Tuesday, July 25, 2017

High Proportion of Deceased Football Players Found to Have CTE


A postmortem analysis of the brains of 202 former football players from the high-school to the professional level has revealed that 87% of these athletes had neuropathological signs of chronic traumatic encephalopathy (CTE)—a progressive neurodegenerative disorder associated with repetitive head trauma. Moreover, as reported today in JAMA, all but one of the brains of the former National Football League (NFL) players showed neuropathological signs of the disease.

“Nearly all of the former NFL players in this study had CTE pathology, and this pathology was frequently severe,” wrote senior author Ann McKee, M.D., of the Boston University (BU) CTE Center and colleagues. “These findings suggest that CTE may be related to prior participation in football and that a high level of play may be related to substantial disease burden.” 

McKee and colleagues evaluated samples that were donated to a brain bank established in collaboration between the BU School of Medicine, the Boston and Bedford Veterans Administration Systems, and Concussion Legacy Foundation. A neuropathological diagnosis was made using criteria for CTE defined by an expert panel organized by the National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering in 2015. Retrospective clinical evaluations were performed using online surveys and structured and semi-structured postmortem telephone interviews between researchers and next of kin.

CTE was identified in 177 of 202 samples, including 3 of 14 high school players (21%); 48 of 53 college players (91%); 9 of 14 semiprofessional players (64%); 7 of 8 Canadian Football League players (88%); and 110 of 111 NFL players (99%). 

The severity of CTE correlated with the highest level of play, with all three former high school players having mild CTE pathology whereas 56% of college players, 56% of semiprofessional players, and 86% of professional players having severe pathology. Based on retrospective clinical evaluations, 33% of players with mild CTE had signs of dementia, compared with 85% of players with severe CTE. Players with severe CTE also had a higher occurrence of a comorbid neurological disorder such as Alzheimer’s, Lewy body disease, and frontotemporal degeneration.

Unlike the dementia differences, behavioral, mood, and/or cognitive symptoms were extremely common in players with CTE regardless of severity. Also, over 40% of the former players first sought clinical help for mood or behavioral problems. “Behavior or mood symptoms may be the initial presentation for a subset of individuals with CTE, or alternatively, CTE pathology may lower the threshold for psychiatric manifestations in susceptible individuals,” the authors wrote.  

McKee and colleagues cautioned that the high frequency of CTE in this study could be exaggerated, as the brain bank is oversampled with professional football players and increasing public awareness of CTE may have motivated players with symptoms of brain injury to donate to the brain bank. 

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences articles “Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination” and “Suicide and Chronic Traumatic Encephalopathy.”

(Image: iStock/fredrocko)

Monday, July 24, 2017

Expert Panel Publishes Comprehensive Guidelines for Treating PANS/PANDAS


An expert panel of clinicians and researchers has published comprehensive guidelines for treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS).

PANS/PANDAS is characterized by an unusually abrupt onset of obsessive-compulsive disorder (OCD) symptoms and/or severe eating restrictions in children, along with secondary behavioral, cognitive, and/or neurological symptoms. This syndrome is believed to result from a range of triggers, though studies have shown that autoimmune problems and/or neuroinflammation drive the illness in most cases.

Accordingly, the treatment guidelines, published in the Journal of Child and Adolescent Psychopharmacology, are divided into three clinical focus areas:
  1. Psychiatric and behavioral interventions to address obsessive-compulsive symptoms, eating restrictions, anxiety, irritability, and more.
  2. Immunomodulatory therapies that target the neuroinflammation and post-infectious autoimmunity commonly seen in PANS/PANDAS.
  3. Treatment and prevention of the streptococcal and other infections that underlie these neuropsychiatric conditions.
“While underlying infectious and inflammatory processes in PANS and PANDAS patients are treated, psychiatric and behavioral symptoms need simultaneous treatment to decrease suffering and improve adherence to therapeutic intervention,” Margo Thienemann, M.D., of Stanford University, Susan Swedo, M.D., of the National Institutes of Mental Health, and colleagues wrote. “Psychological, behavioral, and psychopharmacologic interventions tailored to each child's presentation can provide symptom improvement and improve functioning during both the acute and chronic stages of illness.”

