Tuesday, January 31, 2017

FDA Approves Latuda for Use in Adolescents With Schizophrenia


The Food and Drug Administration (FDA) on Friday approved a supplemental New Drug Application for Latuda (lurasidone HCl) for the treatment of schizophrenia in adolescents aged 13 to 17 years. 

Latuda is already approved in the United States for the treatment of adults with schizophrenia and for the treatment of adults with major depressive episodes associated with bipolar I disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.

According to a statement on the website of Sunovion, which manufactures Latuda, the approval is based on results from a randomized, double-blind, placebo-controlled, six-week study in which adolescent patients with schizophrenia received fixed doses of Latuda 40 mg/day, Latuda 80 mg/day, or placebo. At study endpoint, Latuda 40 mg/day and 80 mg/day were associated with statistical and clinical improvement in symptoms of schizophrenia compared with placebo. Latuda was also generally well tolerated with limited effects on weight and metabolic parameters. 

“The impact on development and poor prognosis frequently associated with schizophrenia that begins in adolescence underscores the need for treatment that is both well-tolerated and effective,” said study investigator Robert Findling, M.D., M.B.A., director of child and adolescent psychiatry at the Johns Hopkins University School of Medicine, in the Sunovion statement. “The availability of Latuda provides health care providers with an important new option for helping adolescents with this illness that is chronic and severely disabling.”

For related information, see the Psychiatric News article “Early Intervention Trial in Youth at Risk for Psychosis Shows Improved Symptoms.”

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Monday, January 30, 2017

Exposure to Synthetic Oxytocin May Increase Risk of Postpartum Depression, Anxiety


A study published today in Depression and Anxiety suggests that pregnant women who receive synthetic oxytocin (Pitocin) during or shortly after delivery may be at a greater risk of postpartum depression or anxiety than those who are not exposed to the synthetic hormone. Understanding the relationship between oxytocin and postpartum depression or anxiety could help to identify women at greatest risk of these disorders, which can have adverse effects on offspring.

For decades, synthetic oxytocin has been regularly administered to induce/advance labor and prevent post-delivery hemorrhages. More recently, studies have suggested oxytocin—known to have positive effects on mood and maternal-child bonding—may be able to be used to treat perinatal depression and anxiety.

For the current study, Kristina Deligiannidis, M.D., of the Feinstein Institute for Medical Research in New York and colleagues analyzed data on peripartum patients who received intravenous synthetic oxytocin between 2005 and 2014 at University of Massachusetts Memorial Health Care. 

The sample included 9,684 deliveries with peripartum synthetic oxytocin exposure (defined as within two weeks of delivery date) and 37,048 deliveries without peripartum synthetic oxytocin exposure. Depressive or anxiety disorders, defined as record of diagnosis and/or receipt of antidepressant or anxiolytic medication prescription, were divided into three timeframes: pre-pregnancy (diagnosis/prescriptions more than one year before delivery), pregnancy (diagnosis/prescription during pregnancy or 40 weeks ahead of delivery date), and postpartum (diagnosis/prescription one year following delivery).

The researchers found that exposure to peripartum oxytocin increased the risk of depression or anxiety in the first postpartum year by about 32% in women with no history of pre-pregnancy depression or anxiety. In women with a history of pre-pregnancy depressive or anxiety disorder, exposure to the peripartum oxytocin increased the risk of depression or anxiety by 36%. These risks were still present even if the analysis factored in multiple births from one woman, for example by only looking at index deliveries (each woman’s first birth) or analyzing one random birth from women with multiple deliveries.

“Our data support the idea that synthetic oxytocin administration during labor has a negative impact on postpartum mood,” the researchers wrote. However, they noted, “It is important to note that the effect of synthetic oxytocin administration on endogenous oxytocin levels is unclear, and nothing about endogenous oxytocin levels can be inferred from our dataset…”

“Since synthetic oxytocin is such an important and commonly used medicine for peripartum women, further research should examine dose, duration, timing, and reason for treatment so that we can better identify which women may be at risk for developing postpartum depression and anxiety,” Deligiannidis said in a press release.

For related information, see the Psychiatric News article “Determining Onset Timing of Postpartum Depression May Lead to Improvements in Treatment.”

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Friday, January 27, 2017

Low Birth Weight May Increase Risk of Psychiatric Disorders Later in Life


Children and adolescents who were born early and/or at low birth weight are known to be at a higher risk of physical and neurodevelopmental delays and psychiatric illness. A study appearing this week in Pediatrics now suggests a low weight at birth may increase the risk of psychiatric disorders and lower cognitive function later in life as well. 

The findings “underscore the need for long-term follow-up of low birth weight survivors through adolescence and adulthood, focusing on mental health,” Astrid M. W. Lærum, M.D., of the Norwegian University of Science and Technology in Trondheim, Norway, and colleagues wrote. The findings also suggest the importance of asking patients about their birth weight during a psychiatric evaluation.

