While electroconvulsive therapy (ECT) is very effective treating acute depression, especially among patients who have not responded to antidepressants, relapse rates following ECT are high. Researchers have been exploring treatments that may extend the effectiveness of ECT and reduce relapses, including antidepressant medication and continuation ECT. A new study by Eva-Lotta Brakemeier and colleagues in the journal Biological Psychiatry finds that cognitive-behavioral therapy combined with medication was most effective at sustaining response to ECT.
In the study, 60 patients who responded well to three-times-per-week right unilateral ultra-brief ECT then were prescribed antidepressant medication following current guidelines for ECT followup. Of these patients, one-third were randomly assigned to receive the medications only. Another third were randomly assigned to receive the medications and continuation ECT, and the final third were randomly assigned to receive medication and participate in 15 weeks of cognitive-behavioral therapy in a group setting. Each group was observed at six months, and then at one year. The group who received medication and cognitive behavioral therapy had significantly higher response rates than the other groups at both follow-up evaluations.
After the initial treatment with ECT, 70% of the patients had responded and 47% had achieved remission. Following the six months of continuation treatment, 77% of the group that received medication and cognitive behavioral therapy responded, while only 40% of the group receiving medication and continuation ECT responded, and 44% of those receiving medication alone responded. After one year (six months following the end of treatment), response rates were 65% for those who had received medication and therapy, 28% for those who had received medication and ECT, and 33% for those who had received medication alone.
Editor’s Note: These results are striking for several reasons. As has been found in most studies, continuation ECT is not very effective at sustaining remission. Cognitive behavioral therapy with medication beats the other options hands-down. These results are in accord with others that show that cognitive behavioral therapy also helps prevent relapses in patients who responded well to medications. The take-home message is that people who respond well to antidepressant medication or ECT would do well to add cognitive behavioral therapy to their other preventive treatments.
The current study did not replicate parameters for continuation ECT that were successful in a study by Axel Nordenskjöld and colleagues in the Journal of ECT in 2013. Nordenskjöld used weekly ECT for six weeks and every two weeks thereafter, for a total of 29 ECT treatments in one year, and found this more intense regimen was more effective at preventing relapse than medication alone.
Lithium inhibits the enzyme glycogen synthase kinase 3, which has been implicated in dementia. To study whether lithium may prevent cognitive decline, researchers led by Tobias Gerhard looked at the medication histories of patients with bipolar disorder who were 50 years of age or older. In their article published in the British Journal of Psychiatry, those patients who had taken lithium 301–365 days out of the previous year had substantially lower risk of dementia than those who had not taken lithium during that time. Patients who had 300 or fewer days of lithium use did not have a significant reduction in dementia risk, nor did patients who were prescribed anticonvulsant drugs.
Editor’s Note: These data are consistent with those of Lars Kessing and colleagues, which suggest that patients in Denmark who renewed their lithium prescriptions were less likely to receive a diagnosis of dementia in old age.
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.
Borderline personality disorder is characterized by mood instability, cognitive symptoms, impulsive or risky behavior, and disturbed interpersonal relationships. There are no Federal Drug Administration–approved treatments, but several small open studies of the atypical antipsychotic quetiapine (trade name Seroquel) have been promising. Rapid mood shifts in borderline personality disorder resemble to some extent those in bipolar disorder, for which quetiapine is an approved treatment. The drug may also curb impulsivity and self-harm. A blind, placebo-controlled study by Donald W. Black and colleagues published in the American Journal of Psychiatry in 2014 compared a low dose of quetiapine (150mg/day) with a moderate dose (300mg/day) and with placebo for the treatment of borderline personality disorder. The low dose of quetiapine led to significant improvement over the other doses, particularly reducing verbal and physical aggression.
The study included 95 participants randomized to each of the three treatment groups. All met DSM-IV criteria for borderline personality disorder, and each participant received eight weeks of active treatment. (One week of 50mg/day followed by seven weeks of 150md/day for the low dose group, and one week of 50mg/day followed by 3 weeks of 150mg/day and 4 weeks of 300mg/day for the moderate dose group.)
Eighty-eight percent of the participants experienced an adverse event during the study, including sedation, dry mouth, increased heart rate, or decrease in blood pressure. None were serious. Sedation was most common in the group receiving moderate doses of quetiapine.
All groups improved over the 8-week study, particularly during weeks 2–6. Response rates of participants who completed the study were 82% for the low dose group, 74% for the moderate dose group, and 48% for placebo. (Large benefits from placebo are common in studies of borderline personality.) Improvement in symptoms was greatest in the low dose quetiapine group, significantly higher than the moderate dose quetiapine group. Time to improvement was shorter on quetiapine than on placebo.
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.
