Wednesday, January 16, 2019

Individuals With a Mental Disorder at Increased Risk for Subsequent Diagnoses

About 30% of men and 40% of women diagnosed with depression before age 20 will be diagnosed with an anxiety disorder within five years, and 40% of men and 50% of women will be diagnosed within 15 years, reports a study published today in JAMA Psychiatry. This strong association between depression and later anxiety was just one of many comorbidities identified in this study—one of the largest and most detailed examinations of comorbidity of mental disorders to date.

“To our knowledge, this is the first study to provide a comprehensive set of age- and sex-specific estimates of absolute risks associated with comorbid mental disorders,” lead author Oleguer Plana-Ripoll, Ph.D., of Aarhus University and colleagues wrote. “Our findings provide new insights into the complex nature of comorbidity, and the comprehensive nature of the analysis will provide an important foundation for future research.”

Plana-Ripoll and colleagues used health registry data from all individuals born in Denmark and residing in the country between 2000 and 2015; this encompassed 5.94 million individuals and about 84 million years of medical data. They grouped all ICD diagnoses within 10 categories of mental illness: behavioral disorders, developmental disorders, eating disorders, intellectual disability, mood disorders, neurotic disorders, organic disorders (for example, dementia), personality disorders, schizophrenia disorders, and substance use disorders. Next, they calculated the risks of an individual having a disorders within any two separate categories.

Overall, the presence of comorbidity was pervasive, with some categories of disorders having exceptionally strong odds of occurring together. For example, compared with an individual not diagnosed with a mental disorder, an individual diagnosed with a mood disorder was 30 times more likely to be diagnosed later with a personality disorder or a developmental disorder, and 20 times more likely to be diagnosed with schizophrenia or a substance use disorder.

The investigators also found that the risk of being diagnosed with a second mental illness is highest in the first six months after the diagnosis of the first disorder, and the increased risk persists for at least 15 years after the initial diagnosis.

Given this vast amount of data, the researchers developed an interactive visualization tool highlighting these various connections, which they hoped would assist clinicians in monitoring potential emerging comorbidity over time.

For related information, see the Psychiatric News article “Study Examines Connections Between Psychiatric, Neurological Disorders.”

photo: iStock/SeventyFour

Tuesday, January 15, 2019

Parents Often Unaware of Adolescents’ Suicidal Ideation, Study Shows

Parents are often unaware that their adolescent children are thinking about suicide or death, according to a report in the journal Pediatrics. Moreover, when parents do believe their children are having such thoughts, the children often deny them.

Given these findings, it is apparent that brief screens used at routine checkups are not detecting many adolescents at risk for suicide, wrote Jason D. Jones, Ph.D., of the Department of Child and Adolescent Psychiatry at Children’s Hospital of Philadelphia. “This highlights the urgent need for continued training of pediatric primary care physicians in the evaluation and management of suicidal ideation and the importance of collecting information from multiple informants and rectifying discrepant reports.

Jones and colleagues analyzed data on more than 5,000 adolescents and their parents or stepparents from the Philadelphia Neurodevelopmental Cohort. The latter is a research initiative combining genetic, neurodevelopmental, neuroimaging, and behavioral data on more than 9,000 adolescents aged 11 to 21 recruited from a large pediatric health network.

During a computerized, structured clinical interview, adolescents were asked these questions: “Have you ever thought about killing yourself?” and “Have you ever thought a lot about death or dying?” Parents answered the same questions about their adolescents’ suicidal thoughts and thoughts of death.

Half of all parents were unaware of their adolescents’ suicidal thoughts, and three-quarters of the parents were unaware that their children harbored recurrent thoughts of death. Moreover, when parents did report that their adolescent children had thoughts of suicide or death, the children frequently denied it: 48.4% of adolescents denied thinking about killing themselves, and 67.5% denied thoughts of death reported by parents. Age and previous psychiatric treatment were associated with better parent-child agreement.