Clinical evidence suggests that depression, anxiety, OCD, and other behavioral symptoms of PANS/PANDAS respond to the same medications used to treat these disorders in the general population. However, some reports also suggest that PANS/PANDAS patients may be more sensitive to adverse effects of psychotropic medications such as agitation or dystonia, the authors noted in the psychiatric guidelines (part I).

Therefore, clinicians are advised to initiate with dosages no more than one-quarter the normal amount and slowly titer upwards. Benzodiazepines are also considered first-line treatments for PANS/PANDAS as anxiety, agitation, aggression, and insomnia are common symptoms, but clinicians and parents should be aware of the risk of disinhibition following benzodiazepine treatment in pediatric patients.

For related information, see the Psychiatric News article “Experts at BIO Convention Discuss Link Between Infection, Psychiatric Disorders.”

(Image: ESB Professional/Shutterstock)

Friday, July 21, 2017

Psych News PsychoPharm Reports on Why FDA Took Steps To Encourage Removal of Opana ER From Market


When Endo Pharmaceuticals earlier this month announced that the company was pulling its opioid analgesic Opana ER (oxymorphone hydrochloride extended release) from the market, it marked the end of the road for a reformulated medication whose abuse by injection has been associated with multiple disease outbreaks.

“We are facing an opioid epidemic—a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Scott Gottlieb, M.D., said in a press release announcing the agency’s formal request in June that Endo stop selling the medication. The action by the FDA was “the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse,” the release stated.

While other opioids such as morphine and oxycodone are also abused, an article appearing today in Psychiatric News PsychoPharm describes how the Opana ER tablet is somewhat unusual: contributing to some of its deadly consequences are the inactive ingredients.

The older version of Opana ER tablet, which had been on the market from 2006 to 2011, was a simple formulation that released a small and steady amount of oxymorphone over 12 hours to maintain continuous pain relief. In 2012, after reports of people abusing the medication by crushing the tablet and snorting the powder, Endo replaced the original Opana ER tablet with a new formulation that contained a polymer known as polyethylene oxide (PEO) to make the tablet difficult to crush. If mixed with water, the tablet turns into a gel-like substance. The company had hoped to win the FDA’s “abuse-deterrent” label for this formulation, but the agency rejected the request, noting that it did not reach the standard for abuse deterrence.

Reformulated Opana ER deterred snorting, but individuals soon discovered that it was easier to “melt” and dissolve the tablet with heat. The liquid could be injected intravenously to produce the desired effect—a practice that led to more dangerous outcomes than snorting the tablets, Psychiatric News PsychoPharm reports. The article describes outbreaks of HIV and hepatitis C, as well as cases of a serious blood disorder known as thrombotic microangiopathy that can be traced back to injection abuse of Opana ER.

For more information on oxymorphone, the FDA’s action, and a list of 10 opioid analgesic products that have received the designation by the FDA as being “abuse deterrent,” see the full article here.

Today’s issue of Psychiatric News PsychoPharm also includes information on when to recommend SAMe for depression, findings that suggest imipramine may benefit patients with multiple somatic disorders, and more.

(Image: iStock/Mordolff)

Thursday, July 20, 2017

‘Willingness’ May Predict How Well Patients With Severe OCD Respond to ERP Therapy


Willingness to experience unpleasant and unwanted thoughts, emotions, and bodily sensation during an exposure appears to improve exposure therapy outcomes among patients with severe obsessive-compulsive disorder (OCD), according to an article published July 17 in Depression and Anxiety.

“Data indicated that individuals with higher willingness during ERP [exposure and response prevention] reported faster symptom reduction during residential treatment, even when controlling for length of stay, psychopharmacological intervention, depression, adherence, and rituals performed during ERP,” Adam M. Reid, Ph.D., of the OCD Institute for Children and Adolescents at McLean Hospital and colleagues wrote.

Reid and colleagues set out to explore why ERP—considered the gold-standard psychotherapeutic treatment for OCD—is not fully effective for more patients with OCD. ERP is considered effective for about 50% to 80% of adults with OCD.

Previous research by others on acceptance and commitment therapy suggested that willingness is a marker of acceptance and is associated with improved engagement in distressing tasks. Reid and colleagues decided this would be an important factor on which to focus for their ERP research.

