NeuroStar TMS Therapy Approved by FDA for MDD

The NeuroStar Transcranial Magnetic Stimulation (TMS) Therapy system was approved by the United States Food and Drug Administration for the treatment of major depressive disorder (MDD). Mark George, MD, of the Medical University of South Carolina (MUSC) initiated research on the treatment.

“I began researching prefrontal TMS as a potential treatment for depression back in 1993, reasoning from the effects of electroconvulsive therapy, emerging brain imaging findings in depression and sadness, and new papers describing corticothalamic regulator loops,” Dr. George said. “The ideas were heretical at first, as most people wrongly assumed that a seizure was needed for an electrical stimulation method to work.”

NeuroStar TMS Therapy is a non-systemic, non-invasive form of neuromodulation that requires no anesthesia or sedation. The 40-minute outpatient procedure involves magnetic resonance imaging-strength magnetic pulses that stimulate nerve cells in areas of the brain associated with depression. These pulses should be administered daily for 4–6 weeks.

The randomized controlled trial conducted for the FDA showed no systemic side effects (eg, sedation, nausea, dry mouth) and no adverse effects on concentration and memory. TMS treatments were safely performed with no seizures and no device-drug interactions. Mild-to-moderate scalp pain at the treatment area was experienced during treatment but dissipated after the first week. This option is for adults with MDD who failed to receive benefit with other treatments. It is not recommended for patients with implanted metallic devices or non-removable metallic objects in or around the head.

Despite over 15 years of research, a rigorous trial sponsored by the National Institute of Mental Health is being conducted at MUSC and three other sites to test the efficacy of prefrontal TMS in depression.

“We have extensive imaging, genetic, demographic, and neuropsychological testing in these patients to help understand the mechanism of action and determine who best responds, and whether biomarkers might help monitor or predict response,” Dr. George said.

The NeuroStar TMS Therapy has not been studied in patients who have received previous antidepressant treatment. Further, efficacy has not been established in patients whose condition did not improve after ≥2 prior antidepressant treatments at minimal effective dose and duration in the current episode.

Funding for this research was provided by the National Alliance for Research on Schizophrenia and Depression. (Further information can be found at http://clinicaltrials.gov/ct2/show/NCT00149838) –ML

Researchers Determine Rates of Child and Adolescent Bipolar I Disorder Becoming Adult Bipolar I Disorder

Current research has found that approximately 1% of the United States population <20 years of age suffers from bipolar disorder. With the onset of bipolar I disorder generally occurring in late adolescence or young adulthood, research is needed to determine whether child bipolar I disorder would become continuous adult bipolar I disorder.

Barbara Geller, MD, and colleagues from the Washington University in St. Louis, Missouri studied 115 children whose average age was 11.1±2.6 years to determine these potential prevalence rates. All of the children met the criteria for a first episode Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar I disorder mixed or manic phase; had one or both of the cardinal symptoms of bipolar I disorder (elation or grandiosity); and scored <60 on the Children’s Global Assessment Scale (CGAS). Geller and colleagues assessed the patients using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, the Psychosocial Schedule for School Age Children-Revised, and the CGAS. 

Over an 8-year period there were nine follow-up visits and approximately 94% of patients completed the study. Geller and colleagues found that these patients spent approximately 60% of weeks with any mood episodes and approximately 40% of weeks with episodes of mania. Approximately 88% of patients recovered from mania; however, approximately 73% of these patients relapsed. Geller and colleagues found that approximately 44% of these children with bipolar I disorder became young adults with bipolar I disorder. These patients continued to have manic episodes while 35.2% had a substance use disorder. This rate is similar to the rate found in adults.

“As we found, these data add to the validation of child bipolar I disorder as a similar illness to the adult form,” Dr. Geller said. “These data are consistent with our earlier publication showing that both child onset and adult onset bipolar I disorder occur within the same families.”

