Keith O’Neil is a former Super Bowl champion and the founder of the Forever Foundation, an organization whose mission is to educate the public about bipolar disorder and to de-stigmatize the illness. In September he spoke at the Brain and Behavior Research Foundation (formerly NARSAD) meeting in Washington, DC.
O’Neil’s life story holds many important lessons— not only about the difficulties of bipolar illness, but also about the hope of recovery. He described being six years old and experiencing high levels of anxiety and fear, and an inability to get to sleep. His mind raced and he was so irritable that he was nicknamed “The Bear.”
The anxiety and the racing thoughts continued, and O’Neil became increasingly depressed. When he was 10 or 12 years old, he began to experience suicidal thoughts and searched his parents’ medicine cabinet for pills he could use to commit suicide. Anxiety and depression became more prominent even though he was an “A” student, one of the most popular kids at school, and an extraordinary athlete, and had a loving family and many friends. He began to use alcohol excessively, had conduct problems, was impulsive and was always in trouble.
O’Neil excelled in football in high school, started college at Northern Arizona University, and quickly became an All-American linebacker at Penn State. He was a first-round draft pick for the New York Giants. His teammates would nap between workouts for coach Bill Parcells, but instead, O’Neil would sit and cry over his inability to sleep. When he was later picked up by the Dallas Cowboys as a free agent, he was unable to sleep for five nights.
O’Neil moved on to the Indianapolis Colts. He did not sleep for four nights before his first game, and told coach Tony Dungy that he needed help, as he did not think he could play the next day. Dungy took him seriously and had him meet with the general manager, the team doctor, and the trainer. O’Neil felt extraordinarily relieved to be able to talk about his anxiety for the first time and took some clonazepam (Klonopin) for sleep and anxiety. Although he missed his first game, he became increasingly successful and the captain of the team that three years later would go on to win the Super Bowl.
O’Neil returned to the Giants for five seasons. While in New York, his wife miscarried, triggering O’Neil’s first major manic episode. He felt super human, spent excessive amounts of money (bought a Rolex watch and three diamond earrings), did not need sleep, and was generally out of control. In 2010, O’Neil was diagnosed with bipolar disorder by Steven Dubovsky, one of the pioneers in the development of calcium channel blockers for the treatment of bipolar disorder.
After his manic episode, O’Neil swung into a severe 18 month–long depression, which he described as “the depths of hell.” He gradually improved and started on a regimen that included medications, exercise, and relying on his family for comfort and support. He then moved to Phoenix, Arizona to start his foundation—the Forever Foundation.
The foundation provides information about the illness and promotes de-stigmatization. O’Neil visits high schools to teach students about bipolar illness and the importance of talking about anxiety and depression and getting help.
In the question and answer period following his talk, O’Neil discussed his own treatment. His early experiences with antidepressants were somewhat positive for his depression and anxiety, but may have been influential in his first manic episode. He said he is now well, and described his current medication regimen, which includes lithium, the mood stabilizing anticonvulsant oxcarbazepine (called Trileptal, which is structurally similar to carbamazepine or Tegretol), and the atypical antipsychotic aripiprazole (Abilify), which works extraordinarily well for him and which he called his savior. O’Neil occasionally uses Ambien (zolpidem) or Seroquel (quetiapine) for sleep.
O’Neil talked about the importance of confronting his own illness and adopting a positive attitude about getting treatment and doing everything he could to get well. He had a family history of mood disorders including depression in his paternal grandfather and bipolar disorder in an uncle.
O’Neil remembered that in his days as a professional football player, even though he was a standout player, he was so anxious that he would get confused about the playbook and have to rehearse it over and over in order to remember. He felt that he dealt with his racing mind and his anxiety in part by funneling it into “controlled recklessness” as a football player.
Keith O’Neil received a standing ovation from the gathering of scientists and approximately 150 supporters of the Brain and Behavior Research Foundation .
