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Recognition and Treatment of Pediatric Bipolar Disorder

Evidence-Based Psychotherapies and Nutritional Interventions for Children With Bipolar Spectrum Disorders and Their Families

Evidence-Based Psychotherapies and Nutritional Interventions for Children With Bipolar Spectrum Disorders and Their Families

Treatment guidelines recommend that psychotherapy be used in conjunction with pharmacotherapy in children with bipolar disorder. A well-established category of psychotherapy is family skill-building plus psychoeducation; 3 examples of this are family-focused treatment, psychoeducational psychotherapy, and child- and family-focused cognitive-behavioral therapy. These treatments share several common elements that are important in pediatric populations, including being family-based, providing psychoeducation on symptoms and their management, and training patients and families in emotion regulation, communication, and problem-solving skills. Clinicians may also wish to explore nutritional interventions; multinutrient complexes are experimental, and omega-3 fatty acid supplements are possibly efficacious. Nutritional interventions are particularly attractive in this patient population because of their favorable safety profile.

(J Clin Psychiatry 2016;77[suppl E1]:e04)

From the Departments of Psychiatry and Behavioral Health, Psychology, and Nutrition, Wexner Medical Center, Ohio State University, Columbus.

This article is derived from the planning teleconference series "Recognition and Treatment of Pediatric Bipolar Disorder," which was held in August and September 2015 and supported by an educational grant from Forest Laboratories, Inc.

Dr Fristad is a consultant for Wayne County, Michigan; has received grant/research support from the National Institute of Mental Health; has received honoraria from and/or is a member of the speakers/advisory boards for the American Psychological Association, Mayo Clinic, the Sensory Processing Disorders Foundation, and the International Society for Bipolar Disorders; and receives royalties from American Psychiatric Publishing, Guilford Press, Child & Family Psychological Services, and J&K Seminars.

Corresponding author: Mary A. Fristad, PhD, ABPP, Ohio State University, 1670 Upham Dr., Columbus, OH 43210 (mary.fristad@osumc.edu).

dx.doi.org/10.4088/JCP.15017su1c.04

© Copyright 2016 Physicians Postgraduate Press, Inc.

Although bipolar disorder has biological underpinnings, cognitive, behavioral, and environmental stressors can trigger or exacerbate the biological dysregulation.1 Pharmacologic treatments are effective for controlling the biological causes of mood episodes, but psychosocial treatments are necessary to address the external forces that can activate or worsen bipolar symptoms, especially in children. In addition, nutritional interventions may aid in correcting some of the pathophysiologic causes of mood symptoms.

PSYCHOSOCIAL INTERVENTIONS: RATIONALE, COMPONENTS, AND EVIDENCE

Practice guidelines2 for treating pediatric bipolar disorder recommend combining pharmacologic and psychotherapeutic interventions. Psychosocial interventions are critical in this population because children with bipolar disorder are known to experience psychosocial impairments—including academic, interpersonal, and overall functioning impairments—both during episodes and during periods of remission.3 For example, Geller and colleagues conducted a series of studies4-6 on psychosocial functioning in children with bipolar disorder. They found that, compared with children with attention-deficit/hyperactivity disorder and children with no psychiatric disorder, children with bipolar disorder exhibited greater impairments on measures of psychosocial functioning including maternal-child warmth, parent-child tension, and peer relationships.4 At 2-year5 and 4-year follow-ups,6 low maternal warmth was associated with an increased relapse rate.

clinical points

  • Include psychotherapy in the treatment plan for all pediatric patients with bipolar disorder.
  • Select an evidence-based psychotherapy that is family-oriented and contains psychoeducation about the disorder as well as skill-building in emotion regulation, communication, and problem-solving.
  • Consider recommending nutritional supplements to promote good health and potentially improve mood symptoms.
  • Watch for randomized, controlled trials of psychosocial and nutritional interventions for pediatric bipolar disorder.