For the study, the researchers compared psychiatric symptoms and cognitive function in adults aged 26 who were participants in a long-term follow-up study of children born with a low birth weight. The participants were divided into three groups: 44 adults were in the very low birth weight group (born preterm at a weight of ≤1500 grams [3.3 pounds]), 64 in the small for gestational age (born at term with a birth weight <10th percentile) group, and 81 in the control group (born at term with a birth weight ≥10th percentile).

All participants were evaluated using the MINI-International Neuropsychiatric Interview: M.I.N.I. Plus, Norwegian version, and the Global Assessment of Functioning. The prevalence of psychiatric disorders from follow-ups at age 14 and 19 were also included in analysis. 

The very low birth weight (VLBW) group had a significantly higher overall prevalence of psychiatric disorders (n=16, 36%) compared with the control group, including anxiety (n=12, 27%), mood (n=8, 18%), and somatoform disorders (n=4, 9%). The small for gestational age (SGA) group had a significantly higher overall prevalence of psychiatric disorders (n=24, 38%) compared with the control group, including anxiety (n=13, 20%), mood (n=9, 14%), and somatoform disorders (n=6, 9%). In the control group, 11 (14%) participants had a psychiatric disorder, including seven with anxiety disorders and five with substance use disorders. Participants in both low birth weight groups were also found to have lower functioning scores than controls. 

“According to our longitudinal analysis, the probability of psychiatric disorders in the term SGA group increased substantially into adulthood,” the authors wrote. “Although the pre- and perinatal differences between the VLBW and the SGA are most apparent, we speculate … that the two groups may share some prenatal exposure, contributing to their similar overall adult morbidity and similar profile of non-substance use disorders.”

For related information, see the Psychiatric News article “Extremely Low Birth Weight May Be Risk Factor for Psychiatric Illness.” 
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Thursday, January 26, 2017

Epigenetic Changes May Link Socioeconomic Status With Altered Brain Function, Depression


Although lower socioeconomic status is associated with an increased risk of mental illness, including anxiety and depression, little is known of the biological processes that may mediate this association. A study appearing in Molecular Psychiatry suggests a biological pathway through which lower socioeconomic status may contribute to altered brain function and future risk of depression. 

“[I]f replicated, the risk pathway identified here could represent a discrete biomarker that could be targeted by novel strategies for personalized treatment and prevention,” Johnna Swartz, Ph.D., a postdoctoral associate in the Department of Psychology and Neuroscience at Duke University, and colleagues wrote.

For the study, the researchers analyzed epigenetic, neuroimaging, and behavioral data collected from 132 youth who were participants in the Teen Alcohol Outcomes Study (a multiyear study examining the association between the development of depression and alcohol use disorders in adolescence). Adolescents were between 11 and 15 years old during the first wave of data collection, 13 and 18 at Wave 2, and 14 and 19 at Wave 3.

Lower socioeconomic status—as defined by parental education and income—at Wave 1 predicted greater increase in methylation of the proximal promoter region of the serotonin transporter gene SLC6A4 two years later (Wave 2), with or without a family history of mental illness. Analysis of fMRI data revealed that increases in SLC6A4 methylation from Wave 1 to Wave 2 were also associated with increases in threat-related amygdala reactivity over the same period. In adolescents with a positive family history of depression, greater increases in reactivity from Wave 1 to Wave 2 prospectively predicted greater increases in depressive symptoms from Wave 2 to Wave 3; there was no such relationship in adolescents without a family history of depression.

“It is possible that these high-risk adolescents experience additional forms of chronic adversity such as parental neglect or familial discord uncommon among their low-risk counterparts and that this additional exposure is necessary to trigger symptoms of depression,” Swartz and colleagues concluded. “[O]ur results identify a specific biological pathway through which broader environmental adversity may act to drive individual vulnerability for depression among at-risk adolescents.”

For related information, see the Psychiatric News article “Researchers Tackle Complexity of Intergenerational Stress Transmission.”

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Wednesday, January 25, 2017

Low-Dose Naltrexone May Mitigate Severity of Opioid Withdrawal During Detox


An extended-release injectable form of naltrexone (XR-naltrexone) was approved years ago to reduce the risk of relapse in patients with opioid use disorder, but the recommendation that patients abstain from opioids for up to 10 days before receiving the opioid antagonist can be a significant barrier to its use. A study published in AJP in Advance now suggests a low-dose naltrexone treatment regimen may increase the likelihood that opioid-dependent patients receive XR-naltrexone treatment.

“By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during detoxification, this strategy has the potential to considerably increase patient acceptability of, and access to, antagonist therapy,” Maria Sullivan, M.D., Ph.D., of the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons and colleagues, wrote.

The researchers randomly assigned 150 patients seeking treatment for heroin or prescription opioid dependence to one of two outpatient detoxification regimens: naltrexone-assisted detoxification or buprenorphine-assisted detoxification.

As described in AJP, “Naltrexone-assisted detoxification lasted seven days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications” to alleviate residual withdrawal symptoms. In contrast, “[b]uprenorphine-assisted detoxification included a seven-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone.” Patients in both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone at week 5.