Geller and colleagues plan on following the sample into adulthood. They believe that the rate was similar in young adults because “these prospective longitudinal data and family psychopathology data support that they are the same illness and therefore would have similar comorbidity with substance use disorders. These are the first data to prospectively demonstrate continuity between child and adult bipolar I disorder.”

Funding for this research was provided by the National Institute of Mental Health. (Arch Gen Psychiatry. 2008;65(10):1125-1133.) –CDN

Adolescent Insomnia May Indicate Depression and Substance Abuse in Young Adulthood

Brandy Roane, MS, and Daniel J. Taylor, MD, of the University of North Texas in Denton conducted a study suggesting signs of adolescent insomnia symptoms are linked to depression, suicide, and substance abuse. This study is the first to longitudinally evaluate adolescent insomnia symptoms as a risk factor for mental health problems in young adulthood.

The researchers chose 145 middle, junior, and high schools in the United States based on size, school type, census region, urbanization level, percentage of Caucasian and African-American students, grade span, and curriculum. The sample consisted of 4,494 participants 12–18 years of age at baseline and 3,582 young adults 18–25 years of age at 6- to 7-year follow up. Self-report measures were used to assess mental health conditions. A cross-sectional, prospective design was used to evaluate the association between adolescent insomnia and mental health during adolescence and young adulthood.

Results indicated that 9.4% of adolescents reported insomnia symptoms (ie, difficulty falling asleep every day or almost every day). Cross-sectional analysis showed that these symptoms were associated with use of alcohol (ie, binge drinking; drinking ≥5 alcoholic beverages consecutively), cannabis, and other drugs (eg, cocaine) as well as suicide ideation or attempts. In addition, gender differences emerged for substance abuse and depression. Males were more likely to endorse substance abuse while females were twice as likely to develop depression. Sex and baseline depression were controlled for a prospective analysis that indicated adolescent insomnia symptoms were a significant risk factor for young adult depression (odds ratio=2.3). In addition, when participants suffering from depression and suicide at baseline were excluded, the insomnia cohort showed greater risk of experiencing recurrences of depression and suicidal activities.

These findings indicate that insomnia is a prevalent problem for adolescents. Roane and colleagues argue for future treatment-outcome studies to evaluate the efficacy and effectiveness of various insomnia interventions in this age group. (Sleep. 2008;31(10):1351-1356.) –ML

Children May Present With Course of OCD Similar to Older Peers and Adolescents

Marked by recurrent, unwanted thoughts and/or repetitive behaviors often aimed at relieving these obsessions, obsessive-compulsive disorder (OCD) is not only present in adult populations, but has also been found in children <3 years of age. Prior studies have shown that OCD development in childhood and adolescence features a unique presentation and poses risks to later growth and development.

Despite the differed presentation and risk, there have been few studies into the development of OCD in children. In addition, studies of youths with OCD often do not distinguish between those who present with the disorder as children and patients who develop OCD later in life. Researchers at the Bradley Hasbro Children’s Research Center Pediatric Anxiety Research Clinic in Providence, Rhode Island, recently sought to determine differences in OCD presentation among youths with the disorder.

Abbe M. Garcia, PhD, and colleagues studied 58 children (4–8 years of age; 23 male and 35 female) for distinguishing factors of early-onset OCD presentation. Early-onset OCD was defined as the presence of OCD, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, prior to the 8 years of age, and was determined (along with comorbid conditions) by use of a structured interview. OCD severity was evaluated using the Children’s Yale-Brown Obsessive Compulsive Scale.

Garcia and colleagues found that the mean age of OCD onset was approximately 5 years and the mean age of presentation was 6–7 years. Mean symptom severity was in the moderately severe range while, among all children studied, approximately 19% had been previously treated with medication and 24% had received previous psychotherapy for OCD. Approximately 22% of children in the study also had comorbid attention-deficit/hyperactivity disorder and approximately 20% had comorbid generalized anxiety disorder. In addition, 20% of children in the study reported a first-degree family history of the disorder.