Children with bipolar disorder will most likely be dealing with the symptoms of this condition throughout their lives, as will their families. Patients and families, therefore, need psychosocial and behavioral interventions that will help them manage the emotional dysregulation and potentially harmful sequelae of mood episodes. Numerous psychosocial treatment options have been explored as adjuncts to pharmacotherapy for childhood-onset bipolar disorder. While no specific psychosocial treatment has been well-established, meaning that efficacy has been demonstrated through 2 or more research groups’ independent, randomized, controlled trials, family skill-building plus psychoeducation is a class of interventions that has been shown to be well-established.7,8 Examples of these include family-focused treatment, psychoeducational psychotherapy, and child- and family-focused cognitive-behavioral therapy. Dialectical behavior therapy9 and interpersonal and social rhythm therapy10 have shown some promise for pediatric bipolar disorder but should be considered experimental until large randomized, controlled trials have been conducted.7

Efficacious psychosocial interventions have several common characteristics. They are family-based treatments and include education on symptom management for both the parents and the child. The interventions also include psychoeducation and skill development in emotion regulation. In this article, family-focused treatment (FFT), multifamily and individual family psychoeducational psychotherapy (MF-PEP and IF-PEP), and child- and family-focused cognitive-behavioral therapy (CFF-CBT) are described.

Family-Focused Treatment

Rationale. Family-focused treatment was developed in an attempt to give adolescents with bipolar disorder and their families knowledge and skills that could limit the debilitating cycles of relapse and impairment that are characteristic of this disorder.11 This treatment is informed by research showing a strong association between expressed emotion and bipolar disorder outcomes. Expressed emotion refers to the amount of criticism, hostility, or emotional overinvolvement exhibited by the patient’s caregivers. Patients with bipolar disorder who live in homes with high expressed emotion have been found to have higher rates of relapse and more severe symptoms than those who live in homes with low expressed emotion.11 Thus, FFT seeks to reduce expressed emotion through psychoeducation and skills training.

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Structure. Addressing both protective and risk factors in the family and social environment,12 FFT is delivered in up to 21 sessions over 9 months.12,13 The first sessions are devoted to psychoeducation (AV 1).11 The patient and family are taught about bipolar disorder and its treatments. Both the patient and the family are asked to share their experiences of the mood episodes and how they have affected the family. The patient is asked to begin a mood chart in which he or she monitors daily moods and sleep/wake times. The clinician explains risk and protective factors, and known stressors are identified. The psychoeducation phase of treatment concludes with the patient and family developing a "mood management plan" that involves medical and behavioral strategies to be employed when the patient’s mood or sleep patterns begin to change.

The next phase of FFT is communication enhancement training, in which the participants learn to effectively express positive and negative feelings, to be active listeners, and to make positive requests for change.12 This training is done through role-playing exercises and homework.

The final phase of FFT is problem-solving skills training. During these sessions, participants identify problems, learn to break down large problems into smaller issues, generate and evaluate potential solutions, and cooperatively select and implement solutions.12

Evidence. Although FFT has been studied most extensively in adults and adolescents,12 some studies have found FFT to be effective in younger patients. Miklowitz and colleagues14 conducted an open trial of abbreviated FFT in 13 children and adolescents (aged 9-16 years) at high risk for developing bipolar disorder. Although not diagnosed with bipolar disorder, all participants exhibited clinically significant mood symptoms at study entry and had a parent with bipolar disorder. After a year, participants displayed significant improvements in depression and hypomania scores (P < .0001 for both). Additionally, in a later randomized trial15 of 40 high-risk youths aged 9 to 17 years, participants were randomly assigned to receive either the brief FFT or up to 2 family education sessions. Those receiving FFT had faster recovery from their mood symptoms (P = .047), more weeks in remission, and better mania scores over 1 year. Thus, FFT may be a feasible and effective psychosocial treatment for children with bipolar disorder.

Multifamily and Individual Family Psychoeducational Psychotherapy

Rationale. My colleagues at Ohio State University and I developed psychoeducational psychotherapy. Our rationale for developing MF-PEP and IF-PEP was very similar to that behind FFT.16,17 We wanted to create a therapeutic program that would reduce expressed emotion and provide knowledge and skills to help patients and their families more effectively manage the symptoms and effects of bipolar disorder. We also wanted to provide therapy in a group setting because this allows families to develop a social support network and has been found to be more effective than individual therapy for extending periods of remission.18

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Structure. Psychoeducational psychotherapy can be delivered in multifamily groups (MF-PEP) and with individual families (IF-PEP).16,17 In MF-PEP, parents and their children with bipolar disorder participate in 8 therapy sessions (AV 2).16,17 Each session of MF-PEP is 90 minutes long and begins with the parents and children of all families together for brief introductory information and a weekly review. Then, parents and children split into separate groups to cover the session topic. Children end their sessions with 15 to 20 minutes of recreational interaction intended to help develop social skills and friendships. Finally, the parents and children come back together to review and discuss the project that the family should work on at home over the next week.16,17

The first 4 parent sessions are primarily didactic and include information about bipolar disorder and its symptoms and comorbidities.16,17 Parents learn about various forms of treatment (biological, psychological, social), including different classes of medications, the symptoms they target, and side effects. Parents learn about systems of care such as those available in schools and in the community. They learn about how the challenges of having a child with bipolar disorder can lead to a negative family cycle, and they are given tips on how to avoid or escape common ruts. The last 4 parent sessions of MF-PEP are devoted to skill building.16,17 Parents learn problem-solving, communication, and symptom management skills.