It is noteworthy that after Keith’s presentation, many of the scientific presenters speaking about the latest advances in the understanding and treatment of anxiety disorders in children, depression, and bipolar disorder directly referred to his life story and the important messages embedded in it. Read more
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, there was an excellent symposium on different psychotherapeutic approaches for children and adolescents with bipolar disorder and related illnesses.
Amy West of the university of Illinois at Chicago started off this symposium by describing the effectiveness of child-and family-focused cognitive-behavior therapy or what is sometimes called RAINBOW therapy. Rainbow stands for Routine, Affect regulation, I can do it, No negative thinking, Be a good friend and balance life stressors, Oh how can we solve problems, and Ways to find support.
West emphasized the importance of routine in sleep, diet, medications, and homework, and indicated that frequent soothing is necessary. Posted reminders are also helpful.
Affect regulation can be encouraged by promoting coping skills, particularly around identifying what triggers mood swings and rage attacks and creating plans for dealing with them.
“I can do it” reminds parents and children to focus on strengths, successes, positive feedback, and the ability to call for help.
“No negative thinking” encourages positive restructuring and reframing of negative perspectives. Part of this includes mindfulness training for children and parents, who are taught to focus on breathing and accepting thoughts and emotions.
Being a good friend focuses on listening, engaging friends, and enhancing communication.
“Oh how can we solve problems” reminds families to have an attitude of problem solving.
Remembering ways to find support reminds parents to connect with relevant resources, and also coaches parents to be advocates for their children.
In a randomized study of 12 sessions of child and family focused cognitive behavior therapy, the children did much better than those receiving treatment as usual and showed greater improvement in mania and depression as well as overall functioning.
The second presentation was given by Mary Fristad of Ohio State University. She treated children with bipolar disorder not otherwise specified (BP-NOS) with psychotherapy and omega-3 fatty acids. Some research had suggested the efficacy of omega-3 fatty acids in childhood mood disorders and a much larger literature was positive in adult mood disorders. Given the safety of the manipulation, she felt it was worth trying in young children and those with BP-NOS who are rarely studied formally. She also cited a 2010 study by Amminger et al. in children who were at ultra high risk for schizophrenia. In that study, patients were randomized to 12 weeks of omega-3 fatty acids or placebo, and omega-3 fatty acids were associated with a very low conversion rate to full-blown psychosis, 4.9%, compared to 27.5% for those receiving placebo. Fristad’s psychotherapy also emphasized education, support, and skill building in order to enhance understanding of the illness and its treatment. This would help ensure better compliance and better treatment outcome. Her formal treatment manual is available at www.moodychildtherapy.com.
Fristad randomized children with bipolar not otherwise specified, average age 10.2 +/- 0.2 years to either her psychotherapy plus omega-3 fatty acids or therapy plus placebo. Therapy plus omega-3 was much more effective on most outcome measures.
Editor’s Note: Given the safety of omega-3 fatty acids, even these limited data would appear to justify their use in children with BP-NOS in the context of psychotherapy and psychoeducation.
The third presenter was David Miklowitz of UCLA who discussed family focused therapy. This approach has proven effective in studies of both adults and adolescents with bipolar disorder, and as well for those with prodromal symptoms. Read more
Researcher Ben Goldstein reported at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry that children with bipolar disorder have levels of inflammatory markers in the same range as people with inflammatory illnesses, such as rheumatoid arthritis. In his research, increases in the inflammatory marker c-reactive protein (CRP) occurred in proportion to the severity of manic symptoms in the children.
Goldstein also discussed cognitive dysfunction, which is often seen early in the course of childhood onset bipolar disorder. Goldstein described studies showing that this type of cognitive dysfunction consists of a decrease in reversal learning, a measure of cognitive flexibility. Elevated CRP was significantly associated with deficits in a child’s composite score for reversal learning.
Together these data suggest that inflammation could play a role in disease disability and cognitive dysfunction in childhood bipolar disorder.