Compared with those in the buprenorphine-assisted detoxification group, participants assigned to naltrexone-assisted detoxification were significantly more likely to receive XR-naltrexone (56.1% compared with 32.7%) and receive the second injection at week 5 (50.0% compared with 26.9%). No overdoses occurred among study participants. A secondary analysis found that prescription opioid users were significantly more likely to receive first and second injections of XR-naltrexone than patients using heroin.

“Our findings support the conclusion that a seven-day opioid detoxification with gradually ascending doses of oral naltrexone is a well-tolerated outpatient procedure, with a success rate comparable to inpatient induction,” the authors wrote. “For heroin-using individuals with greater severity of opioid dependence, further work is needed to make rapid induction more feasible. This outpatient induction strategy may be improved by permitting more flexible oral naltrexone dosing and more rapid transition to XR-naltrexone, thus minimizing the risk of dropout.”

For related information, see the Psychiatric News article “HHS Takes Actions to Expand Treatment, Research in Opioid Crisis.”

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Tuesday, January 24, 2017

When Is Depression 'Treatment Resistant'?


What leads a clinician to conclude that a patient with depression is “treatment resistant” and thereby eligible for alternative nonpharmacological interventions—such as vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS)?

In an article appearing in the January issue of JAMA Psychiatry, Charles Conway, M.D., Mark George, M.D., and Harold Sackheim, Ph.D., wrote that the lack of a consensus definition around what constitutes treatment-resistant depression (TRD) “limits the ability to do comparative treatment research, to understand the biological underpinnings of TRD, and produces ambiguous medical insurance coverage issues.”

Drawing on data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the authors proposed a definition for TRD: failure to respond to two trials of an antidepressant prescribed at an adequate dose for an adequate duration of time.

Conway (pictured above), a professor of psychiatry and director of the Treatment Resistant Depression and Neurostimulation Clinic at Washington University, St. Louis, told Psychiatric News that in the absence of a consensus definition of TRD, patients often receive multiple trials of medication. “Our experience has been that when faced with patients who do not respond to a series of medications, clinicians typically continue to give more similar medications, despite there being no evidence to support that the fifth or sixth medication will work,” he said.

In STAR*D, patients with MDD received sequential treatment with antidepressants or psychotherapy using evidence-based antidepressant treatment strategies. At each stage of treatment, the likelihood that patients would respond decreased.

In the JAMA Psychiatry article, Conway and colleagues wrote that the “inflection point at which resistance markedly increased was level 3 (two adequate dose-duration treatments).” At that point, fewer than 1 in 5 patients remitted, they noted. “At subsequent trials (level 4) treatment failure rose to 90 percent,” Conway and colleagues wrote.

“After failure of two adequate dose-duration trials of antidepressants, augmentation strategy, or psychotherapy, a precipitous decrease to a remission rate of 5 percent or less was observed,” they wrote. “We believe this represents a starting point for operationally defining TRD.”

For more in-depth coverage on this subject, see the Psychiatric News PsychoPharm article “When Is Depression ‘Treatment Resistant’?



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Monday, January 23, 2017

Spousal Loss Found to Increase Risk of Alcohol Use Disorder


Spousal loss due to divorce or death appears to be associated with an enduring risk of alcohol use disorder (AUD), but remarriage may help to reduce this risk, according to a study published today in AJP in Advance.

“The pronounced elevation in AUD risk following divorce or widowhood, and the protective effect of both first marriage and remarriage against subsequent AUD, speaks to the profound impact of marriage on problematic alcohol use and the importance of clinical surveillance for AUD among divorced or widowed individuals,” lead author Kenneth Kendler, M.D., of Virginia Commonwealth University and colleagues wrote. 

The researchers assessed the records of nearly one million married individuals in Sweden to identify the association between divorce or widowhood and AUD occurrences (identified using medical, criminal, and pharmacy registries). The researchers controlled for potential confounding factors such as age, education, and family history of alcohol use. 

Divorce was strongly associated with both a risk of a first AUD occurrence (hazard ratio of 5.98 in men and 7.29 in women) and AUD relapse (hazard ratio of 3.20 in men and 3.56 in women). These risks were higher in people with a family history of AUD or who had prior externalizing behaviors. Remarriage following a divorce was associated with a large decline in first AUD occurrence in both sexes (hazard ratio of 0.56 in men and 0.61 in women) 

Widowhood also increased AUD risk in both sexes (hazard ratio of 3.85 in men and 4.10 in women). In women, widowhood had a stronger association with risk for future AUD if the spouse did not versus did have a lifetime history of AUD (hazard ratio of 3.69). 

“We found, in both sexes, a much larger effect on risk for AUD of divorce when the spouse did not versus did have a history of AUD. We saw a similar effect with widowhood but only in females,” the authors wrote. “These results suggest that it is not only the state of matrimony and the associated social roles that are protective against AUD. Rather, they are consistent with the importance of direct spousal interactions in which one individual monitors and tries to control his or her spouse’s drinking. A non-AUD spouse is likely to be much more effective at such control than a spouse with AUD.”