In an accompanying editorial, Khyati Brahmbhatt, M.D., and Jacqueline Grupp-Phelan, M.P.H., M.D., of San Francisco Benioff Children’s Hospital, agreed with the recommendations that multi-informant assessments should be used and disagreements should be carefully explored.

“Including parents and other sources of information in assessments may help capture a larger percentage of adolescents who are at risk,” they wrote. “Further research to improve our understanding of factors driving the denial of symptoms by adolescents and its relation to the risk for suicide attempts is needed. It may help inform screening as well as interventions and ultimately enhance our ability to effectively address suicide in adolescents.”

For related information see the Psychiatric News article "Irritability in Childhood May Point to Teens at High Risk for Suicide."

(Image: fizkes/

Friday, January 11, 2019

Study Suggests Actions to Improve Compliance With Depression Treatment

Treatment guideline recommendations are not being followed for a large proportion of patients with major depressive disorder, suggests a study published today in Psychiatric Services in Advance. The authors suggest that improvement in multiple areas—such as treatment practices and health insurance coverage—are needed.

“Our research found that most patients were not receiving antidepressants or psychotherapy after the first five months following their initial diagnosis of major depressive disorder,” wrote Fraser W. Gaspar, Ph.D., M.P.H., of MDGuidelines, a health care consulting organization, and colleagues. “Furthermore, when treatment was utilized, antidepressant and psychotherapy adherence was low, and the starting antidepressant dosages were often outside guideline recommendations.”

The study analyzed claims data from the 2007-2016 records of IBM MarketScan research databases for nearly 25,000 patients whose ICD (International Classification of Diseases) code indicated a diagnosis of “single-episode, major depressive disorder.” The MarketScan population is drawn from a sample of employees who mostly work for larger employers and have employer-provided health insurance. Researchers tracked use of pharmacotherapy and psychotherapy and analyzed drug codes attached to each participant’s pharmaceutical claims to determine the strength and class of prescribed antidepressants.

The study’s major findings include the following:

  • Most patients (55%) had discontinued all treatment, both psychotherapy and medication, by the fifth month after being diagnosed with major depressive disorder.
  • A shorter time from diagnosis to treatment and a lower percentage of out-of-pocket costs paid by the patient were associated with increased medication adherence and intensive psychotherapy use. In contrast, participants in high-deductible and consumer-driven health plans were most likely to receive no treatment or treatment with a prescription only.
  • About one-third of patients were prescribed dosages outside of the dosing regimen noted in the APA Practice Guideline for the Treatment of Major Depressive Disorder, with more dosages below the recommendation (23%) than above (11%). However, the authors noted some of the variance might reflect off-label use of the medications.
  • Less than half of patients with depression were adherent to antidepressant treatment in the acute and continuation phases (defined as approximately the first four months and eight months, respectively, after starting treatment). Patients with greater depression severity had significantly lower adherence rates, the authors noted.

“Modifiable characteristics, such as starting treatment immediately after diagnosis of major depressive disorder and lowering out-of-pocket expenses, were associated with antidepressant adherence and intensive psychotherapy utilization. Furthermore, patients who used mail-order prescriptions for antidepressants had higher odds of adherence,” the authors wrote. Since increased cost sharing cut pharmaceutical adherence, health policymakers should consider expanding mental health benefits to improve overall savings attributable to improved health outcomes, the authors noted.

For related information, see the Psychiatric News article “Refusal, Dropout Rates Differ Between Patients Receiving Psychotherapy, Pharmacotherapy.”

(Image: iStock/FilippoBacci)

Thursday, January 10, 2019

Some Common Medications Found to Help People With Serious Mental Illness

Common medications used to fight cholesterol, high blood pressure, and diabetes may be useful in lowering risk of self-harm and psychiatric hospitalization for people with a serious mental illness (SMI) such as bipolar disorder, schizophrenia, or nonaffective psychosis, according to a study published yesterday in JAMA Psychiatry.

