A 2014 study by Joseph M. Cerimele and colleagues in the journal Psychiatric Services found that primary care patients with bipolar disorder had severe depression and anxiety, symptoms of other psychiatric illnesses, and psychosocial problems such as housing difficulties, homelessness, or lack of support. Only 26% were referred to specialty mental health care despite the severity of these problems. These findings suggest the primary care setting, where many patients obtain their care, provides insufficient support for people with bipolar disorder.
Editor’s Note: There are several way to overcome the deficient recognition and treatment of bipolar disorder in primary care:
Record mood fluctuations
It is critical that patients keep a detailed longitudinal record of mood fluctuations in order to enhance the likelihood that their doctor can perform a well-informed evaluation and assessment of the effects of treatment. Several ways of doing this are available. We offer a variety of printable daily mood charts available on our website. Another option is What’s My M3, a free app that can be downloaded from the Itunes Store or Google Play. In a three-minute survey, it screens for depression, anxiety, OCD, PTSD, and mania. The ratings can be done longitudinally and printed out to assist a physician in the evaluation, assessment of course of symptoms, and response to treatment.
Parents of children aged 2–12 with mood or behavioral problems (or at risk for them because they have a parent with a diagnosis of depression or bipolar disorder) can rate their children each week as part of a new study. These ratings, which will help determine how children with symptoms of mental illness are being treated in the community, are done via a secure website and can be printed out to help a treating physician or other clinician to evaluate the children’s course of illness and responses to treatments. Access to informed consent documents and more information about participation in the study, known as the Child Network, is available here.
Learn about mood disorders
Patients should educate themselves about the signs and symptoms of mood disorders. Many books on this topic are available, and the BNN newsletter tries to update patients and clinicians about the latest findings about the treatment of depression and bipolar disorder.
Get extra help
Patients can seek out consultations with experts in bipolar disorder, who may be able to provide extra guidance to help primary care physicians arrive at the appropriate diagnosis or find an optimal treatment plan and back up approaches if the initial options do not bring about remission.
Finding a psychotherapist who can provide psychoeducation about bipolar disorder and cognitive behavioral or other specialized therapies may also be of great use, as more than a dozen randomized studies document the effectiveness of psychoeducation and/or psychotherapy compared to treatment as usual.
Talk about mood at every medical evaluation
Many medical problems such as heart disease and diabetes require careful monitoring, with patients as active participants. Likewise, careful monitoring of mood is a critical component of good treatment and should yield positive short-term and long-term results in recurrent depression and bipolar disorder.
Since depression can complicate many medical illnesses, patients should get in the habit of asking physicians not only about their blood sugar, blood pressure, or cholesterol, but also, “What about my low mood, anxiety, or insomnia?” It may be just the spark a physician needs to better attend to these equally important health issues.
Relatively little attention has been paid to the children of a parent with bipolar disorder, who are at risk not only for the onset of bipolar disorder, but also anxiety, depression, and multiple other disorders. These children deserve a special focus, as on average 74.2% will receive a major (Axis 1) psychiatric diagnosis within seven years.
New research published by David Axelson and colleagues in the American Journal of Psychiatry describes a longitudinal study comparing children who have a parent with bipolar disorder to demographically matched children in the general public. Offspring at high risk for bipolar disorder because they have a parent with the disorder had significantly higher rates of subthreshold mania or hypomania (13.3% versus 1.2%) or what is known as bipolar disorder not otherwise specified (BP-NOS); manic, mixed, or hypomanic episodes (9.2% versus 0.8%); major depressive episodes (32.0% versus 14.9%); and anxiety disorders (39.9% versus 21.8%) than offspring of parents without bipolar disorder. Subthreshold episodes of mania or hypomania (those that resemble but do not meet the full requirements for bipolar disorder in terms of duration) were the best predictor of later manic episodes. This finding was observed prospectively, meaning that patients who were diagnosed with manic episodes during a follow-up assessment were likely to have been diagnosed with a subthreshold manic or hypomanic episode during a previous assessment.