For related information, see the American Journal of Psychiatry study “Effect of Marriage on Risk for Onset of Alcohol Use Disorder: A Longitudinal and Co-Relative Analysis in a Swedish National Sample” and Psychiatric News article “Marriage May Decrease Future Risk of Alcohol Use Disorder.”

(Image: iStock/TravisLincoln)



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Thursday, January 19, 2017

History of Depression, Gestational Diabetes May Increase Risk of Postpartum Depression


A nationwide study that included more than 700,000 women in Sweden has found that gestational diabetes raises the risk of postpartum depression (PPD) in first-time mothers. In women who had a history of depression, pre-gestational diabetes was also a moderate risk factor for PPD.

These and other findings of the study may help to shed light on the relationship between depression and other pre- and perinatal PPD risk factors, the study authors said.

Michael Silverman, Ph.D., an assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai and colleagues examined more than a dozen risk factors for PPD—such as gestational age at delivery, mode of delivery, and birth weight—and their association with PPD in women with and without a history of depression.

As they described Wednesday in the journal Depression and Anxiety, the researchers found that women with a history of depression were more than 20 times more likely to experience PPD than mothers without a previous clinical diagnosis of depression—a risk that was slightly increased if the mother also had pre-gestational diabetes or a preterm delivery (delivery at 32 to 36 weeks’ gestation).

Preterm delivery at 32 weeks’ gestation or earlier, instrument-assisted or cesarean delivery, and younger age (24 or younger) increased PPD risk in women without a history of depression. Giving birth after age 35 was associated with PPD risk in all women regardless of depression history.

“[F]or the first time, we show how maternal and obstetric risk factors for PPD may differ between new mothers with and without a history of depression,” the authors wrote. Based on the differences in risks they observed, the authors suggested that there may be different causal pathways of PPD in women with and without a history of depression

For related information, see the Psychiatric News article “Determining Onset Timing of Postpartum Depression May Lead to Improvements in Treatment.”

(Image: pio3/Shutterstock)

Wednesday, January 18, 2017

Modafinil May Help Improve Memory in Patients With Remitted Depression


Cognitive dysfunction is known to be a core symptom of depression that tends to persist even after mood improves. A study published in Biological Psychiatry suggests that modafinil—a wake-promoting agent approved to treat patients with narcolepsy—might be able to help patients with remitted depression who are experiencing cognitive deficits.

Past studies have highlighted the cognitive-enhancing effects of modafinil in patients with schizophrenia and attention-deficit/hyperactivity disorder as well as healthy controls, but few have looked at the potential of the medication to treat cognitive deficits in patients with remitted depression.

For the current study, Barbara Sahakian, Ph.D., of the University of Cambridge and colleagues recruited patients in remission from depression (score of less than 12 on the Montgomery–Asberg Depression Rating Scale for at least two months). A total of 60 patients (48 were taking antidepressants) were evaluated using the Cambridge Neuropsychological Test Automated Battery, which includes tests of episodic memory, working memory, planning, and attention. One week after baseline evaluation of cognitive function, patients were randomized to receive either a single dose of modafinil (200 mg) or placebo, followed by another round of cognitive tests two hours after treatment.

The researchers found that the modafinil group significantly outperformed the placebo group on episodic memory and working memory tests. There were no differences between the groups in regards to improvements in planning and attention.

Although none of the study participants reported significant adverse events during the testing or 24 hours after the study, two patients taking modafinil reported sleep disturbances on the night of the study session.

“Cognitive deficits in remitted depression have detrimental effects on life functioning and pose a risk for relapse,” the authors wrote. “Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.”

For related information, see the Psychiatric News article “Is Modafinil a ‘Smart’ Choice to Treat Cognitive Problems in Psychiatric Disorders?

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Tuesday, January 17, 2017

Federal Confidentiality Rule Updated Regarding Substance Use Treatment


Federal regulations regarding the confidentiality of patient records on treatment for alcohol and other substance use disorders have been updated to account for the evolution of integrated care and other changes. The update appears in the form of a final rule that will be published tomorrow in the Federal Register

The rule “will further enhance health services research, integrated treatment, quality assurance, and health information exchange activities while at the same time safeguarding the essential privacy rights of people seeking treatment for substance use disorders,” said Kana Enomoto, deputy assistant secretary of the Department of Health and Human Services. She oversees the Substance Abuse and Mental Health Services Administration (SAMHSA). 

The previous regulations governing the confidentiality of substance use disorder records (referred to as "42 CFR Part 2”) were promulgated in 1975 to protect the confidentiality of patients receiving services for alcohol and other substance use disorders through programs that receive federal assistance. In February 2016, SAMHSA issued a notice of proposed rulemaking intended to adjust the regulations to reflect changes in the health care delivery system—especially the development of integrated care networks that depend on shared information—and permit appropriate research and data exchange activities.