In the study, Joseph F. Hayes, Ph.D., of University College London and an international team of colleagues analyzed data from the health records of 142,691 Swedish patients aged 15 and older who had an SMI and were treated with psychiatric medication from October 2005 through December 2016. The data also included whether the patients were treated with statins for cholesterol, L-type calcium channel blockers for high blood pressure, or metformin for type 2 diabetes. The researchers then compared rates of self-harm and psychiatric hospitalization in these patients to determine whether they had been taking one of the three types of medications at the time of harming themselves and/or psychiatric hospitalization.

The researchers found that patients who had bipolar disorder and were taking one of the three types of medications were 8% to 20% less likely to experience psychiatric hospitalization and 19% to 27% less likely to harm themselves. Patients with schizophrenia who were taking one of the three types of medications were 20% to 27% less likely to experience psychiatric hospitalization and 36% to 70% less likely to harm themselves. Patients with nonaffective psychosis who were taking statins or metformin were 20% and 15% less likely to experience psychiatric hospitalization, respectively, and those taking L-type calcium channel blockers were 44% less likely to harm themselves.

“Each of these drugs has a theoretical basis for effectively reducing psychiatric symptoms,” Hayes and colleagues wrote. They noted that the three types of medications work on some of the processes thought to cause psychiatric disorders. For example, systemic and neuroinflammation are linked to psychiatric disorders, and statins are anti-inflammatory. Additionally, high cholesterol, high blood pressure, and diabetes are more common in people with SMI, they noted.

“If substantiated, this study has considerable implications for clinical practice and drug development. The study drugs … are globally licensed, commonly used, cheap, and relatively safe medications. They are therefore ideal candidates for repurposing,” Hayes and colleagues wrote. “Understanding their mode of action on the central nervous system may facilitate better understanding of the pathophysiology of SMI and offer opportunities for innovative pharmacotherapy development.”

For related information, see the Psychiatric News article “Psychiatrists Face Barriers to Managing Common Medical Conditions.”

(Image: iStock/MJ_Prototype)

Wednesday, January 9, 2019

FDA Approves Marketing of Eye-Tracking Test for Detecting Concussion

The Food and Drug Administration has cleared for marketing an eye-tracking test that can help determine whether a patient has experienced a concussion.

The device, known as EyeBOX, uses a camera to measure a patient’s eye movements in response to a stimulus. Such information can help physicians and other health care professionals better assess the extent of a patient’s brain injury.

“Other diagnostics require a baseline test, typically generated at the beginning of a sport season, pre-injury, [which] is compared to subsequent test results at the time of a suspected concussion. In many situations, a baseline concussion assessment is not feasible, especially when evaluating trauma patients in the emergency room,” according to a press statement by Oculogica, the manufacturer of the device. “EyeBOX’s unique eye-tracking algorithm enables it to be baseline-free, a major advancement for the field.”

The FDA’s decision to approve the test for marketing was based in part on the results of a trial of 282 patients who presented with a suspected head injury to the emergency departments and sports medicine clinics at six independent clinical sites. The researchers compared the results of the EyeBOX test with those of a clinical reference standard for concussion. According to Oculogica, “The study showed that the EyeBOX had high sensitivity to the presence of concussion and that a negative EyeBOX result is consistent with a lack of concussion, thus providing objective data for health care providers to aid in the evaluation of patients with suspected TBI.”

EyeBOX is intended for patients aged 5 to 67 years, according to Oculogica.

For related information, see the Psychiatric News article “FDA Clears the Way for First Blood Test to Evaluate Head Injuries” and the Journal of Neuropsychiatry and Clinical Neurosciences article “Saccadic Impairment Associated With Remote History of Mild Traumatic Brain Injury.”