There is a large body of research showing that lithium is better than placebo and a variety of comparison drugs at preventing manic episodes in people with bipolar disorder. It has been less clear whether lithium is as effective in preventing depressions in bipolar patients. In a 2014 meta-analysis in the International Journal of Bipolar Disorders, Emanuel Severus and colleagues confirmed that lithium was more effective than placebo at preventing mood episodes overall and manic episodes. In a fixed effect statistical analysis, lithium was also better at preventing depressive episodes.
The portion of the meta-analysis comparing lithium to placebo included seven randomized controlled trials that included a total of 1,580 patients. Lithium was more likely than placebo to lead to patients dropping out of a study for reasons other than a mood episode, but patients who received lithium were more likely to complete their clinical trials.
Another part of the meta-analysis compared lithium to anticonvulsant drugs. Seven trials were included totaling 1,305 patients. Lithium was better than anticonvulsants at preventing manic episodes, but equally effective at preventing mood episodes overall and depressive episodes specifically. There was also no difference in patients dropping out of the trials or completing the trials.
The researchers concluded that lithium remains the most valuable treatment option for bipolar disorder, because no other drug has such consistent efficacy in preventing manias and depressions and mood episodes in general.
A recent twin study suggests that the genes that confer risk for bipolar disorder may also be associated with verbal ability and sociability. Considerable evidence has suggested that people with bipolar disorder have greater intelligence and creativity than the normal population. Positive qualities like these may make people with bipolar disorder attractive mates, leading to the continued propagation of genes that promote bipolar disorder. (One might expect lower than normal rates of reproduction in people with bipolar disorder due to the difficulties the illness creates, as occurs with schizophrenia, but people with bipolar disorder have normal rates of reproduction, suggesting that any obstacles to mating are balanced by other particularly attractive qualities.)
Researchers led by Rachel G. Higier used a Swedish registry of twins to investigate whether people with bipolar disorder and their fraternal or identical twins without the illness have better verbal ability and sociability. Bipolar patients and their twins (who would be expected to have similar genetic and familial risks but without the negative impact of the illness and medications for it) were compared to patients with schizophrenia and their twins and normal controls. The well twins of bipolar patients scored higher on a scale of positive temperament than the bipolar patients, schizophrenia patients and their twins, and controls. The twins of bipolar patients also scored better than schizophrenia patients and their twins and controls on tests of verbal learning and fluency, while the bipolar patients showed lower levels of cognitive function (likely due to their illness).
The researchers conclude that the genes that put families at risk for bipolar disorder also confer positive traits like verbal ability and positive temperament that make people with bipolar disorder attractive mates. Even though bipolar disorder may reduce these traits somewhat, people with the illness still are more creative than the general population and often very successful.
In a poster at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Larissa Portnoff reported that NF-kB, a marker of inflammation that can be measured in two types of white blood cells (lymphocytes and monocytes), was significantly elevated in adolescents who had bipolar disorder compared to healthy control participants.
Several other inflammatory markers have been linked to bipolar disorder, including c-reactive protein (CRP) and TNF alpha. The new data about NF-kB suggests that another inflammatory pathway is overactive in the disorder. NF-kB levels did not correlate with the severity of manic or depressive symptoms, as do levels of some other inflammatory markers.
At the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Robert Findling reported on a double blind, placebo controlled 36-week study of lamotrigine for children and adolescents with bipolar I disorder. The doses designed for maintenance treatment averaged about 225 mg/day, achieved by very slow increases over time in order to reduce the risk of a serious rash.
Findling found that lamotrigine was more effective than placebo in extending the time until a patient required an intervention for a new mood episode among the older children in the study (aged 13 to 17). Among the younger children in the study (aged 10 to 12), lamotrigine’s effects were not statistically significant compared to placebo. Findling and colleagues concluded that lamotrigine appeared effective in delaying time to onset of a new episode in adolescents with bipolar I disorder.
Lamotrigine is approved by the Federal Drug Administration (FDA) for bipolar disorder in adults only.