Major provisions in the final rule include the following:
  • SAMHSA will allow any lawful holder of patient identifying information to disclose Part 2 patient identifying information to qualified personnel for purposes of conducting scientific research if the researcher meets certain regulatory requirements. SAMHSA also permits data linkages to enable researchers to link to datasets from data repositories holding Part 2 data if certain regulatory requirements are met. These will enable more needed research on substance use disorders.
  • SAMHSA will allow a patient to consent to disclosing their information using a general designation to individuals and/or entities (such as “my treating providers”) in certain circumstances. This change is intended to allow patients to benefit from integrated health care systems while retaining patient choice, confidentiality, and privacy; patients do not have to agree to such disclosures.
  • SAMHSA has added a requirement allowing patients who have agreed to the general disclosure designation the option of receiving a list of entities to whom their information has been disclosed.
  • SAMHSA has made changes that outline the audit or evaluation procedures necessary to meet the requirements of a CMS-regulated accountable care organization or similar CMS-regulated organizations. This change will ensure CMS-regulated entities can perform necessary audit and evaluations activities, including financial and quality assurance functions critical to accountable care organizations and other health care organizations.
  • The final rule addresses both paper and electronic documentation.
APA staff are analyzing the final rule. A report on the final rule and APA’s analysis will appear in a future issue of Psychiatric News. For information about confidentiality in mental health treatment, see the Psychiatric News article “Confidentiality: When Does It Give Way to Other Ethical Imperatives?

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Friday, January 13, 2017

Antidepressants May Increase Risk of Hip Fractures in Older Adults


Older adults taking antidepressants—particularly those with Alzheimer’s disease (AD)—appear to be at a greater risk of hip fracture than older adults not taking the medications, according to a report in the International Journal of Geriatric Psychiatry.

“Antidepressant use is associated with an increased risk of incident hip fracture among older persons with and without AD,” the study authors wrote. “Thus, if the antidepressant treatment is necessary, other risk factors for falling should be carefully considered.”

For the study, researchers from the University of Eastern Finland compared the health outcomes of 50,491 community-dwelling adults who were diagnosed with AD (mean age 80) and 100,982 age- and sex-matched controls without an AD diagnosis documented in national registers over a four-year period.

A total of 22.4% of the people with AD and 9.9% of persons without AD started taking antidepressants during the study period. (The most frequently initiated antidepressants included selective serotonin reuptake inhibitors, mirtazapine, and selective noradrenaline reuptake inhibitors.) 

During antidepressant use, the age-adjusted rate of hip fractures per 100 person-years was 3.01 among persons with AD and 2.28 among persons without AD. Antidepressant use was associated with an increased risk of hip fracture among persons with and without AD (adjusted hazard ratio [HR]=1.61; HR=2.71, respectively) compared with nonuse. This increased risk remained even after adjusting for use of antipsychotics, benzodiazepines, and other psychotropic drugs during the follow-up period.

“In our study, the adjusted hazard ratio was higher among persons without AD than in persons with AD. However, we found age-adjusted event rate for hip fracture per 100 person-years during antidepressant use was higher among persons with AD compared with persons without AD, which indicates the vulnerability of persons with AD.”

Additional analysis revealed that the risk of hip fracture was highest at the beginning of antidepressant use (1 to 30 days) in people with AD and without AD (HR=3.30; HR=3.92, respectively), but remained throughout the follow-up.

For related information, see the Psychiatric Services article “Antidepressant Prescribing in Primary Care to Older Adults Without Major Depression.” 

(Image: iStock/Barcin)

Thursday, January 12, 2017

Activity in Amygdala May Predict Risk of Later Cardiovascular Events


Higher emotional stress as measured by resting activity of the amygdala is associated with greater risk of subsequent cardiovascular disease events, according to a study published yesterday in The Lancet. The findings “provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease,” the authors stated.

Researchers examined data originally derived from cancer screening imaging studies of 293 patients to analyze amygdalar and bone-marrow activity, as well as arterial inflammation, reported lead author Ahmed Tawakol, M.D., an associate professor of medicine at Massachusetts General Hospital and Harvard Medical School.

During the median follow-up at 3.7 years, 22 patients reported having experienced a cardiovascular disease event—including heart attacks, strokes, angina, or other events. Each increase of one standard deviation in resting amygdalar activity predicted a 1.6 increased risk of a cardiovascular event. The results were significant even after adjustment for established cardiovascular risk factors.

Greater amygdalar activity was also associated with increased bone marrow activity, which the authors said led to increased arterial inflammation followed by cardiovascular disease events.

“[T]he brain’s salience network, bone marrow, and arterial inflammation together form an axis that could accelerate the development of cardiovascular disease,” concluded Tawakol and colleagues. “Furthermore, our findings raise the possibility that efforts to attenuate psychosocial stress could produce benefits that extend beyond an improved sense of psychological wellbeing, and could beneficially impact the atherosclerotic milieu.”

For more in Psychiatric News about the connection between heart disease and psychiatric illness, see “Can Collaborative Care Really Help Patients With Depression and Diabetes or Heart Disease.”

(Image: iStock/Ugreen)

Wednesday, January 11, 2017

Metabolic Changes in Schizophrenia May Predate Antipsychotic Use


By the time a person with schizophrenia presents at the onset of the illness, he or she may already be experiencing glucose dysregulation—increasing the risk of type 2 diabetes, a meta-analysis published today in JAMA Psychiatry reports. The findings highlight the importance of prescribing antipsychotics at a dose that limits the metabolic impact and educating patients about diet, exercise, and diabetic screening as early as possible after diagnosis.