(Image: iStock/CoffeeAndMilk)

Tuesday, January 8, 2019

Cancer Patients at Increased Risk for Suicide Within a Year After Diagnosis

Patients with cancer are at an increased risk of suicide in the first year after diagnosis compared with the general population,according to a report in the journal Cancer. The risk differs by type of cancer, with pancreatic and lung cancer having the highest risk.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” wrote Anas M. Saad, M.D., of Ain Shams University, Cairo, and colleagues.

Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, the researchers calculated observed/expected (O/E) risk ratios for more than 4 million patients diagnosed with cancer between 2004 and 2014 in the United States. The O/E risk ratio represents the observed number of patients who died from suicide in the first year after diagnosis compared with a demographically similar population within the same period. Mortality data for the general population were collected by the National Center for Health Statistics.

A total of 1,005,825 cancer patients died within the first year after their diagnosis. Suicide was the cause of death for 1,585 of these patients (0.16%). The O/E risk ratio for cancer patients was 2.52, representing a more than two-and-a-half times greater risk of suicide than in the general population.

The patients with the highest increases in suicide rates were those who had been diagnosed with pancreatic cancer or lung cancer: their O/E ratios were 8.01 and 6.05, respectively.

“Social support for patients with cancer plays an integral role in suicide prevention,” Saad and colleagues wrote. “The most effective forms of support seem to be peer support, partner support, and one-to-one professional support. Discussing the quality of life after the diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer.”

For related information, see the Psychiatric News article “Researcher Looks at Improving Well-Being of Families Affected by Cancer.”

(Image: Pattanaphong Khuankaew/

Monday, January 7, 2019

Some Levels of Alzheimer’s Biomarkers May Differ Between African Americans, Whites

African-American individuals on average have lower levels of the tau protein compared with white individuals, reports a study published today in JAMA Neurology. Tau, along with amyloid beta, are two proteins strongly associated with Alzheimer’s disease (AD) and considered key biomarkers for diagnosing AD.

“To our knowledge, our study is the first to examine racial differences in molecular biomarkers of AD in which the cohort contributed data for both amyloid concentrations as seen on PET scan and CSF [cerebrospinal fluid] concentrations of [amyloid and tau],” wrote lead author John C. Morris, M.D., of the Knight Alzheimer Disease Research Center at Washington University School of Medicine in St. Louis and colleagues. “Caution is needed in interpreting our results until they can be confirmed (or refuted) with subsequent analyses in larger cohorts to carefully explore the influences of socioeconomic status, comorbid diseases, and other factors that may contribute to racial differences.”

Morris and colleagues analyzed data from 1,255 adults who were participating in Alzheimer’s studies at the Knight Research Center; this sample included 173 African Americans. As part of these studies, the participants received brain scans and CSF samples were taken to assess for Alzheimer’s biomarkers. In both African-American and white participants, about two-thirds of individuals had normal cognition while the other one-third had Alzheimer’s or some other cognitive impairment.

The researchers found no racial differences in the average brain or CSF levels of amyloid beta among the participants. However, African-American participants had significantly lower CSF tau levels compared with white participants. Average CSF concentrations of tau were 293.65 pg/mL for African Americans and 443.28 pg/mL for whites. The discrepancy in tau levels between African Americans and whites was much larger among participants who had the ε4 allele of the APOE gene; APOEε4 is considered a genetic risk factor for Alzheimer’s.

“Given recent evidence that APOEε4 influences tau pathogenesis and tau-mediated neurodegeneration independent of [amyloid beta], … it is possible that the interactions of APOEε4 with tau in African-American individuals differs from its interactions with tau in white individuals,” Morris and colleagues wrote.

“Older African-American individuals, a population that is rapidly growing, are at greater risk of AD than are older white individuals, but are underrepresented in clinical research studies,” wrote Lisa Barnes, Ph.D., of Rush University Medical Center in an editorial accompanying the study. “[A]s the field moves toward a biological definition of AD, the underinclusion of minority populations in AD research will significantly hinder our progress as a field, and the race to end AD will not be shared with our most vulnerable, at-risk populations.”