The study included 391 children (aged 6–18) of at least one bipolar parent, and compared these to 248 children of parents without bipolar disorder in the community. The participants took part in follow-up assessments every 2.5 years on average, for a total of about 6.8 years. Each follow-up assessment included retrospective analysis of symptoms that had occurred since the previous assessment.
In addition to having more subthreshold manic or hypomanic episodes; manic, mixed, or hypomanic episodes; and major depressive episodes, the high-risk children also showed more non-mood-related axis 1 disorders, including attention deficit hyperactivity disorder (ADHD), disruptive behavior disorders, and anxiety disorders than the children of parents without bipolar disorder. Axelson suggested that monitoring for these symptoms may help with early identification and treatment.
Children with a bipolar parent were diagnosed with bipolar spectrum disorders at rates of 23% compared to 3.2% in the comparison offspring. Mean age of onset of mania or hypomania in the high-risk offspring was 13.4 years. Of those offspring who had a manic episode, more than half had the episode before age 12, with the earliest occurring at age 8.1.
Compared to previous studies of children of parents with bipolar disorder, this study found that the mean age of onset of manic or hypomanic episodes was younger, possibly because other studies did not include young children. Another new finding was that major depressive episodes were risk factors for mania and hypomania but did not always precede the onset of mania or hypomania in the high-risk offspring.
Parents of children who are at high risk for developing bipolar spectrum disorders should be aware of the common precursors to mania—subthreshold manic or hypomanic symptoms and non-mood disorders—and make sure that clinicians assess for these symptoms and differentiate them from the symptoms of depression or other disorders.
Editor’s Note: In Axelson’s study, 74.2% of the offspring of a bipolar parent suffered a major (Axis I) psychiatric disorder. However, 48.4% of the offspring from the comparison group of community controls also had an Axis 1 psychiatric disorder. These high rates of illness and dysfunction indicate the importance of monitoring a variety of symptom areas and getting appropriate evaluation and treatment in the face of symptoms that are associated with impairment in both high risk children and in the general population.
One way of doing this is for parents to join our new Child Network, a study collecting information about how children at risk for bipolar disorder or with symptoms of bipolar disorder are being treated in the community and how well they are doing. Parents rate their children on a weekly basis for depression, anxiety, ADHD, oppositionality, and mania-like symptoms. Parents will be able to produce a longitudinal chart of their children’s symptoms and response to treatment, which may assist their child’s physician with early detection of illness and with treatment. See here for more information and to access informed consent documents.
The timeframe during which recovery and recurrence occur in people with a first episode of mania are somewhat variable. A meta-analysis by Andréanne Gignac and colleagues published in the Journal of Clinical Psychiatry in 2015 offers some new information. The meta-analysis included eight studies with a total of 734 participants in a first episode of mania. Syndromal recovery rates (when patients no longer met diagnostic criteria for bipolar disorder) were 77.4% at six months after first episode of mania and 84.2% at one year after. However, some symptoms lingered, and only 62.1% of patients reached a period of symptomatic recovery within one year.
Recurrence rates were 25.7% within six months, 41.0% within one year, and 59.7% by four years. Those who were younger at the time of the first episode were at higher risk for relapse within one year.
Editor’s Note: On the positive side, most recovered, but on the negative side, at one year, 60% remained symptomatic and 40% had a recurrence. What is not clear is how intensively patients were treated and monitored. The main message of this study is that a first episode of mania is not trivial and deservces concerted acute and long-term treatment. When expert multimodal treatment is given results are vastly more superior than treatment as usual (Kessing et al. British Journal of Psychiatry 2013).
Ketamine, an anesthetic sometimes used intravenously in the treatment of depression, can bring about rapid onset of antidepressant effects. A new meta-analysis by researcher Michael Bloch and colleagues presented at a recent conference showed that ketamine’s maximum antidepressant effects occur within one day of administration, and its effects remain significant (compared to control conditions) one week following infusion. Ketamine’s effects were diminished in patients taking other medications. There was a trend for better response in patients with bipolar disorder than with unipolar disorder.