While rates of type 2 diabetes are known to be two to three times higher in patients with schizophrenia than the general population, it was previously unknown whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term antipsychotic treatment. 

Oliver D. Howes, Ph.D., of the Imperial College London and colleagues conducted a systematic review of case-control studies reporting on fasting plasma glucose levels, fasting insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in individuals with first-episode schizophrenia who had minimal (≤2 weeks of antipsychotic treatment) or no exposure to antipsychotics. A total of 16 case-control studies were included in the analysis, including 731 patients and 614 controls. Fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, and insulin resistance were all significantly elevated in patients compared with controls, but HbA1c levels were not altered in patients compared with controls. 

The findings “indicate that individuals with schizophrenia present at the onset of illness with an already vulnerable phenotype for the development of type 2 diabetes,” the authors wrote. “Given that several antipsychotic drugs may worsen glucose regulation, there is thus a responsibility placed on the treating clinician to select an appropriate antipsychotic at an appropriate dose so as to limit the metabolic impact of treatment. Furthermore, the association between schizophrenia and glucose dysregulation suggests that patients should be educated regarding diet and physical exercise, as well as diabetic screening, and offered early lifestyle and pharmacologic interventions to combat the risk of progression to type 2 diabetes.”

For related information, see the Psychiatric News article “Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth” and the Psychiatric Services article “Health Promotion for Young Adults With Serious Mental Illness.”

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Tuesday, January 10, 2017

AJP Recognized for Outstanding Publication of Research That Informs Clinical Practice


Two prestigious institutions have recognized the American Journal of Psychiatry (AJP) for publication of outstanding research that informs and improves clinicians’ practice of psychiatry by enhancing assessment of patients or improving treatment options.

New England Journal of Medicine (NEJM) Journal Watch Psychiatry and the Brain and Behavior Research Foundation have each recognized its top 10 choices for research studies published in 2016. Two AJP articles were selected by NEJM Journal Watch Psychiatry, and three were selected by the Brain and Behavior Research Foundation. For both lists, AJP had the most number of listed publications.

“Providing reliable, up-to-date information for clinicians and their patients is the most important role of the American Journal of Psychiatry,” said AJP Editor Robert Freedman, M.D. “Therefore, the Editorial Board, our authors, and I take special pride in receiving top recognition this year from both NEJM Journal Watch Psychiatry and the Brain and Behavior Research Foundation for bringing our readers the highest quality information that can guide their practice now and in the future.”

These are the two reports selected by NEJM Journal Watch Psychiatry:

The Brain and Behavior Research Foundation selected these reports:

More information about these studies will appear in a future issue of Psychiatric News.


(Image: American Journal of Psychiatry)

Monday, January 9, 2017

Patients With Depression, Panic Disorder May Experience More Side Effects on Antidepressants


Patients with chronic depression and panic disorder appear to experience more side effects from antidepressants than those without panic disorder, according to a study in the Journal of Clinical Psychiatry.

“These results have clinical importance, as side effects vary in their tolerability, need for clinical management, and effects on attrition and outcome,” Stewart Shankman, Ph.D., of the University of Illinois at Chicago and colleagues wrote. “Thus, ability to predict which side effects will more likely occur matters for adequate pharmacological management.”

The researchers analyzed data collected as part of the Research Evaluating the Value of Augmenting Medication with Psychotherapy (REVAMP) trial, during which patients with chronic depression were openly assigned to antidepressants for 12 weeks. Every two weeks, patients were asked to evaluate antidepressant side effects using the Patient-Rated Inventory of Side Effects (PRISE) and the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER); depressive symptoms were also evaluated every two weeks, using the Hamilton Depression Rating Scale (HDRS).  

For the current study, Shankman and colleagues examined the associations between comorbid panic disorder, social phobia, and generalized anxiety disorder (GAD) and patient reports of side effects in eight categories: gastrointestinal, cardiovascular, dermatologic, neurologic, eye/ear, genitourinary, sleep, and sexual functioning. Of the 808 patients in the study, 85 had a lifetime diagnosis of panic disorder, 123 had a lifetime diagnosis of social phobia, and 85 had a lifetime diagnosis of GAD; 711 patients (88%) reported at least one medication side effect over the course of the 12-week trial. 

The researchers found that a diagnosis of comorbid panic disorder was positively associated with self-reported gastrointestinal, cardiovascular, neurologic, and genitourinary medication side effects—an association that was not seen in patients with GAD and social phobia. Additional analysis revealed that panic disorder significantly moderated the association between the frequency and severity of side effects and the course of depressive symptoms.

“That side effects and depressive symptoms were more strongly correlated for patients with panic disorder than for those without has important clinical implications,” the authors wrote. “Clinicians treating chronically depressed individuals should pay particular attention to gastrointestinal, cardiac, neurological, and genitourinary side effects reported by patients with comorbid panic disorder and perhaps adjust the treatment accordingly. [C]linicians may want to consider treating these patients’ panic disorder (or at least heightened interoceptive awareness) concurrent with the antidepressant treatment.