For related information, see the Psychiatric News article “Are Amyloid and Tau Good Biomarkers For Alzheimer’s Disease?


Friday, January 4, 2019

Perinatal and Postpartum Distress Increases Risk for Developmental Delays

Children born to mothers who have persistent anxiety from late pregnancy to three years postpartum have an increased risk of delays in communication and personal-social development, according to a study in the Journal of Affective Disorders. The findings suggest the need for increased efforts to identify mothers with perinatal and postpartum distress in an effort to mitigate the associated developmental delays.

Muhammad Kashif Mughal, M.B.B.S., Ph.D., of the University of Calgary and colleagues evaluated data from the three-year follow-up to the All Our Families (AOF) study, an ongoing study of mothers and children in Calgary, Alberta, Canada. The AOF study, begun in 2008 as the All Our Babies study, includes self-reported assessments of mothers’ distress at multiple time points ranging from before the 25th week of gestation up to three years postpartum. Also included are parent-reported tools to measure child development at age 3 across five domains: communication, gross motor, fine motor, problem solving, and personal-social. For the current study, the researchers analyzed data from 1,983 mother-child pairs.

Overall, 4.7% to 6.4% of the mothers reported depressive symptoms at four time-points: <25 weeks gestation, 34 to 36 weeks gestation, 4 months postpartum, and one year postpartum. Also, 13.8% to 18.5% of mothers reported anxiety symptoms at six time points: <25 weeks gestation, 34-36 weeks gestation, 4 months postpartum, one year postpartum, two years postpartum, and three years postpartum. After applying statistical models, the researchers found that persistent subclinical and high anxiety symptoms were associated with an increased risk of communication delay at age 3 years. They also found that persistent high anxiety symptoms and early postpartum depression were associated with an increased risk of personal-social delay at age 3 years.

The researchers chose to evaluate multiple time points for a more complete picture of risk over time. “[F]ocusing on maternal distress at one time point is problematic because recent studies characterizing perinatal mental health problems suggest that mental health symptoms are not isolated incidents and tend to recur or continue for a majority of women,” Mughal and colleagues wrote.

The results suggested an insignificant association between maternal distress and the remaining domains of child development (gross motor, fine motor, and problem solving). However, the researchers identified other risk factors for these domains, such as maternal age greater than 35 years, male sex, and preterm birth for gross motor delays; low maternal education and male sex for fine motor delays; and low family income and preterm birth for problem-solving delays. Having a family with two or more children was a protective factor for fine motor development.

“The study provides evidence for redefining ‘at-risk’ women as those traditionally identified as high risk as well as those identified as having subclinical symptoms over time,” Mughal and colleagues concluded. “As such, these findings call for a shift in the current model of health care … to approaches that capture the spectrum of chronicity and severity to ensure appropriate care that supports the improvement of maternal mental health outcomes and development in preschool children.”

(Image: iStock/shapecharge)

Thursday, January 3, 2019

Ketamine Found Effective for Patients With Anxious Treatment-Resistant Depression

Patients with anxious depression—major depressive disorder (MDD) with high levels of anxiety—are known to have a poorer response to commonly used antidepressants than those with MDD. A small study published in Depression & Anxiety now suggests intravenous (IV) ketamine may be able to reduce symptoms in patients with anxious depression. The study found patients with and without anxious depression experienced similar symptom improvements within 24 hours of receiving a ketamine infusion.

Naji C. Salloum, M.D., of Harvard Medical School and colleagues compared the effectiveness of IV ketamine to that of midazolam (preoperative sedative) in relieving symptoms of depression with anxiety. They randomized 99 patients with treatment-resistant depression to one of five arms: a single dose of IV ketamine (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg) or midazolam (0.045 mg/kg). Forty-five of those patients had anxious depression as defined by a Hamilton Depression Rating Scale Anxiety/Somatization score of at least 7.