Studies in Japan, Austria, and Texas have reported that trace amounts of lithium in drinking water are associated with lower suicide rates. A new study seeks to clarify these findings by removing any statistical factors other than lithium levels that could produce these results.
The study, published in the Journal of Clinical Psychiatry, collected 434 lithium samples in drinking water over three years, and compared these with suicide rates in the population of 274 municipalities of Kyushi Island in Japan.
The researchers, led by Nobuyoshi Ishii, then controlled for size of population, proportion of elderly people, proportion of one-person households, proportion of people with a college education or more, proportion of people engaging in primary industry, overall unemployment rates, annual marriage rates, annual mean temperature, and annual savings in per person in Japan’s popular postal bank. In places with slightly higher trace levels of lithium in drinking water, there was a lower rate of suicides in men. Suicide rates for women and overall were not significantly associated with lithium levels.
Omega-3 fatty acids are found in some green vegetables, vegetable oils, and fatty fish. There is some evidence that omega-3 fatty acid supplements can reduce depression, but researchers are trying to clarify which omega-3s are most helpful, and for whom. A new study in Molecular Psychiatry suggests that depressed people with higher inflammation may respond best to EPA omega-3 fatty acids compared to DHA omega-3 fatty acids or placebo. Researchers led by M.H. Rapaport divided people with major depressive disorder into “high” and “low” inflammation groups based on their levels of the inflammatory markers IL-1ra, IL-6, high-sensitivity C-reactive protein, leptin, and adiponectin. Participants were randomized to receive eight weeks of treatment with EPA omega-3 supplements (1060mg/day), DHA omega-3 supplements (900mg/day), or placebo.
While overall treatment differences among the three groups as a whole were negligible, the high inflammation group improved more on EPA than on placebo or DHA, and more on placebo than on DHA. The authors suggest that EPA supplementation may help relieve symptoms of depression in people whose depression is associated with high inflammation levels, a link common among obese people with depression.
Editor’s Note: These data add to a study by Rudolph Uher et al. in which people with high levels of C-reactive protein responded better to the tricyclic antidepressant nortriptylene, while those with low levels of the inflammatory marker responded better to the selective serotonin reuptake inhibitor antidepressant escitalopram.
A new study finds that omega-3 fatty acid supplementation improves attention in boys both with and without attention deficit hyperactivity disorder (ADHD). The study by Dienke J. Bos and colleagues in the journal Neuropsychopharmacology included 40 boys (aged 8–14) with ADHD and 39 demographically matched controls. Participants were given 10 g per day of margarine supplemented with either omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) or placebo.
The children who received EPA/DHA supplementation showed improvements in attention (as rated by parents) compared to those who received placebo. Improvement was greater in the children with ADHD. Supplementation did not affect cognitive control or brain activity on functional magnetic resonance imaging (fMRI). Those boys who received omega-3s showed higher DHA levels on followup.
A new study from Finland suggests that low vitamin D levels in childhood and adolescence can predict atherosclerosis, or hardening of the arteries, in adulthood. The study, by Markus Juonala and colleagues in the Journal of Clinical Endocrinology & Metabolism, included 2,148 people whose vitamin D levels were measured at ages 3–18. They were checked for atherosclerosis at ages 30–45. Those participants with the lowest levels of vitamin D in their youth were at much higher risk for thickened arteries as adults. The finding was independent of other cardiovascular risk factors such as smoking, high blood pressure, poor eating, lack of exercise, and obesity.
Editor’s Note: While it is not yet clear if low vitamin D levels directly cause the development of atherosclerosis, it is important to maintain sufficient vitamin D in childhood for a host of reasons, including strong bones. Children with sufficient vitamin D levels are more likely to have normal moods and behavior than those deficient in vitamin D.
New research shows that expressions of maternal warmth following corporal punishment do not reduce children’s anxiety, and may even increase it.
The study by Jennifer E. Lansford and colleagues was published in the Journal of Clinical Child & Adolescent Psychiatry. The researchers interviewed over a thousand children aged 7–10 and their mothers about what type of physical punishment occurs in their family, and about anxiety and aggression in the children. They followed up again after one and two years. The study took place in eight countries: China, Colombia, Italy, Jordan, Kenya, the Philippines, Thailand, and the United States.
In general, corporal punishment increased anxiety in the children, while maternal warmth decreased it. How warmth and physical punishment interacted depended on the country. Anxiety increased over time in families where the mothers were high on both corporal punishment and warmth. Lansford and colleagues wrote that it might be “simply too confusing and unnerving for a child to be hit hard and loved warmly all in the same home.”
The researchers suggest that parents use nonphysical ways to promote desirable behavior in their children, including putting younger children in time-out and requiring teenagers to participate in activities that help others.