For related information, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don’t Respond.” 

(Image: iStock/shironosov)

Friday, January 6, 2017

Parental Obesity May Increase Children’s Risk of Developmental Delays


Both maternal and paternal obesity may increase a child’s risk of motor and social delays, suggests a study published this week in Pediatrics. The findings emphasize the importance of gathering information about families when screening child development, the authors wrote.

Edwina Yeung, Ph.D., of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and colleagues reviewed data from the Upstate KIDS Study, which recruited 5,034 women in New York State outside New York City about four months after giving birth.

Parents completed the Ages and Stages Questionnaire (ASQ) when their children were four, eight, 12, 18, 24, 30, and 36 months. (The ASQ screens for delays in five developmental domains: fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Mothers also completed a questionnaire about health status and lifestyle, which included questions regarding both parents’ height and weight, maternal weight prior to pregnancy, and gestational weight gain.

Compared with normal/underweight mothers (BMI <25), children of obese mothers (BMI ≥30) were 67% more likely to fail the test’s fine motor domain. Children of obese fathers were 75% more likely to fail the test’s personal-social domain—an indicator of how well they were able to relate to and interact with others by age 3. Children of two parents with class II/III obesity (BMI ≥35) had higher odds of failing multiple domains (fine motor, personal-social, and problem solving) compared with children of normal/underweight parents.

“[The] findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development,” Yeung and colleagues wrote.

While more research is needed to understand the relationship between parental obesity and children’s development, the authors noted that some studies suggest obesity-induced maternal inflammation or epigenetic alterations to sperm may alter offspring development.

“Approximately 1 in 5 pregnant women in the United States enter into pregnancy with a BMI ≥30,” the authors wrote. “Given that the prevalence of obesity is approximately double in the United States as in Europe, and that class II/III obesity (BMI ≥35) in both parents may be most concerning, the relevance of findings to a U.S. population is important.” 

For related information, see the Psychiatric News article “Meta-Analysis Finds Association Between Obesity and ADHD in Adults, Children.”

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Thursday, January 5, 2017

Study Suggests Incidence of First-Onset Psychosis May Exceed Prior Estimates


A detailed review of electronic health records from five large health care systems in the United States suggests that the incidence of first-onset psychotic symptoms may be higher than previous estimates, which were based on surveys or inpatient data. The findings, which revealed that nearly half of first diagnoses occurred among those aged 30 to 59, could have important implications for designing early intervention programs.

The study, published Tuesday in Psychiatric Services in Advance, suggests that the annual rate of first presentation of psychotic symptoms was approximately 86 per 100,000 among those aged 15 to 29 and 46 per 100,000 among those aged 30 to 59.

“Applied to the entire U.S. population, our incidence estimates would predict approximately 56,000 new first presentations of psychotic symptoms among those aged 15 to 29 and an additional 58,000 among those aged 30 to 59,” Gregory Simon, M.D., M.P.H., of Group Health Research Institute in Seattle and colleagues wrote.

The researchers analyzed electronic health records and insurance claims from January 2007 through December 2013 to identify all first-occurring diagnoses of psychotic symptoms among Group Health Cooperative and Kaiser Permanente (Colorado, Northern California, Southern California, and Pacific Northwest regions) health plan members aged 15 to 59. This included patients diagnosed with schizophrenia spectrum disorder, mood disorders with psychotic symptoms, and other psychotic disorders.

Exclusion of those with any diagnosis of dementia or neurodegenerative disease during the study period yielded a final sample of 37,843 putative cases over seven years. The researchers then selected a random sample of 1,500 cases (approximately 300 at each health care system) for a more detailed review to confirm the diagnosis and rule out prior diagnosis or treatment for psychotic disorder.

“Rates of chart review confirmation ranged from 84% among those aged 15 to 29 diagnosed in emergency department or inpatient mental health settings to 19% among those aged 30 to 59 diagnosed in general medical outpatient settings,” the authors wrote. “Only about one-third of first presentations occurred in emergency departments or inpatient mental health facilities, half occurred in outpatient mental health settings, and the remainder in primary care or other outpatient settings.”

They concluded, “Our findings have several important implications for the design of early intervention programs. First, the potential demand for early intervention services certainly exceeds the capacity of existing programs. Second, outreach or engagement efforts certainly cannot be limited to mental health inpatient facilities. Third, early intervention programs should consider the needs and preferences of [patients aged 30 to 59] who account for up to half of persons with new-onset psychotic symptoms.”

For related information, see the Psychiatric News article “Psychosocial Treatments Found Effective for Early Psychosis.”

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Wednesday, January 4, 2017

Alcohol Abuse Increases Risk of Multiple Cardiovascular Problems, Study Finds


Alcohol abuse increases the risk of heart problems to a similar degree as well-established cardiovascular risk factors such as hypertension and obesity, reports a study published Monday in the Journal of the American College of Cardiology. The study authors said that the findings suggest that efforts to mitigate alcohol abuse could lead to meaningful reductions of cardiovascular disease.