For the current study, 288 adults seeking treatment at an intensive/residential treatment (IRT) program for OCD participated in 4 hours of ERP per day for six weeks. About 25% to 50% of the sessions were led by trained clinical residence counselors or practicum students, and the remainder were self-directed. During each coached exposure session, coaches asked patients to rate how willing they felt before and during the exposure, as well as how willing they would be to repeat the exposure in the future. Willingness was rated on a scale of 0 (not at all willing) to 100 (extremely willing). The 10-item Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used for assessing symptom severity.

Average Y-BOCS scores at baseline were 25.42, indicating that the average patient in the study had clinically severe OCD. After six weeks of ERP, OCD symptoms fell an average of 8.16 points on the Y-BOCS, resulting in an average reduction of 31% in symptoms. Higher willingness to engage in ERP was associated with more adherence, less ritualizing, and more habituation during ERP.

Reid and colleagues also asked patients to self-report their willingness to engage in ERP at three different time points: before ERP, immediately after, and for future exposures. Higher willingness at each time point was found to be associated with faster symptom reduction during six weeks of residential-level exposure therapy.

“Perhaps patients with higher willingness are more amenable to facing a higher number of novel stimuli and environments during exposure therapy,” the authors wrote. “[W]illingness may provide a clinical marker of exposure response that can be feasibly captured by clinicians in a naturalistic clinical setting.”

For related information, see the Psychiatric News article “Report Highlights Alternative Treatment Options for OCD.”

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Wednesday, July 19, 2017

Brain Imaging Offers Clues About PTSD Patients Most Likely to Benefit From Prolonged Exposure Therapy


Brain imaging may be able to predict patients with posttraumatic stress disorder (PTSD) who are most likely to benefit from the trauma-focused psychotherapy known as prolonged exposure, according to a study published yesterday in AJP in Advance.

Prolonged exposure—which helps patients confront trauma memories and real-life situations that provoke symptoms—is known to be an effective treatment for PTSD, but many patients fail to respond to this therapy. Senior author Amit Etkin, M.D., Ph.D., of Stanford University School of Medicine and colleagues used functional MRI (fMRI) to examine brain activity in 66 patients with PTSD before prolonged exposure to see if there were functional differences between the brains of patients who responded to prolonged exposure therapy and those who did not.

The patients underwent fMRI while resting and while carrying out tasks meant to elicit emotional response and regulation when presented with a series of happy, fearful, or neutral facial images and negative or neutral photographs. The patients were then randomly assigned to immediate prolonged exposure treatment (nine to 12 90-minute prolonged exposure sessions held once or twice a week) or a waiting-list condition. Four weeks after the final treatment session or comparable waiting period, all participants completed a posttreatment clinical assessment.

Patients who received prolonged exposure therapy demonstrated a greater reduction in PTSD symptom scores than those assigned to the waiting list. Those with greater baseline dorsal prefrontal activation and less left amygdala activation during emotion reactivity tests showed larger reductions in symptom scores after treatment, the authors reported. Similarly, individuals with greater baseline ventromedial prefrontal/ventral striatal activation during implicit regulation of emotional conflict demonstrated larger symptom reductions after treatment.

According to Etkin and colleagues, the findings suggest that “an individual’s capacity to benefit from exposure therapy is gated by [the] degree of spontaneous prefrontal control over amygdalar threat detection signals during incidental processing of a fear-conveying stimulus and the brain’s capacity to reduce interference from an emotional cue in the environment.” 

“This study provides a solid footing for understanding mechanisms so we can start working toward matching people to the treatment most likely to work for them and develop novel therapeutics for directly targeting brain therapy,” said Etkin. “By grounding psychotherapy in brain mechanisms, we can also hopefully decrease stigma, an invisible barrier to care that is so prevalent in psychiatric disorders and prevents people from getting the care that would benefit them.”

In an accompanying paper in AJP, Etkin and colleagues describe how imaging also revealed changes in the frontopolar cortex (the front-most portion of the prefrontal cortex) of PTSD patients who received prolonged exposure.