In a huge study of Swedish siblings, a sibling was 24.7 times more likely to have bipolar disorder if the father was older (over age 45) at the time of the birth than younger (younger than 24). Older paternal age was also associated with other risks of mental disorders, such as autism, attention deficit hyperactivity disorder (ADHD), suicide attempts, substance abuse and psychosis, but the strongest finding was of a relationship with bipolar disorder.
Mutations that occur during the production of sperm may be responsible for the increased risk of illness in the offspring of older fathers.
The population-based cohort study published by Brian M. D’Onofrio et al. in the journal JAMA Psychiatry included all individuals born in Sweden between 1973 and 2001.
Three articles in the September 2014 issue of the journal Psychiatric Annals (Volume 44 Issue 9) discussed differentiating pediatric bipolar disorder from attention deficit hyperactivity disorder (ADHD). The first article, by Regina Sala et al., said that reasons to suspect bipolar disorder in a child with ADHD include:
- The ADHD symptoms appear for the first time after age 12.
- The ADHD symptoms appear abruptly in an otherwise healthy child.
- The ADHD symptoms initially responded to stimulnts and then did not.
- The ADHD symptoms come and go and occur with mood changes.
- A child with ADHD begins to have periods of exaggerated elation, grandiosity, depression, decreased need for sleep, or inappropriate sexual behaviors.
- A child with ADHD has recurring severe mood swings, temper outbursts, or rages.
- A child with ADHD has hallucinations or delusions.
- A child with ADHD has a strong family history of bipolar disorder in his or her family, particularly if the child does not respond to appropriate ADHD treatments.
The second article, by this editor Robert Post, Robert Findling, and David Luckenbaugh, emphasized the greater severity and number of symptoms in childhood onset bipolar disorder versus ADHD. Children who would later develop bipolar disorder had brief and extended periods of mood elevation and decreased sleep in the early years of their lives. These, along with pressured speech, racing thoughts, bizarre behavior, and grandiose or delusional symptoms emerged differentially from age three onward. In contrast, the typical symptoms of ADHD such as hyperactivity, impulsivity, and decreased attention were equal in both diagnoses.
In the third article, Mai Uchida et al. emphasized the utility of a family history of bipolar disorder as a risk factor. Moreover, a child with depression plus ADHD is at increased risk for a switch into mania on antidepressants if there is a family history of mood disorders, emotional and behavioral dysregulation, subthreshold mania symptoms, or psychosis.
The differential diagnosis of ADHD versus bipolar disorder (with or without comorbid ADHD) is critical, as drug treatment of these disorders is completely different.
Bipolar disorder is treated with atypical antipyschotics; anticonvulsant mood stabilizers, such as valproate, carbamazepine, or lamotrigine; and lithium. Only once mood is stabilized should small doses of stimulants be added to treat residual ADHD symptoms.
ADHD, conversely, is treated with short- or long-acting stimulants such as amphetamine or methylphenidate from the onset, and these may be augmented by the noradrenergic alpha-2 agonists guanfacine or clonidine. The selective noradrenergic re-uptake inhibitor atomoxetine is also approved by the Federal Drug Administration (FDA) for the treatment of ADHD. The dopamine-active drug bupropion and the anti-narcolepsy drugs modafinil and armodafinil have mild anti-ADHD effects but have not been FDA-approved for that purpose.
In the clinic of researcher Eduard Vieta in Barcelona, a study was recently completed showing that antidepressant use in patients with bipolar disorder (where antidepressants are not effective) had dropped from around 50-60% in 2007 (in Baldessarini’s study) to about 30% in 2013 and 2014, and conversely lithium, anticonvulsants, and atypical antipsychotics, which have much more evidence of efficacy, were all used much more often, or about 60% of the time.
Editor’s Note: Hopefully these data from Spain will soon be matched by similar data in the US showing that evidenced-based treatments for bipolar depression are in fact being used instead of antidepressants, which can have adverse effects, such as switching into mania or cycle acceleration.