Bloch and colleagues analyzed eight earlier studies including a total of 180 participants. In each study, ketamine had been compared to a control condition, either an infusion of saline solution or of midazolam, which mimics ketamine’s sensory effects but does not have antidepressant effects. The researchers are calling for more meta-analyses of ketamine studies to determine which patients respond best to ketamine and how to sustain ketamine’s effects.
Editor’s Note: In another poster presented at the same conference, James Murrough reported that patients with slower processing speed responded best to ketamine. Other findings have shown that those with a history of alcohol abuse and a common genetic variant of brain-derived neurotrophic factor (BDNF), the val-66-val allele of proBDNF, are more likely to respond to ketamine.
Several genes have previously been implicated in bipolar illness. In a recent study, researchers at the Mayo Clinic, led by Paul Croarkin, compared variations in three genes (CACNA1C, ANK3, and ODZN) across 69 children aged 6–15 with mania, a 776-person control group from the Mayo Biobank database, and 732 adults with bipolar disorder (some with onset in childhood and adolescence and some with onset in adulthood, also from the Biobank). All participants were Caucasian, to minimize confounding by population stratification. The researchers found that the minor allele of rs10848632 in CACNA1C was associated with childhood onset of bipolar disorder. The haplotype (or sequence of nucleotides) T-G-G-T was the one associated with risk. Genetic risk scores were also associated with early onset of illness.
Editor’s Note: In research by Michael McCarthy and colleagues, CACNA1C has been linked to abnormal circadian rhythms in bipolar disorder and to responsiveness to lithium treatment. Together, these data suggest the importance of studying the calcium channel blocker nimodipine (which blocks calcium influx through CACNA1C) in childhood-onset bipolar disorder. A 1999 case report by Pablo A. Davanzo and colleagues described a teenager with ultra rapid cycling bipolar disorder (multiple mood switches/day) that did not respond to a host of conventional medications, who improved dramatically on nimodipine, reaching remission. This author (Robert M. Post) has also seen confirmed responsivity in adults with rapid cycling bipolar disorder (reported in the 2008 book Treatment of Bipolar Illness: A Casebook for Clinicians and Patients, by Post and Gabriele S. Leverich).
Children who have a parent with bipolar disorder are at risk for bipolar illness, but it may first present as depression. Treating these children with antidepressants has the risk of bringing on manic episodes. Researchers are looking for treatment options for youth at risk for bipolar disorder.
Robert McNamara and colleagues found that 12 weeks of omega-3 fatty acids (2,100 mg/day) significantly improved response rates in medication-free youth ages 9–20 years compared to placebo (64% versus 36%). Omega-3 fatty acids but not placebo also reduced the activation of limbic structures in the brain (the left parahippocampal gyrus) in response to emotional stimuli.
Editor’s Note: These data add to the literature on the positive effects of 1–2 grams of omega-3 fatty acids in depression. Given the safety of omega-3 fatty acids and the ambiguous effects of antidepressants in bipolar depression, omega-3 fatty acids would appear to a good alternative, especially since the FDA-approved atypical antipsychotics (quetiapine and lurasidone) are not approved for bipolar depression in people under age 18.
Both bipolar disorder and unipolar depression often begin in childhood or adolescence, but it can be difficult to distinguish the two using symptoms only. People with bipolar illness may go a decade without receiving a correct diagnosis. Researcher Jorge Almeida and colleagues recently performed a meta-analysis of previous studies to determine what neural activity is typical of children with bipolar disorder versus children with unipolar depression while processing images of facial emotion. They found that youth with bipolar disorder were more likely to show limbic hyperactivity and cortical hypoactivity during emotional face processing than youth with unipolar depression. Almeida and colleagues hope that this type of data may eventually be used to diagnose these disorders or to measure whether treatment has been successful.
Electroconvulsive therapy is often considered a primary treatment option for patients with severe bipolar disorder that has resisted pharmacological treatment. Researcher Helle K. Schoeyen and colleagues recently published the first randomized controlled trial comparing ECT (in this case right unilateral brief pulse ECT) with algorithm-based pharmacological treatment in 76 patients with treatment-resistant bipolar depression.