Regarding OCD symptoms of children in the study, common obsessions included contamination and aggressive/catastrophic thoughts, such as death or harm to family members, and common compulsive behaviors included washing and checking. The authors found that children with OCD presented with similar symptoms, severity levels, and family history as adolescents with the disorder, which may indicate that children can progress to the mature OCD course typically found in adults.

Garcia and colleagues concluded that presence of various obsessions and compulsions as well as multiple comorbid conditions indicate that, for some children with OCD, the disorder is not in a beginning phase that will progress as children age. However, they found that children can be affected with similar OCD severity as older children and adolescents. They added that researchers need to have a more developed understanding of the course of OCD in children in order to reduce the severity of symptoms that can impair patients’ quality of life.

Funding for this research was provided by the National Institute of Mental Health. (J Psychopathol Behav Assess. 2008. [Epub ahead of print].) –CP

10-Year Study on Smoking and Depression in Women

A longitudinal study investigated the strength of smoking as a risk factor for major depressive disorder (MDD). One thousand forty-three Australian women, participants in the Geelong Osteoporosis Study, had been monitored for 10 years. At the 10-year mark, participants were given a psychiatric examination. Julie Pasco, BSc(Hons), at the University of Melbourne, and colleagues conducted their assessment using case-control and retrospective cohort methods. MDD was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria; smoking was self-reported. Pasco and colleagues found that smoking and depression had a significant association, especially for heavy smokers (>20 cigarettes/day).

There were 165 women with a diagnosis of MDD with 806 controls. Smoking was associated with a significantly higher odds ratio for MDD (1.46, 95% CI 1.03–2.07). For heavy smokers (>20 cigarettes/day), the odds ratio for MDD was more than twice that of non-smokers. Among the 671 women with no history of MDD at baseline, 13 out of 87 smokers (14.9%) and 38 out of 584 non-smokers (0.07%) developed MDD during the 10-year study period. Overall, after controlling for alcohol consumption and physical activity, smoking increased the risk of MDD by 93% (hazard ratio 1.93, 95% CI 1.02–3.69).

Funding for this research was provided by Eli Lilly. (Br J Psychiatry. 2008;193(4):322-326) –LS

US Youths More Commonly Prescribed Psychotropic Drugs Compared to Western European Counterparts

Prescriptions for psychotropic medications have been increasing throughout Western Europe and the United States for the last 10 years. In addition, previous research indicates that use of psychotropic medications is higher in the US. According to a cross-sectional study by Julie M. Zito, PhD, of the University of Maryland School of Pharmacy in Baltimore, and colleagues, youths 0–19 years of age are more likely to receive prescriptions for psychotropic drugs in the US than in Western Europe.

The researchers investigated administrative claims data from the year 2000 on insured youths from  Germany (n=356,520), the Netherlands (n=110,944), and the US (n=127,157). A population-based analysis of psychotropic medication use was performed according to children’s age group, gender, drug subclass pattern, and concomitant use. Results found that annual prevalence of any psychtropic medication in youths was 6.7% in the US, which is substantially greater than in both the Netherlands (2.9%) and Germany (2%). The US demonstrated ≥3 times greater antidepressant and stimulant prevalence than the Netherlands and Germany; antipsychotic prevalence was 1.5–2.2 times greater. While the atypical antipsychotic subclass represented 48% in the Netherlands and 5% in Germany, the US represented 66%. Though psychotropic drugs such as α-agonists, lithium agents, and antiparkinsonian agents were prescribed less in all three countries, rarely used anxiolytics were twice as prevalent in Dutch youths as in US and German youths. Prescription hypnotics were 50% as common as anxiolytics in Dutch and US youths; they were uncommon in German youths the most. Concomitant drug use was twice as prevalent in youths in the US (19.2%) as those in the Netherlands, and three times as those in Germany.

