Monday, December 11, 2017

Pregnant Women With Dissociative Subtype of PTSD Have Higher Levels of Cortisol, Study Finds

Pregnant women with a severe subtype of posttraumatic stress disorder (PTSD) appear to have higher levels of the stress hormone cortisol than other pregnant women with a history of trauma, reports a study in the Journal of Obstetric, Gynecological, and Neonatal Nursing. Such high levels of cortisol may contribute to adverse health conditions in the next generation, according to the study authors.

“Exposure to early relational trauma that predisposes a person to dissociation and PTSD may affect that individual’s short- and long-term cortisol patterns,” wrote Julia S. Seng, Ph.D., of the University of Michigan and colleagues. Previous studies suggest that elevated cortisol levels are a risk factor for preterm birth, affecting the onset of labor and inflammatory processes.

A diagnosis of PTSD may include a dissociative subtype (PTSD-D) characterized by altered perception of oneself and the world. PTSD-D is associated with a greater number of lifetime trauma exposures, including a history of childhood maltreatment.

The study by Seng and colleagues involved 395 women expecting their first child who were divided into four groups: those without trauma, those with a trauma but no PTSD, those with lifetime PTSD, and those with PTSD-D (presence of depersonalization and/or derealization consistent with the DSM-5 dissociative subtype definition). The researchers analyzed saliva cortisol specimens collected by these women at three different times on a single day during the first half of their pregnancy. A subsample of 111 women, including women from each of the four cohorts, provided three salivary cortisol specimens per day, 12 times, from early pregnancy to six weeks postpartum for longitudinal data (This sample included 34 women without trauma, 38 with trauma but no PTSD, 31 with PTSD only, and eight with PTSD-D).

In early pregnancy (gestational week 8), the cortisol levels of participants in the PTSD-D group were two times greater in the morning, eight times greater in the afternoon, and 10 times greater at bedtime than the cortisol levels of participants in the non-exposed control group. In late pregnancy (gestational week 32), participants in the PTSD-D group had cortisol levels that were less than two times greater in the morning and 1.5 times greater levels in the afternoon and at bedtime compared with participants in the non-exposed control group. The difference between the PTSD-D and the other groups was most apparent in early pregnancy, which is a critical period for fetal development, noted the authors.

“Although some women with histories of childhood maltreatment are resilient or recovered by the time they become pregnant, these biological findings indicate that some are very adversely affected psychologically and very stressed during the childbearing year,” the authors wrote. “We can screen and apply a stepped approach to maternity care that includes case-finding and interventions for women with PTSD, posttraumatic depression, and PTSD-D.”

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

(Image: pio3/Shutterstock)

Friday, December 8, 2017

APA Paper Describes How Psychiatrists Can Improve Health of SMI Patients

Psychiatrists should routinely screen patients with serious mental illness (SMI) for common medical conditions, counsel them on lifestyle modifications to reduce cardiovascular risk factors, and coordinate with their primary care physicians to narrow the longevity gap between this group and the general population. These were some of the conclusions in a white paper that APA issued yesterday at a Capitol Hill briefing.

More than a decade has passed since researchers found that people with SMI treated in the public mental health system are dying on average 25 years earlier than the general population. “The majority of these deaths are due to untreated medical issues,” said Saul Levin M.D., M.P.A., APA CEO and medical director. “However, little progress has been made in rectifying this disparity.”

While patients with SMI often suffer from economic disadvantage and chronic stress caused by their illness, modifiable risk factors play a role as well that psychiatrists can readily address. Patients with SMI are more likely than the general population to use tobacco or other substances, have a poor diet, lead a sedentary lifestyle, and not comply with treatment regimens. These factors, coupled with the propensity for psychotropic medications to cause obesity and metabolic disorders, all contribute to the early mortality of patients with SMI. “But treatment is possible, and treatment does work,” Levin said.