The first 2 child sessions also provide information on symptoms of depression and mania and biopsychosocial treatments, including medications and how they are necessary for regaining health. Subsequently, children build a "tool kit" to manage their emotions, using creative, active, rest-and-relaxation, and social strategies (CARS). They learn that their thoughts, feelings, and actions are connected and that they can modify their behavior and thoughts to change their feelings. Children learn problem-solving and communication skills. Both verbal and nonverbal forms of communication are covered. At the conclusion of therapy, participants review the topics and graduate.

To meet the needs of families who prefer a more private setting for therapy, who live in smaller communities that do not have a population large enough to form a group, or who see providers in private practice or smaller clinics, IF-PEP was developed.17 Total therapist time is equivalent in MF-PEP and IF-PEP, but, instead of 8 separated parent-child groups for 90 minutes in MF-PEP, IF-PEP offers 17 to 24 50-minute sessions, with the parents and child alternating sessions. The topics covered in MF-PEP are also covered in IF-PEP, but as IF-PEP can be administered more flexibly to meet individual family needs, additional sessions to review content can be introduced, and the order of sessions can be rearranged, as needed, for families in crisis. The IF-PEP sessions also include units on healthy habits (ie, sleep hygiene, good nutrition, and age-appropriate exercise) and optional sessions focused on sibling issues and school-based intervention planning.17

Evidence. Several randomized controlled studies of MF-PEP and IF-PEP have been conducted in children with mood disorders. One study19 of MF-PEP included 35 children aged 8 to 11 years with either depressive or bipolar disorders and 47 family members. After completing therapy (versus wait-listed controls), parents reported significant increases in their knowledge of mood disorders (P < .009), positive family interactions (P < .05), and efficacy in service utilization (P < .01), and children reported significantly increased social support from their families (P < .003).19

A later study20 of MF-PEP included a larger population of children aged 8 to 11 years. Of the 165 child participants, 70% had bipolar disorder. Participants came from all types of family structures and a range of incomes. Most were male, were white, and had at least one of the following comorbid disorders: attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, or behavior disorders. The sample was divided into active treatment and wait-listed control groups. The participants who received MF-PEP showed greater improvement in symptom severity than the control group. Furthermore, they maintained this improvement for 18 months after treatment.20 In a secondary study of this patient sample, Mendenhall and colleagues21 found that the families who completed MF-PEP became better consumers of care. Participation in MF-PEP led to changes in parents’ attitudes toward treatment, which led to utilization of higher quality services. This, in turn, led to improvements in patients’ symptom severity.21 A study22 of MF-PEP in community clinics found implementation to be acceptable and feasible.

Although IF-PEP has not been studied as thoroughly as MF-PEP, I conducted a small-scale randomized, controlled trial of IF-PEP17 (N = 20 families) and found that children who participated experienced decreased symptom severity. These improvements began immediately following treatment and endured for 12 months. Improvements in family climate and service utilization were also found, suggesting that IF-PEP may be as effective as MF-PEP. More recently, in a pilot randomized, controlled trial that examined the impact of IF-PEP and omega-3 fatty acids both alone and in combination in 23 children with bipolar disorder not otherwise specified or cyclothymic disorder, my colleagues and I showed that IF-PEP alone had a medium to large effect size (d = 0.63 to 1.24) on depressive symptoms, compared with active monitoring.23

Child- and Family-Focused Cognitive Behavioral Therapy

Rationale. Pavuluri and colleagues24 conceived of CFF-CBT as an evolution of FFT. They sought to preserve the family-focused nature of FFT as designed by Miklowitz and Goldstein,13 but added components designed to address the specific developmental needs of younger children. Namely, Pavuluri and colleagues believed that an effective psychosocial treatment must address not only the dysfunctional affective brain circuitry and psychopathological characteristics of pediatric bipolar disorder but also the environmental stressors that can trigger and worsen mood symptoms.