Zito and colleagues concluded that there are great differences in psychotropic medication treatment patterns between US youths and Western European youths. It is possible that such differences raise from direct-to-consumer (DTC) drug advertising, government regulation, reimbursement policies, diagnostic classification systems, and cultural beliefs concerning medication’s role in emotional and behavioral treatment. Further, a demographic explanation of this phenomenon suggests that the number of child psychiatrists per capita is higher in the US than in Western Europe.

The study was limited by the cross-sectional nature of the investigation and lack of diagnostic information of enrollees. In addition, that DTC advertising is allowed only in the US among the three countries is confounding as is the fact that US data were confined to children covered under the State Children’s Health Insurance Program. Lack of information on reimbursement patterns, differences in access to specialist care, and lack of information on over-the-counter drugs limited the study as well. (Child Adolesc Psychiatry Ment Health. 2008;2(1):26.) –ML

MDD and Anxiety May Worsen COPD Symptoms Leading to Increased Hospitalizations

Major depressive disorder (MDD) and other depressive disorders as well as generalized anxiety are frequently occurring comorbid conditions for patients with chronic obstructive pulmonary disease (COPD). Although the increased prevalence of these psychiatric conditions in patients with COPD is widely known, few studies have investigated the link between these conditions and COPD disease course, including frequency of COPD exacerbation and subsequent hospital stays. The effect of MDD and anxiety on COPD presentation is of particular importance as the mental health conditions can be treated, which may potentially alter the disease outcome for a patient with COPD.

Jean Bourbeau, MD, of the Respiratory Epidemiology and Clinical Research Unit of McGill University in Montreal, Canada, and colleagues, studied 491 patients with stable COPD for symptoms of MDD and/or anxiety. The authors hypothesized that COPD patients with comorbid MDD or anxiety would be at increased risk for a greater number of exacerbations and hospitalizations. All patients were gathered from respiratory departments of 10 hospitals in Beijing, China and were evaluated for MDD and anxiety symptoms as well as COPD progression at the study beginning. For study inclusion, patients had to be ≥30 years of age, have physician-diagnosed COPD, have no worsening of respiratory symptoms 4 weeks prior to study beginning, and have an expected survival rate of ≥6 months, among other criteria.

MDD and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale, which assesses symptom severity among hospital and primary care patients. COPD progression was measured by spirometry and bronchodilator response tests, assessment of cough production and chest wheeze, and self-report. Exercise capacity and quality of life were also evaluated. Patients were then evaluated once-a-month for 12 months to assess occurrence of exacerbations or hospitalizations.

Bourbeau and colleagues found that 112 patients had probable MDD while 47 had probable anxiety. During the study period, 876 symptom-based and 450 event-based exacerbations were recorded, and 183 of these symptom exacerbations led to hospitalization. When compared to patients without psychiatric disorders, patients with probable MDD had significantly increased rates of symptom-based and event-based exacerbations, increased mortality, and increased hospital stays that were longer than non-depressed patients. Patients with anxiety experienced more frequent symptom-based exacerbations and longer hospital stays, when compared to non-anxious patients.

They also found that depressed patients had a higher percentage of concurrent anxiety, had lower levels of education attained, were less likely to be married, and had increased rates of past exacerbations and hospitalizations. Patients with both probable MDD and anxiety had lower levels of self-efficacy and social support. These results also persisted after adjusting for confounding variables.

Bourbeau and colleagues concluded that their findings show that symptoms of depression and anxiety are causally linked to increased rates of exacerbations and hospitalizations for patients with COPD. This relationship may be due to depression effecting change in the immune system or affecting a patient’s ability to adapt to chronic symptoms as well as decreasing self-confidence, which may lead to poorer medication adherence. Thus, clinicians should note that treatment of MDD and anxiety may lead to better COPD treatment outcomes.

Funding for this research was provided by the Canadian Institute of Health Research. (Am J Respir Crit Care Med. 2008;178(9):913-920.) –CP

Psychiatric dispatches is written by Michelisa Lanche, Christopher Naccari, Carlos Perkins, Jr, and Lonnie Stoltzfoos.