Medical professionals’ bias against and stereotyping of SMI patients, particularly in the emergency department (ED), can also imperil the lives of these patients, said Glenda Wrenn, M.D. (above), director of the Kennedy-Satcher Center for Mental Health Equity at Morehouse School of Medicine in Atlanta. In fact, ED physicians list dealing with psychiatric patients as their “chief complaint” about doing their job, she said. She has seen cases in which patients with SMI died of delirium tremens because ED physicians failed to catch acute alcohol withdrawal.

Medical training for psychiatrists is often limited to medical school and a few months of internship, pointed out Benjamin G. Druss, M.D., the Rosalynn Carter Chair in Mental Health at Emory University. To keep their skills up to date, training in outpatient medical care should be provided to practicing psychiatrists in continuing medical education programs and cross-training opportunities with other medical service providers.

Ultimately, the white paper calls for more research on which models of care would best lead to the improvement of SMI patients’ physical health as well as determine the optimal role of psychiatrists in these models.

(Image: David Hathcox)

Thursday, December 7, 2017

ABPN to Pilot New Test Format as Alternative to 10-Year Proctored MOC Exam

The American Board of Psychiatry and Neurology (ABPN) is piloting a new open-book, journal article–based assessment beginning in 2019 as an alternative to the proctored 10-year Maintenance of Certification (MOC) examination.

Eligible diplomates who choose to participate in this pilot program will be required to read and answer questions on between 30 and 40 journal articles. Diplomates may choose from a library of articles that have been selected for the test by the ABPN Pilot Project Test Writing Committees. The pilot project will run for three years, from 2019-2021. If approved by the American Board of Medical Specialties (ABMS), the ABPN plans to transition diplomates into this program in 2022 as a permanent alternative to the secure MOC examination. Staff at ABPN say emailed invitations to the new testing option will be delivered next week.

Diplomates who are eligible to participate in the pilot program are those who are currently certified and who fall into one of two categories: those who have earned ABPN certification or who passed the MOC examination in the years 2012, 2013, or 2014 in psychiatry, child and adolescent psychiatry, neurology, or child neurology; or those whose certificate is expiring in 2019, 2020, or 2021 in psychiatry, child and adolescent psychiatry, neurology, or child neurology.

APA leaders said that the article-based, open-book test option is an important step in making MOC more flexible.

“Requirements around Maintenance of Certification are among the most prominent concerns of our members, and many have been asking for an alternative to the 10-year, secure, proctored exam,” APA President Anita Everett, M.D., told Psychiatric News. “APA has been advocating for something similar to the open-book journal article–based assessment, and we hope it provides an attractive option for members to consider.”

APA CEO and Medical Director Saul Levin, M.D., said the new program “provides more flexibility in terms of diplomates being able to select articles that are relevant to their own practice. It allows diplomates to read the articles and complete the test at their own pace.”

More information about the new test option will appear in an upcoming edition of Psychiatric News. Information on the program is also available on the ABPN website.

(Image: iStock/DNY59)

Wednesday, December 6, 2017

Adjunctive Ketamine Appears to Reduce Suicidal Thoughts in Depressed Patients for Up to Six Weeks

A single adjunctive infusion of ketamine appears to reduce suicidal thoughts in depressed patients within 24 hours, according to a study published yesterday in AJP in Advance. This improvement was maintained for six weeks with standard, optimized pharmacotherapy.

While previous studies have suggested ketamine rapidly reduces suicidal ideation in some patients, whether similar effects would be seen in patients with major depression and high levels of suicidal ideation was less clear.

Researchers from Columbia University Medical Center and the New York State Psychiatric Institute randomly assigned 80 adults with major depressive disorder and suicidal ideation to receive ketamine or midazolam infusion. At baseline, 54% of the sample was taking antidepressant medication.

The researchers assessed the study participants’ suicidal ideation at the start of the trial using the clinician-rated Scale for Suicidal Ideation (SSI). The SSI consists of 19 items, including severity of wish to die, passive and active suicide attempts, and duration and frequency of ideation, which can be used to monitor a patient's response to interventions. This assessment was repeated 24 hours before infusion with ketamine or midazolam, 230 minutes after infusion, 24 hours after infusion, and at weeks one to six after infusion. Patients were also asked about symptoms of depression and anxiety before and after the infusion, as well as adverse effects following the infusion and again at six-week follow-up.