Researchers led by Gregory Marcus, M.D., of the University of California, San Francisco, analyzed a database of nearly 15 million California residents (aged 21 and older) who received ambulatory surgery, emergency care, or inpatient medical care in California between 2005 and 2009. The researchers then quantified the occurrences of alcohol abuse, cardiovascular outcomes, and other health data using International Classification of Diseases-9th Revision (ICD-9) and Current Procedural Terminology (CPT) codes given for each patient visit.

After adjusting for other potential risk factors, a diagnosis of alcohol abuse (identified in 268,084 patients, or 1.8%) was associated with a 2.14-fold increased risk of atrial fibrillation, a 1.45-fold increased risk of heart attack, and a 2.34-fold increased risk of congestive heart failure—magnitudes of risk that the authors noted are “similar to other well-established risk factors.”

They continued, “Although nearly all subgroups exhibited increased risk in the setting of alcohol abuse, those without a given risk factor for each outcome were disproportionately prone to enhanced cardiovascular risk.” However, while the relative risk of atrial fibrillation, heart attack, or heart failure rose significantly in this group, the absolute risk was still low. 

“The authors are to be commended for carefully differentiating between the relative risk and absolute risk of alcohol abuse—both individually and in combination with other risk factors—as such differences have clinical implications,” wrote Michael Criqui, M.D, M.P.H, and Isac Thomas, M.D., of the University of California, San Diego, in an accompanying editorial

Criqui and Thomas contrasted the findings by Marcus and colleagues with other research suggesting the health benefits of alcohol. Such studies, according to Criqui and Thomas, have tended to recruit more health-conscious participants and exclude heavy drinkers, so the results may be confounded by other lifestyle factors such as exercise and healthy eating.

“The current study likely presents a more valid picture of heavy drinking outcomes,” they wrote.

For related information, see the Psychiatric News article “Surgeon General Offers Next Steps for Tackling Substance Use.” 

(Alexey Lysenko/shutterstock)

Tuesday, January 3, 2017

State Supreme Court Ruling Expands 'Tarasoff' Duty for Washington State Clinicians


A Washington state Supreme Court decision appears to significantly broaden the duty that psychiatrists and other mental health professionals in that state have to protect and warn potential victims of violence by a patient under their care.

In Volk v. De Meerleer, the Washington state Supreme Court expanded the so-called Tarasoff standard regarding a mental health professional’s duty to protect and warn a third party of possible violence, asserting that the duty extends to any possible victim—even one that has not been specifically identified by the patient.

The ruling applies only to clinicians in Washington state. Although other states could conceivably adopt a similar standard, the ruling does not establish a legal precedent outside of Washington. (It was a 1976 case, Tarasoff v. Regents of the University of California, that established the principle that a mental health professional has the duty to protect a third party, specifically identified by a patient, that he or she may be potential victim of violence.)

Tarasoff has typically been interpreted to mean that the mental health provider owes a duty to the intended victim if the victim is identified or reasonably identifiable. But the new decision by the Washington state Supreme Court suggests that the duty is more expansive and that the provider may have an obligation to probe statements about violence to determine whether there is an intended victim and/or to infer intended victims from past sessions.

The decision creates a new category of “medical negligence,” rendering clinicians in Washington state potentially legally liable if it is determined that they should have known someone would be a victim of violence. APA signed on to an amicus brief with the Washington State Medical Society and six other groups saying that a lower court’s finding that mental health professionals owe a duty of care to the general public, not just to reasonably identifiable third parties, places an unfair burden on clinicians.   

APA CEO and Medical Director Saul Levin, M.D., M.P.A., said the ruling is a troubling one. “The court’s ruling in Volk v. De Meerleer places clinicians in Washington state in a difficult position and could have detrimental effects on the patient-psychiatrist relationship,” he said. “To the extent that a similar standard of liability could be adopted in other states, it should be of concern to psychiatrists and mental health professionals everywhere. APA will continue to follow developments in Washington state and continue to advocate for a fair and rational approach to Tarasoff duties.”

APA President Maria A. Oquendo, M.D., Ph.D., echoed those remarks. “Holding mental health professionals liable to third-party victims who were not  identifiable as targets of actual threats places an unreasonable burden on mental health professionals,” she said. “This decision marks a significant departure from previous case law concerning Tarasoff duties. Leaving it to a jury to determine whether a mental health provider ‘should have known’ that a patient would be dangerous has a real potential to interfere with treatment of mental health patients.”

Marvin Swartz, M.D., chair of the APA Committee on Judicial Action, told Psychiatric News that the decision potentially undermines the traditional understanding of physician liability. “Expanding physician liability to a new doctrine of ‘medical negligence’ suggests that courts and juries might begin to adopt a liability standard akin to strict product liability rather than the established standards of medical malpractice,” he said. “The likely result would be a serious undermining of the physician/patient relationship.”

Look for further coverage of the court’s decision in a future issue of Psychiatric News.

For more information on the Tarasoff decision, see the Psychiatric News article “What Is My Duty to Warn?

(Image: iStock/DenisLarkin)

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