Risks and Difficulties of Treating Childhood-Onset Bipolar Disorder

boy with psychiatristEarly treatment is needed in childhood onset bipolar disorder

Multiple factors make childhood-onset bipolar disorder a difficult problem for affected children and families. Early onset is common, and treatment is often delayed or inappropriate.  It takes an average of nine months to achieve remission, and relapses are common. In studies children have remained symptomatic for an average of two-thirds of the time they receive naturalistic follow up treatment, and the illness impairs social and educational development. Episodes and stressors tend to accumulate, and substance abuse is a frequent complication. Dysfunction and disability occur at a high rate among children with the illness, and suicidal ideation and acts are common.

When we surveyed adults in our treatment network, the Bipolar Collaborative Network (BCN), about the history of their illness, we found that the duration of the time lag between illness onset and first treatment was independently related to a poor outcome in adulthood.  A longer delay to first treatment was associated in adulthood with greater depression severity, more days depressed, fewer days euthymic, more episodes, and more ultradian cycling (or cycling within a single day). Because treatment delay is a risk factor that can be avoided or prevented, efforts should be made to initiate treatment early in the course of bipolar illness.

More risk and illness adversity factors are present in the US than in Europe

Illness vulnerability factors and a difficult illness course may be more common in the US. There were more familial/genetic risk factors (higher incidence of positive parental history of bipolar illness) among patients at our US sites compared with our sites in the Netherlands and Germany.  There was also more evidence of assortative mating in the US, by which we mean that it was more likely that both parents of a patient had an affective disorder.

There was also more psychosocial adversity among patients at the US sites than in the sites in Germany and the Netherlands, including abuse in childhood, but also including more stressors at the time of illness onset and more stressors immediately prior to the patient’s most recent episode.  These stressors included loss of social support, financial and employment difficulties, and difficulties with health and health-care access. Both familial risk factors and psychosocial stressors in childhood, at illness onset, and prior to the latest episode were more common in the US sites than in the European ones.

In addition, those patients at our sites in the US had an earlier age of illness onset, more episodes, more rapid cycling in the year prior to admission to the treatment network, and a greater incidence of comorbid anxiety and substance abuse disorders. After entering the network, those in the US had a higher incidence of non-response to long-term naturalistic treatment compared with those in Europe.

It was noteworthy that lithium was used more often at the European sites than at the US sites, and with a higher success rate.  In Barbara Geller’s eight-year follow-up of childhood-onset bipolar illness treated in the community, with participants averaging 11 years of age, she not only found a high degree of persistent symptomatic illness, but she also found that 37% of the children never received treatment with lithium, mood-stabilizing anticonvulsants, or an atypical antipsychotic (i.e., the treatments recommended by consensus guidelines). Those children who did receive lithium had the highest rate of remission. More effective treatment in the community may be able to prevent some of the long-term difficulties that patients with bipolar disorder experience in adulthood.

New approaches to generating treatment information

Part of the difficulty in treating childhood onset illness is that there continues to be a lack of systematic treatment literature other than the FDA approval of some atypical antipsychotics for acute mania in children 10 to 17 years of age.  This editor has suggested one potential solution to this dilemma – creating treatment outcome networks for the entire range of externalizing and bipolar spectrum disorders. Information from clinical practice settings could be used to systematically assess what treatments are currently being used and their effectiveness and tolerability.

This kind of clinical network could be complemented by treatment networks in academic centers where potential findings could be explored in comparative clinical trials of treatment agents and combinations of treatments.  An important aspect of these designs would be to switch non-responders to other treatment options so that clinicians could begin to pinpoint optimal initial treatment sequences and best alternatives if these fail to be effective. This is not done in industry-sponsored trials for the FDA, so this critical information is generally lacking.

Eventually it may be possible to link treatment response to clinical and neurobiological markers so that doctors can better predict to which treatments a given patient is most likely to respond.

Finally, it would be important to initiate treatment studies in children at high and ultra-high risk for eventual onset of bipolar disorder since a substantial proportion of children in these categories will go on to develop an affective illness. Children are at high risk if both parents have a unipolar or bipolar affective disorder, and we would consider children at ultra-high risk if: a) both parents have an affective disorder; b) one or both parents are actively ill; and c) the child is already experiencing early or prodromal symptoms.

In these latter instances of ultra-high risk, possible approaches to these children could include: a) close observation; b) family education about the illness and psychopharmacological treatments; c) cognitive behavior therapy and the teaching of coping strategies; d) longitudinal mood-charting; e) facial emotion recognition training, since these emotion recognition skills are often impaired in children with affective disorders; and f) family therapy for enhancing communication and interacting skills.

Given what we already know about the risks of illness and its comorbidities, other practical approaches to children at ultra-high risk could include promoting exercise and ensuring they have a healthy diet that limits omega-6 fatty acids (with their likelihood of driving weight gain and inflammation) and includes vitamin supplements with folate, vitamin D, and omega-3 fatty acids (which are anti-inflammatory). Omega-3 fatty acids have been shown to prevent the conversion of early signs of schizophrenia (called the prodrome) to full-blown schizophrenia, but such a study has not been undertaken in those at high risk for mood disorders.  However, omega-3 fatty acids are promising and should be studied for this purpose because they are safe and multiple positive studies have shown them to be effective in depressive disorders.

It is not just the child who requires support and psychoeducation. Childcare and wellness classes for the family along with family psycho-education about coping skills, social skills, and emotion recognition training could also be helpful. Families with a high level of stress could benefit from volunteer sponsors or a visiting nurse.

All investigators in the field agree that there is an urgent need for more treatment research in childhood-onset bipolar disorder and in those at high risk. It is only with an entire new range of treatment research initiatives that we will be able to intervene optimally in childhood-onset bipolar illness and perhaps transform it into a more benign disorder.

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