Within 24 hours of patients’ having received intravenous ketamine (0.5 mg/kg in 100 mL saline) or midazolam (0.02 mg/kg in 100 mL saline) infused over 40 minutes, patients in the ketamine group experienced a greater reduction in SSI score than that of the midazolam group. The proportion of patients who experienced a reduction ≥50% in their SSI score 24 hours after receiving an infusion was 55% for the ketamine group and 30% for the midazolam group. The ketamine group also experienced greater reductions in overall mood disturbance, depression, and fatigue, as measured by the Profile of Mood States, within 24 hours compared with the midazolam group.

“Longitudinal analysis of the uncontrolled six-week follow-up showed that clinical improvement after randomized and open ketamine treatment was generally maintained through six weeks of open, optimized clinical follow-up treatment with respect to SSI score and depression ratings,” Michael F. Grunebaum, M.D., and colleagues wrote.

Patients in the ketamine group experienced an increase in blood pressure and dissociative symptoms compared with patients in the midazolam group, but these adverse effects typically resolved within minutes to hours following the infusion.

“Given concerns about ketamine’s one- to two-week antidepressant effect in previous studies, it is notable that the improvement in suicidal ideation in this trial was largely maintained through the six-week follow-up ratings,” the researchers wrote. “This may be partly explained by the fact that patients continued prior psychotropic medication, which was optimized after completion of day 1 postinfusion ratings.”

For related information, see the Psychiatric News article “Analysis Finds Single-Dose Ketamine Effective for Suicidal Ideation.”

(Image: iStock/agrobacter)

Tuesday, December 5, 2017

New Geriatric Cognition Chart May Improve Dementia Monitoring

Researchers at Laval University in Quebec and colleagues have devised an assessment chart called QuoCo (for cognitive quotient) to track patient cognition, offering a new method they say can help identify dementia during the earliest stages. The study was published yesterday in the Canadian Medical Association Journal.

“Similar to the ‘growth charts’ that are used in pediatrics, cognitive charts allow physicians to position any patient based on age, education, and Mini-Mental State Examination [MMSE] scores, and simply track the longitudinal profile of cognitive decline over time,” wrote lead study author Patrick Bernier, M.D., Ph.D., and colleagues. Such a chart “could prompt earlier intervention for an older adult who ‘fell off’ the curve,” the authors noted.

The MMSE is commonly used to screen for dementia, but there is no consensus on how best to determine whether changes in MMSE scores over time reflect age-associated cognitive decline or represent mild cognitive impairment or dementia. Also, previous studies show MMSE cut-off scores are less reliable for some populations, particularly for older adults with less formal education.

Bernier and colleagues analyzed data from a longitudinal study of older adults known as the Canadian Study of Health and Aging. They assessed 7,569 participants aged 65 years or older who completed an MMSE at study baseline, and then 5 and 10 years later.

By comparing score results of the 6,411 participants who remained cognitively healthy during the follow-up with the 1,158 who developed dementia, while controlling for age and education, the investigators developed QuoCo scores. Similar to charts used to monitor infant growth, the researchers developed a chart that reflected optimal rates of gradual cognitive decline with age, divided into five broad percentile zones. Any patient who dropped by more than one percentile zone on the QuoCo following their initial visit was classified as having dementia.

Bernier and colleagues found that the model could distinguish healthy participants from those with dementia with a specificity of 89% and a sensitivity of 80%. The QuoCo was about 12% better overall than only using an MMSE score of 24 or less as a dementia cutoff; however, while using the cognitive charts improved the classification of patients with dementia, it also increased the misclassification of some patients with normal cognition.

To read more on this topic, see the Psychiatric News article “Dual-Task Gait Testing Identifies MCI Patients Likely to Develop Dementia.”

