Treating Symptoms of Bipolar Disorder in Children at Risk
At the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, one symposium was devoted to new research on predicting onset of bipolar disorder in children who have a family history of the disorder. Below are some of the findings that were reported. See previous articles for more on this symposium.
Sub-Threshold Bipolar Disorder or BP-NOS is Impairing and Requires Treatment
In research Danella M. Hafeman’s research, children with BP-NOS were almost as ill as those with bipolar I disorder (BP I) and experienced equal incidence of suicide attempts, substance abuse, other simultaneous psychiatric diagnoses, and functional impairment, clearly indicating that they were in need of treatment. About 50–65% of participants with a family history of bipolar disorder converted from diagnoses of BP-NOS to BP I, while those with BP-NOS and no family history of bipolar disorder converted to BP I at rates of about 30–48%.
Several presenters presented data showing that those with sub-threshold bipolar disorder had severe functional impairment, a high incidence of suicide attempts, and additional diagnoses including ADHD, conduct disorder, anxiety, and substance abuse.
Diagnostic Tool Can Help Identify Children with Bipolar Disorder
Researcher Amy Yule indicated that a tool called the Child Behavior Checklist (CBCL) is effective for making the diagnosis of conduct disorder in children with bipolar disorder, while researcher Joseph Biederman showed that the CBCL can also identify children with bipolar I disorder and is faster and simpler to use in clinical practice than are full structured diagnostic interviews.
Researcher Janet Wozniak found that there was a high incidence of bipolar disorder in first-degree relatives of children with sub-threshold bipolar disorder, suggesting the validity of identifying youth with sub-threshold bipolar symptoms.
As discussed above, there is also a high incidence of children with BP-NOS progressing to a full diagnosis of bipolar I or II disorder (as many as 50% of those with a family history of bipolar disorder). However, the point is not to wait for the negative effects of a full diagnosis before beginning treatment: BP-NOS itself requires treatment.
Discussion and Emerging Consensus on Treatment, Particularly of BP-NOS
Experts in the field agree that family focused therapy (FFT) or its equivalent is a crucial first step to treatment of depression, cyclothymia (cycling between depressive and hypomanic symptoms that do not meet the threshold for a diagnosis of bipolar disorder), and BP-NOS in children who are at high risk of bipolar disorder because they have a parent with the disorder.
A second area of agreement is that young people with BP-NOS should have a positive therapeutic coach (which could be a treating physician if no other person is available), who can emphasize important early steps that can improve short- and long-term health. These include maintaining a healthy diet, exercise (such as participation in school sports), the practice of mindfulness and/or meditation, and playing and practicing a musical instrument. Parental support is also critical to decreasing negative expressed emotion.
Early interventions and wellness programs that focus on these factors are part of the successful Vermont Family Based Approach, led by psychiatrist Jim Hudziak, Director of the Vermont Center for Children, Youth, and Families. Since programs like these are not widely available, treating physicians must create their own teams to provide such encouragement, and teach families how to find or establish such a support network.
School teachers should be engaged in support of the treatment of a child with bipolar disorder. Teachers should pay special attention to behavioral symptoms of an ill child. It also may be important for physicians to connect directly with teachers to ensure that children recovering from an episode of bipolar disorder receive extra time for assignments, a decreased academic burden, and other support. Researcher Manon H. Hillegers indicated that intervention by a physician will likely be listened to and believed, while parental requests alone to teachers or to the school may go ignored.
Hillegers, like researcher Lakshmi Yatham and colleagues, have found that it takes a year after a first manic episode for a child’s cognition to return to normal, so that special allowances should be made for such students even many months after they have recovered from their mania.
Positive Effects of a Brief Session of Aerobic Exercise for Sedentary Children
At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Benjamin I. Goldstein reported that a single 20-minute session of aerobic exercise (achieving 70% of maximal heart rate) was associated with improvement in cognition and in abnormalities seen on brain imaging in young people. Goldstein urged clinicians to do motivational interviews with sedentary children in their care, emphasizing the positive cardiovascular and cognitive effects of exercise. He indicated this would be more effective than a focus only on weight loss, which is much more difficult to achieve.
Family Focused Therapy Effective in Youth at Risk for Bipolar Disorder Who Have Early Symptoms
Researcher David Miklowitz developed Family Focused Therapy (FFT), in which families of young people at risk for bipolar disorder take part in therapy, learning about the illness and practicing strategies for communication and coping.
At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, Miklowitz reported findings from recent studies of youth who were at high risk for bipolar disorder because of a family history of the illness and the presence of early symptoms such as depression or cyclothymia or bipolar not otherwise specified (BP-NOS). Family focused therapy reduced symptoms. It also slowed onset of a first episode of mania and slowed the conversion to a diagnosis of bipolar I or bipolar II. These results converge with a total of 10 other positive studies of family focused therapy in different populations in children and adults. FFT or its equivalent should be made available to all symptomatic children who are at risk for bipolar disorder because of a family history of the disorder.
Potential Problems when Youth at Risk for Bipolar Disorder Take SSRIs
At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Manpreet Singh reported that in youth at high risk for bipolar disorder, 53% had an adverse event while taking a selective serotonin reuptake inhibitor antidepressant (SSRI), and 26% had a new onset of suicidality while taking an SSRI. These adverse events were associated with reduced size and increased activation of the amygdala, the brain region responsible for emotion processing. Singh concluded that dysfunction in the prefrontal-limbic network may predict adverse events in children at risk for bipolar disorder when they are given SSRI antidepressants. She urged caution in the use of antidepressants in this population. Researcher Joseph Biederman echoed this caution later in the meeting.