The response rate was significantly higher in the ECT group than in the patients who received drug treatment (73.9% versus 35.0%). However, the two treatment groups had similarly low remission rates (34.8% for ECT and 30.0% for pharmacological treatment).
The algorithm-based pharmacological treatment used in the study was based on a sequence of treatments endorsed by researchers Frederick K. Goodwin and Kay Redfield Jamison in their 2007 book Manic-Depressive Illness. A selected treatment was chosen for each participant based on his or her medical history. If the first treatment was ineffective or intolerable, the patient would be switched to the next treatment option. Antipsychotics, antidepressants, anxiety-reducing drugs, and hypnotics were some of the other treatments included in the algorithms.
Patients in the study had previously showed a lack of response to at least two different antidepressants and/or mood stabilizers with documented efficacy in bipolar disorder (lithium, lamotrigine, quetiapine, or olanzapine) in adequate doses for a period of 6 weeks (or until they quit because of side effects).
Editor’s Note: Even when ECT is effective, there is the issue of how to maintain that good response. We previously reported that in a 2013 study by Axel Nordenskjöld et al. in the Journal of ECT, intensive followup treatment with right unilateral brief pulse ECT combined with pharmacotherapy was more effective than pharmacology alone at preventing relapses. Patients who improved after an acute series of ECT (three times/week) then received weekly ECT for six weeks and every two weeks thereafter, totaling 29 ECT treatments in one year.
Other studies of more intermittent continuation ECT have not proved more effective than medication. Thus high intensity right unilateral brief pulse ECT is one option for extending the effects of successful ECT.
“Society’s accumulated myths and fears about disability and disease are as handicapping as the…limitations that flow from actual impairment.”
—US Supreme Court
Attorney Katharine Gordon has provided some information on legal rights under the ADA.
When we think of the Americans with Disabilities Act (ADA), we might think of physical modifications to buildings, expensive lawyers, and complicated trials. But this law also gives people with bipolar ways to get fair treatment in the workplace. By learning a bit about your employment rights under this law, you can focus on excelling in your chosen career, rather than being sidetracked by ignorance, stereotypes, and stigma.
Here are a few things that you may not know about bipolar disorder and the ADA:
It is now clear that people with bipolar disorder are protected under the ADA in employment. Prior to 2008, there was often a battle of the experts to prove that a person with bipolar disorder had a severe enough impairment to be protected. This discouraged many from asking for their rights to be respected under this law in the first place. Unfortunately, companies would fire people for having bipolar disorder and then, in next breath, argue that bipolar wasn’t a real disability therefore it was legal to fire people for reasons related to their bipolar disorder.
This changed with the passage of the Americans with Disabilities Act Amendments Act of 2008, which made it easier to establish disability. The Equal Employment Opportunity Commission, the agency responsible for enforcing this law, has made it clear in official regulations that bipolar should generally be covered as a disability for the purposes of protection in employment: “It should easily be concluded that the following types of impairments will, at a minimum, substantially limit the major life activities indicated:…major depressive disorder, bipolar disorder, post-traumatic stress disorder, obsessive compulsive disorder, and schizophrenia substantially limit brain function.” 29 C.F.R. § 1630.2(j)(3)(ii), (iii).
Job applicants should never be asked whether they have bipolar disorder (or any other disability) until a conditional offer has been made. Read more
In 2012 we reported on an open study by Athanasios Koukopoulos and colleagues that explored whether the NMDA glutamate receptor antagonist memantine (Namenda), which is used to treat dementia, could be helpful to people with treatment-resistant bipolar disorder. In an update of that study, the researchers, led by Giulia Serra, compared patients’ symptoms during three years of treatment as usual, followed by three years with memantine added to their stable medication regime (at doses of 20–30 mg/day). Patients improved progressively over the three years of taking memantine.
Improvements in symptoms included decreased time ill, decreased severity of symptoms, decreased duration of new episodes, and fewer episodes per year. Memantine was particularly helpful for those patients who had had rapid or continuous cycling. Side effects were minimal.
Given the success of this open study, randomized controlled trials are needed to explore this much-needed option for people with treatment-resistant bipolar disorder.