Using several depression scales, the researchers evaluated the patients’ symptoms on the first and third days after treatment. Although all patients responded to their treatment (either ketamine or midazolam), those who had received ketamine experienced greater improvements in their symptoms. Furthermore, there were no significant differences in response between the anxious and nonanxious patients.

“[The] results of the present study did not demonstrate differential efficacy of ketamine for the treatment of either anxious or nonanxious depression, pointing to the possibility that intravenous ketamine treatment may be equally efficacious in treating subjects with or without anxious [treatment-resistant depression]. These results are still exploratory and future larger and adequately powered studies designed to specifically test this aim are warranted,” Salloum and colleagues wrote.

The researchers also noted that anxious patients experienced a lower level of dissociative symptoms 40 minutes after infusion compared to nonanxious patients, a phenomenon that they suggested may be attributable to a higher proportion of benzodiazepine use in patients with anxious depression.

For related information, see the Psychiatric News article “Ketamine Shown to Reduce Suicidal Ideation in Severely Depressed Patients.”

(Image: iStock/slobo)

Wednesday, January 2, 2019

Seniors With Depression May Be at Heightened Risk of Hip Fracture Before Starting Antidepressants

Despite several observational studies demonstrating that older patients taking antidepressants are at a higher risk of falls and fractures, it has remained unclear whether the use of the medication causes the increased risk. A study published today in JAMA Psychiatry suggests that older adults may be at higher risk of hip fracture even before they start taking antidepressants.

While the findings raise questions about the association between antidepressant drug use and hip fracture, study authors Jon Brännström, M.D., of Umeå University in Sweden and colleagues cautioned that doctors should continue to limit the prescription of antidepressants to older adults.

For the study, Brännström and colleagues focused on adults aged 65 years or older in Sweden who had filled a prescription for antidepressants between July 1, 2006, and December 31, 2011. The authors compared hip fracture data from one year before to one year after the date that the participant first filled the prescription for an antidepressant. Each participant was matched with one control (an adult of the same sex and age who did not use antidepressants during the study period). In total, 408,144 adults (mean age, 80.1 years) were included in the analysis.

The authors found that participants in the antidepressant group had more than twice as many incidents of hip fracture before and after the initiation of treatment than did those who did not take antidepressants. The odds ratio (OR) for the association between any antidepressant use and hip fracture peaked 16 to 30 days before the prescription was filled (OR, 5.76)—a pattern that was consistent in all separate analyses of age groups, of men and women, and of the three most commonly prescribed antidepressants (citalopram hydrobromide, mirtazapine, and amitriptyline hydrochloride), the authors noted.

“Based on our results, we suggest that older people with depression have an increased risk of hip fracture before starting antidepressant treatment, owing to a high burden of comorbidity and confounding by indication,” Brännström and colleagues wrote. “Even if antidepressant drug use does not increase the risk of hip fracture, the prescription of antidepressants to older people should be restrictive, as the evidence for positive effects is limited.”

In an accompanying editorial, Andrea Iaboni, M.D., D.Phil., of the University of Toronto and Donovan T. Maust, M.D., M.S., of the University of Michigan recommended that doctors continue to communicate the potential risks of antidepressants for older patients: “We suggest that clinicians would still be wise to inform patients about the potential risk of falling and fractures that may follow antidepressant use to allow patients to make an informed decision about treatment,” they wrote. “[F]or most older adults, the toll of untreated depression will likely outweigh the potential risks associated with antidepressant use, including falls or fractures.”

Iaboni and Maust also recommended that doctors avoid prescribing sedating or anticholinergic agents, start patients on a low dose that can be increased over time, and review other medications that patients may be taking that could increase risk of falls and fractures.

For related information, see the Psychiatric News article “Patients Taking Psychotropic Medications Found to Be at Elevated Risk of Fractures.”

(Image: iStock/Shidlovski)

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