Quetiapine Reduced Childhood Mania, Especially in Those with Thicker Frontal Temporal Regions
In a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Melissa P. Delbello reported that six weeks of treatment with either lithium or quetiapine was effective in childhood mania, but quetiapine had a higher response rate of 71% versus 46% for lithium. Delbello found two types of structural changes on functional magnetic resonance imaging (fMRI). Some children had thicker frontal temporal regions, while others had thinning in these areas. The first group of patients had a 100% response to quetiapine, but only 53% of the second group responded to quetiapine.
In contrast, other researchers have found lithium superior to quetiapine. Vivian Kafantaris showed that patients who respond well to lithium show improvements in white matter abnormalities. Michael Berk and colleagues found that a year on lithium was superior to quetiapine on all measures including cognition and brain imaging in patients having their first episode of mania.
Lithium Effective for Maintenance Treatment of Childhood-Onset Bipolar Disorder
Evidence has been accumulating that lithium is effective in the treatment of young people with bipolar disorder. In a study by Robert Findling and colleagues published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2018, participants aged 7–17 who responded well to lithium during a 24-week study were then randomized to receive either lithium continuation (17 participants) or placebo (14 participants) for 28 more weeks.
Those who continued lithium treatment were more likely to stay in the study. Participants who discontinued the study mostly reported that they did so due to re-emergence of their mood symptoms (mostly in the placebo group).
Lithium was well-tolerated and was not associated with any more weight gain than placebo. This study adds to the growing literature on the effectiveness and tolerability of lithium both acutely and in maintenance treatment in childhood bipolar disorder.
Lithium Better than Other Mood Stabilizers for Youth with Bipolar Disorder
A new study by Danella M. Hafeman and colleagues finds that lithium is superior to other mood stabilizers in young people. The data in this case come from 340 youth aged 7–17 who participated in a study known as Course and Outcome of Bipolar Youth (COBY).
At each visit over an average of 10 years, participants reported medications taken, symptoms they had experienced, etc. during the preceding six-month period. During times that participants had taken lithium (compared to other mood stabilizers) they were older, on fewer antidepressants, and they were less likely to have an anxiety disorder.
Those participants who took lithium had half as many suicide attempts, fewer depressive symptoms, less psychosocial impairment, and less aggression than those who took other mood stabilizers.
The researchers concluded, “Findings are consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning. Given the paucity of evidence regarding lithium in children and adolescents, these findings have important clinical implications for the pharmacological management of youth with bipolar disorder.”
Editor’s Note: Lithium should especially be considered in those with a family history of mood disorders, and in particular in those with a family history of good response to lithium. Lithium is under-prescribed in both adults and children and should be given much higher consideration in light of the multiple benefits it provides in addition to mood stabilization. These include maintenance of memory, increases in longevity (perhaps based in its ability to increase the length of telomeres, the bits of protective material at the end of DNA strands that deteriorate with age and illness), and neuroprotection against loss of gray and white matter volume in the brain, which often occurs in mood disorders.
Small Percentage of Patients Do Not Re-Respond After Stopping Lithium
Researcher Ralph Kupka reviewed the literature on the small subgroup of patients who do well on long-term lithium treatment, stop taking the drug, suffer a relapse, and then fail to re-respond as well as they had (or, in some cases, at all) once they begin taking lithium again. These observations are supported by small case series, and appear to occur in approximately 10 to 15% of patients who stop taking lithium. Slowly tapering off lithium treatment did not seem to influence whether or not patients would re-respond to lithium later, while there was some indication that more time off lithium could lower the likelihood of a good re-response.
Earlier data from researcher Trisha Suppes suggested that slowly tapering off lithium treatment (over about two weeks) is superior to tapering rapidly (over a few days), and a slow taper reduced the rate of relapse. Kupka added that he would taper lithium even more slowly (over a period of one to two months) so that early signs of relapse could more readily be observed.
Optimum Lithium Levels
At the 2019 meeting of the International Society for Bipolar Disorders, researcher Willem Nolen discussed optimal lithium levels to prevent episodes of bipolar disorder. Based on the limited number of controlled trials that have examined this issue and a survey of experts in the field, Nolen concluded that the standard dosing target to prevent bipolar episodes would be a blood concentration of 0.6 to 0.8 mEq/liter. This concentration could be dropped to 0.4 to 0.6 mEq/liter for patients who responded well to a higher dosage but needed to reduce side effects, and the concentration could be increased to 0.8 to 1.0 mEq/liter for patients who tolerated lithium treatment but showed an inadequate response.
There was no consensus as to optimal blood concentrations of lithium to prevent bipolar episodes in children and adolescents, but some researchers endorsed the same standard recommended for adults. For elderly patients, the majority of researchers recommended a slightly lower concentration of 0.4 to 0.6 mEq/liter, with the option to increase to a maximum of 0.8 mEq/liter in those under age 80 and 0.7 mEq/liter in those over age 80.
Lithium Reverses Some White Matter Abnormalities in Youth with Bipolar Disorder
Multiple groups of researchers have reported the presence of white matter tract abnormalities in patients with bipolar disorder. Some of these abnormalities correlate with the degree of cognitive dysfunction in these patients. These white matter tract abnormalities, which are measured with diffusion tensor imaging (DTI), are widespread and can appear as early as childhood in people with bipolar disorder. Researcher Vivian Kafantaris mentioned at the 2019 meeting of the International Society for Bipolar Disorders that lithium treatment in children and adolescents normalizes these alterations, as described in an article she and her colleagues published in the journal Bipolar Disorders in 2017.
Editor’s Note: This is another reason to consider the use of lithium in children with bipolar disorder. Lithium treatment may help normalize some of the earliest signs of neuropathology in the illness.