(Image: iStock/monkeybusinessimages)

Monday, December 4, 2017

Long-Term SSRI Treatment May Delay Progression From Mild Cognitive Impairment to Alzheimer’s Dementia

Long-term treatment with selective serotonin reuptake inhibitors (SSRIs) may benefit elderly patients with mild cognitive impairment (MCI) and a history of depression, even after depressive symptoms have resolved, suggested a study published in AJP in Advance.

In patients with MCI and a history of depression, long-term treatment with SSRIs (for more than four years) was associated with a delayed progression to Alzheimer’s dementia by about three years, compared with those who used SSRIs only short term or who had no treatment.

Delaying the progression from MCI to Alzheimer’s dementia would not only reduce the prevalence of Alzheimer’s disease, but also cut health insurance costs, wrote Claudia Bartels, Ph.D., of the University of Medical Center Gottingen, in Germany, and colleagues.

Bartels and colleagues analyzed data on 755 nondepressed adults aged 55 to 90 who were culled from the multicenter Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were categorized at baseline as cognitively normal control subjects, patients with MCI, and patients with Alzheimer’s dementia and were comprehensively reassessed every six months or annually for progression from cognitively normal to MCI or Alzheimer’s dementia, or from MCI to Alzheimer’s dementia.

Of the 755 participants in the analysis, 532 were allocated at baseline to the “no history of depression–no antidepressants” group and 223 to the “history of depression” group. Of the latter group, 60 were untreated (prior depression–no antidepressants), 116 had received SSRIs (prior depression–SSRI), and 47 had received antidepressants other than SSRIs (prior depression–other antidepressants).

Statistical analysis revealed “a significantly decreased probability of conversion to Alzheimer’s dementia in MCI patients with a history of depression and long-term SSRI treatment [>1,610 days] compared with all other groups,” the authors reported. “The risk of conversion was increased in MCI patients with a history of depression and other antidepressant treatment compared with the no prior depression–no antidepressants group.” After three years of observation, however, the advantage of long-term SSRI treatment in previously depressed patients “dissolved,” researchers noted, and all groups had similar rates of progression from MCI to Alzheimer’s dementia.

The authors concluded, “Pending validation in an intervention trial, the data produced in this study may have important implications for clinical practice. … A prospective study to confirm SSRI effects on MCI progression is now warranted, as an SSRI-mediated delay may contribute to an overall lower prevalence of Alzheimer’s dementia, with a major impact on affected individuals, caregivers, public health, and health costs.”

(Image: iStock/sturti)

Friday, December 1, 2017

FDA Approves First Once-Monthly Injectable Buprenorphine for Opioid Use Disorder

The Food and Drug Administration (FDA) has approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adults who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. Sublocade is indicated for patients who have been on a stable dose of buprenorphine treatment for a minimum of seven days and is meant to be used as part of a complete treatment program that includes counseling and psychosocial support.

“Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine,” the FDA stated in a press release.

The FDA approval of Sublocade was based in part on the results of two clinical studies of 848 adults who had a diagnosis of moderate-to-severe OUD and began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval, according to Indivdor Inc., manufacturer of the medication.

In a 24-week phase 3 trial, researchers randomized patients to one of the following three regimens: six once-monthly Sublocade 300 mg doses; two once-monthly Sublocade 300 mg doses followed by four once-monthly 100 mg doses; or six once-monthly injections of placebo. According to Indivor, both dosage regimens of Sublocade were shown to be superior to placebo in achieving more illicit opioid-free weeks.

“The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose-stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer interdose interval than once monthly, and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose),” the agency’s press release stated.

The most common side effects of Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site, and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents under 17 years of age or adults over age of 65.

Sublocade features a boxed warning that notes the dangers of administering the drug intravenously instead of subcutaneously: “Sublocade forms a solid mass upon contact with body fluids and may cause occlusion, local tissue damage, and thrombo-embolic events, including threatening pulmonary emboli, if administered intravenously.”

The medication must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy to ensure that the product is not distributed directly to patients, the FDA noted.


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