Structure. Child- and family-focused cognitive behavioral therapy combines CBT principles with interpersonal psychotherapy for patients, and it provides direct assistance to parents for handling frustration and managing symptoms and functional impairment. The skills covered in CFF-CBT can be expressed by the acronym RAINBOW: Routine; affect regulation; I can do it; no negative thoughts/live in the now; be a good friend/balanced lifestyle; oh, how can we solve it?; and ways to get support (AV 3).24 These skills are introduced over 12 60-minute sessions of therapy, which include psychoeducation, CBT, and interpersonal skill training in problem solving.

Evidence. In a preliminary study of 34 children aged 5 to 17 years with bipolar disorder, Pavuluri and colleagues24 found that, after completing therapy, the children had experienced significant improvement in severity of mood symptoms (P < .0001) and in functioning (P < .0005) compared with pretreatment levels.24 West and colleagues conducted a randomized controlled study8 of CFF-CBT versus a control condition of usual psychotherapy among 79 children aged 7 to 13 years who had bipolar disorder. Participants received monthly posttreatment booster sessions for 6 months. Compared with the control group, the children who received CFF-CBT had significantly lower mania symptoms at posttreatment (P = .007), significantly reduced parent-reported depression at posttreatment (P = .03) and follow-up (P < .05), and significantly greater improvement in global psychosocial functioning at follow-up (P = .04).

In conclusion, psychosocial interventions for pediatric bipolar disorder are an essential element of treatment, in conjunction with medication. Psychosocial interventions should be evidence-based, should include family members, and should provide psychoeducation and strategies to improve communication, problem solving, and symptom management. However, nutritional interventions may also be relevant in children with bipolar disorder.

NUTRITIONAL INTERVENTIONS

Nutritional interventions for physical and mental illnesses were some of the earliest forms of treatment, dating back to ancient times.25 Modern medicine has come a long way, and numerous state-of-the-art treatments are available for virtually every conceivable disorder. Although the importance of proper nutrition to physical health is never questioned, the relationship between nutrition and mood has received less attention. In pediatric bipolar disorder, diet should be an important consideration because, during childhood, the brain is growing and developing rapidly.26 A child’s diet fuels this development, and improper nutrition, therefore, may have a damaging effect on brain development. Poor diet has been found to be associated with cognitive and behavioral problems.26 Furthermore, pharmacotherapy is an important part of treatment for bipolar disorder, but, especially in pediatric patients, drugs can carry a significant burden of side effects.27,28 Risks and benefits must be carefully considered,29 and clinicians should strive to use the lowest possible dose of medication and the smallest possible number of medications. Nutritional interventions have the advantage of a more favorable risk-benefit ratio than currently available pharmacotherapies,30 and they can be used in conjunction with psychotherapy and pharmacotherapy. Several vitamins and minerals such as iron, zinc, folate, and other B vitamins are involved in central nervous system functioning, particularly mood.25 Supplementing nutritional deficiencies associated with mood may therefore be helpful for improving the symptoms of pediatric bipolar disorder.

Multinutrient Complexes

Rationale. Kaplan and colleagues25 have proposed the following 4 models as potential explanations for the association between micronutrients and mood symptoms: (1) Some individuals may be born with a genetic mutation that affects brain function through altered metabolism and absorption of micronutrients, resulting in mood symptoms. (2) Hundreds of methylation reactions occur in human brains and affect numerous processes, including neurotransmitter synthesis. Mood symptoms may result from deficiencies in methylation processes. (3) Nutrition deficiencies may alter gene expression and lead to mood instability. (4) Unstable mood may result from long-latency effects of nutrient deficiencies that alter brain development.25

Evidence. The nutritional deficits contributing to mood symptoms are likely to be complex and involve a number of nutrients. Supplement formulations that contain multiple nutrients, therefore, are more likely to be effective for improving mood symptoms than single nutrient supplements.25 Several studies have examined the effect of a proprietary micronutrient formula on mood.30,31 This formula consists of 36 ingredients, including vitamins, minerals, amino acids, and antioxidants. Rucklidge and colleagues conducted an open-label, uncontrolled analysis31 of information on a manufacturer’s database for 120 children with pediatric bipolar disorder who received the micronutrient formula. The children who received the micronutrient formula experienced a significant reduction in their bipolar symptom severity after 3 to 6 months (P < .001).31 The number of children taking psychiatric medications decreased by 52%, and the number of medications taken dropped by 74%. This micronutrient formula was also examined in an open-label feasibility study by Frazier and colleagues.32 They found that, among 10 children with pediatric bipolar disorder, the 7 participants who completed 8 weeks of treatment with the micronutrient formula experienced a significant reduction in both depression and mania scores (P < .05). The supplement was also well tolerated.32,33 Randomized, controlled trials are needed to confirm these findings, but these preliminary results indicate that multinutrient complexes may be a viable treatment option for children with pediatric bipolar disorder.

