² The adolescents participated in IPSRT for a total of 16 to 18 sessions over 20 weeks. Results indicate that the feasibility and tolerability of IPSRT were high (only 1 dropout), as well as significant improvements in manic, depressive, and general psychiatric symptoms over 20 weeks of treatment, with effect sizes in the medium-large to large range.

Dialectical Behavior Therapy for Adolescents

Dialectical behavior therapy (DBT) is an evidence-based psychotherapy designed for adults with borderline personality disorder to address emotional dysregulation, among other symptoms.⁹³ Goldstein and colleagues adapted DBT for the treatment of adolescents with bipolar disorder.⁹⁴ The adapted intervention, which consists of 6 months of weekly 60-minute psychotherapy sessions followed by another 6 months of bimonthly sessions, has the aim of increasing and maintaining individual and family skills.

During the first six months of acute phase treatment, participants received weekly therapy, alternating between individual therapy and family skills training. The continuation phase (months 7–12 of treatment) also involves individual and family therapy, with the goal of reviewing skills and consolidating gains. Family skills training began with psychoeducation, but continued through modules on mindfulness, distress tolerance, emotion regulation, and interpersonal effectiveness. Individual therapy focused on problem behaviors, with regular homework assignments and skills coaching available by telephone.⁹⁴

A small open trial of DBT in 10 adolescents with bipolar disorder indicated that the treatment is feasible and acceptable for this patient population. Participants who received DBT evidenced decreased suicidality, non-suicidal self-injury, emotional dysregulation, and depression symptoms after treatment.⁹⁴

Child- and Family-Focused Cognitive-Behavioral Therapy

Child- and family-focused cognitive-behavioral therapy (CFF-CBT), also known as the RAINBOW Program was originally adapted from family-focused treatment as an adjunctive intervention for children ages 8–12 with bipolar spectrum disorders.^{95, 96} The treatment was designed to be developmentally specific to children ages 8–12 and is driven by the needs of the children and their families. In addition to focusing on the identified child, CFF-CBT includes intensive work with parents in order to support them in developing an effective parenting style and to meet their own therapeutic needs. Integrating psychoeducation, cognitive-behavioral therapy, interpersonal therapy, mindfulness, and positive psychology theories and techniques, the intervention is designed to be employed across multiple domains – individual, family, peer, and school – in order to address the impact of bipolar disorder on the child’s psychosocial context.⁹⁷

CFF-CBT consists of 12, 60-minute sessions that are intended to be delivered weekly over the course of 3 months. Most sessions involve both the parent and the child together, though some involve either the parent or the child individually. The key components of CFF-CBT are conceptualized by the acronym RAINBOW: Routine, Affect regulation, I can do it, No negative thoughts and live in the now, Be a good friend/balanced lifestyle for parent, Oh- how can we solve this problem, and Ways to get support. Topics covered include establishing a predictable routine, teaching behavioral management, increasing parent and child self-efficacy, decreasing negative and fatalistic cognitions, improving social functioning, engaging in collaborative problem-solving, and increasing social support.

A preliminary open trial of CFF-CBT, conducted with 34 children and young adolescents with PBD who were concurrently receiving medication management, provided preliminary evidence for the success of the intervention.⁹⁵ Youths who received the treatment demonstrated reduced symptoms of inattention, aggression, mania, psychosis, depression, and sleep disturbance. They also demonstrated significantly higher global functioning scores compared to pretreatment results.

In a subsequent maintenance model study of CFF-CBT, which was comprised of psychosocial booster sessions and continued psychopharmacology, the 34 patients who received the initial 12-session CFF-CBT treatment were followed up over a 3-year period. Results from this study indicated that patients were able to maintain the initial positive effects of treatment over 3 years with regular booster sessions and ongoing medication management; there were no significant differences between post-acute phase treatment scores and scores at years 1, 2, or 3 on any measures.⁹⁷

CFF-CBT has recently been adapted for group treatment. A preliminary study of 26 families of 6–12 year old children with PBD indicated significant improvement in manic symptoms, as well as improvement in coping and well-being. The findings suggest CFF-CBT, pharmacotherapy, is also effective in a group context.⁹⁶

A randomized controlled trial of CFF-CBT is currently being conducted by Dr. Amy West and her colleagues.

Conclusions

Children and family who suffer from PBD experience numerous impairments in social, emotional, and academic functioning.⁹⁸ Although the evidence base for effective pharmacologic and psychosocial treatments for PBD is growing, additional research and treatment development is clearly indicated. For example, longitudinal studies of the treatment of PBD are needed, both for pharmacologic and psychosocial interventions. Future research should also clarify how psychosocial interventions work as an adjunctive to psychopharmacologic interventions: do they support adherence to pharmacologic interventions, do they address symptoms not treated by pharmacologic interventions, or do they add to sustained remission and improved quality of life above and beyond pharmacological interventions? Preliminary results suggest that psychosocial interventions may add utility beyond medication or treatment as usual in addressing specific aspects of the disorder; however, more rigorous designs are needed.

Evaluating interventions for PBD is challenging. First, there continues to be disagreement about the diagnosis of bipolar disorder in children and adolescents. Indeed, the bipolar disorder spectrum includes a range of symptom profiles. The lack of specific, clear, and agreed-upon diagnostic criteria for PBD presents a significant challenge to rigorous research studies. Second, the episodic nature of PBD makes it difficult to discern results of an intervention from the natural course of the disorder. Indeed, one study found a 52% response rate with a placebo.⁶⁸ Third, medication regimens for PBD are often quite complicated, involving multiple medication combinations that require frequent adjustments to address recurring symptoms and side effects.⁷⁹ Evaluating the efficacy of both pharmacologic and psychosocial interventions in real-world conditions is a significant challenge. Finally, because of the chronic nature of bipolar disorder, it is necessary to evaluate pharmacologic and psychosocial interventions over an extended period of time.

These challenges point to the need for rigorously designed longitudinal studies that utilize large samples, often across multiple locations. Considering the substantial impairment to the patient and the significant costs to society associated with PBD, the investment in such research will likely pay off in terms of reduced impairment, disability, and morbidity.