Omega-3 Fatty Acids

Rationale. Omega-3 fatty acids are essential nutrients that are involved in gene expression34 and are found in the cellular membrane of all tissues, where are they are involved in signaling and communication between cells.35 Omega-3 fatty acids cannot be synthesized by the human body and must, therefore, be obtained from dietary sources. Omega-6 fatty acids are also consumed in the diet, but the ratio of omega-3 to omega-6 fatty acids has changed over time. Humans evolved on a diet with a 1:1 ratio of omega-6 to omega-3 fatty acids, but the ratio in the typical Western diet consumed today is closer to 15:1.34 This dietary imbalance between omega-6 and omega-3 fatty acids that has emerged over the past 100 years has been implicated in a number of chronic conditions, including cardiovascular disease, diabetes, cancer, and depression, among others.34

Evidence. Omega-3 fatty acids have gained a great deal of attention in depression. Fish is a rich source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),36 which are found in neural tissue and are involved in nervous system functioning. Hibbeln compared fish consumption with depression rates in several countries and found that depression rates were lower in countries with higher fish consumption.36 Noaghiul and Hibbeln37 also found lower lifetime rates of bipolar disorders in countries with high fish consumption. The correlation between fish consumption and lower rates of mood disorders has led to the hypothesis that omega-3 fatty acids might be an effective treatment for these conditions.38 Lin and Su conducted a meta-analysis38 of 10 double-blind, placebo-controlled studies of patients with mood disorders who received omega-3 fatty acids for at least 4 weeks. The meta-analysis showed significant antidepressant efficacy of omega-3 fatty acids (P = .003) in adults with depression and bipolar disorder.

Omega-3 fatty acid supplementation has been examined in studies of pediatric patients. Clayton and colleagues39 conducted a 6-week, open-label study of 18 juvenile patients with bipolar disorder. Participants received omega-3 fatty acid supplements in addition to their standard medications. After treatment, the severity of the patients’ mood symptoms had decreased and their global functioning had increased. In another open-label trial, Wozniak and colleagues40 examined 1.3 to 4.3 g/d of omega-3 fatty acid monotherapy (7:1 EPA:DHA) in an 8-week trial of 20 children aged 6 to 17 years with bipolar spectrum disorders. They reported significant decreases in both manic and depressive symptoms as measured by the Young Mania Rating Scale (P < .001) and the Children’s Depression Rating Scale (P = .002). Youth taking more than 2 g/d had greater improvements than those who took less than 2 g/d. Side effects reported in these studies were primarily gastrointestinal and mild.

Our recently completed pilot randomized, controlled trial of PEP plus 2 g/d of omega-3 fatty acids showed that combination treatment (both therapy and supplement) provided the greatest benefit to youth, with a large effect size in depressive symptoms compared with placebo and active monitoring (d=1.70, P = .018).23 As with the prior studies, side effects were uncommon and mild.

As with multinutrient supplements, the existing data on omega-3 fatty acids for pediatric bipolar disorders are currently limited. However, available evidence does indicate that supplementation might be a safe and effective adjunct to pharmacotherapy and psychotherapy. If nutritional supplements do not help ameliorate mood symptoms, they are still beneficial for overall good health. They appear to have minimal side effects, meaning that in children the risk-benefit profile is positive. Large randomized, controlled trials are needed.

CONCLUSION

Children with bipolar disorder need treatment that will allow them to control their symptoms and be able to function in numerous contexts. Pharmacotherapy alone is unlikely to achieve these goals. Different psychosocial treatment programs are available that can help not only the children with bipolar disorder but also their parents to become educated about the disorder and available treatments and to build important skills in symptom management, communication, and problem solving. Nutritional interventions such as multinutrient complexes and omega-3 fatty acid supplements may also be not only efficacious but safe adjuncts in children. Clinicians should watch for future randomized, controlled trials on psychotherapies and nutritional interventions for pediatric bipolar disorder. By using evidence-based treatment options, clinicians can help children with bipolar disorder grow up into healthy, functional adults.

Disclosure of off-label usage: Dr Fristad has determined that, to the best of her knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration-approved labeling has been presented in this article.

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References