For related information, see the Psychiatric News article “Brain Scans May Indicate Optimal Treatment for Depression.”

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Tuesday, July 18, 2017

Digital Ads Offer Cost-Effective Strategy for Engaging Users About Early Psychosis


Using digital advertising is a successful and cost-effective strategy to engage individuals who are searching for mental health information online, reports a study published Monday in Psychiatric Services in Advance.

A team at the Zucker Hillside Hospital in Glen Oaks, N.Y., employed Google AdWords—clickable ads that appear when online searches match selected keywords—to raise awareness about early psychosis and encourage people to contact their local intervention clinic. 

“Although advertisers have long used the Internet to target consumers directly beyond the capabilities of traditional media, limited efforts have focused specifically on applying available technology to target and identify help-seeking individuals in real time and refer them to appropriate resources,” Michael Birnbaum, M.D., and colleagues wrote. 

Birnbaum and colleagues selected more than 2,000 keywords across 15 psychosis-related themes. General terms such as “psychosis,” as well as more specific terms such as “hearing voices” and “mind control,” were included to target both individuals searching for information for themselves and persons searching on behalf of a loved one. They next created 154 ads consisting of a headline related to the user’s search, description line, and call to action. The ads linked to a dedicated landing page that offered links to Northwell Health’s Early Treatment Program (ETP); an online form for submitting questions to ETP staff; and the Prodromal Questionnaire–Brief (PQ-B), an evidence-based screening tool that visitors to the page could use to assess psychosis risk. Google analytics were used to record Web site engagement. 

The digital campaign ran for 14 weeks and cost $1,427. During the campaign period, the early intervention ads appeared 191,313 times and received 4,350 clicks (2.3% click rate), resulting in an average cost of 33 cents per click. Once on the landing page, 44% (1,918) of users obtained psychosis-specific informational materials, 15% (671) completed an online psychosis self-screener, and 1% (57) contacted the ETP, which translates to $25 spent per desired outcome.

Compared with the industry average among health and medical campaigns, this project had favorable outcomes in terms of click rate (2.3% versus 1.8%), cost per click (33 cents versus $3.17) and cost per outcome ($25 versus $126.29), the authors reported.

“It is possible that the leap between searching for information online and making contact with a clinical team is too big for many individuals as an initial step,” Birnbaum and colleagues wrote. “Intermediate steps toward treatment in the form of digital engagement tools would also allow researchers to learn more about what users are seeking and why, as well as the barriers they face in considering treatment for psychosis.”

To read more about early psychosis intervention, see the Psychiatric News article “Early Identification of People With Psychosis Linked to Educating Outpatient Providers.”

(Image: iStock/izusek)

Monday, July 17, 2017

Members Urged to Contact Senators While McCain Recuperates


The Senate Republican health care reform bill, titled the Better Care Reconciliation Act (BCRA), appears to be on hold indefinitely until Sen. John McCain (R-Ariz.) returns to the Senate from surgery for a blood clot.

At press time, it was uncertain whether the bill would garner the necessary 50 votes for passage, even if McCain were available. In the meantime, however, APA continues to urge members to contact their Senators to voice opposition to the bill and use this delay to continue to voice their concerns. 

The BCRA, revised after an earlier version of the bill failed to make it to the Senate floor in June, retains some of the most problematic aspects of the original bill. These include deep cuts to Medicaid and the ability to waive the “essential health benefits” that must be covered in plans under the Affordable Care Act (ACA), including benefits for mental health and substance use disorders treatment.

Based on analysis by APA staff, the bill proposes to do the following:
  • Fundamentally alters the payment structure of the Medicaid program. Beginning in FY 2020, state Medicaid programs will be funded on a fixed per-beneficiary basis (that is, a per capita cap). 
  • Phases out Medicaid expansion made available to states under the ACA. States will no longer be able to expand eligibility for their Medicaid programs on January 1, 2020.
  • Establishes an optional block grant program called the Medicaid Flexibility Program.
  • Adds administrative costs and burdens to Medicaid programs. The BCRA requires states to reassess enrollees’ Medicaid eligibility once every six months. It would also give states the option of requiring nondisabled, nonelderly, and nonpregnant individuals to satisfy work requirements as a condition for eligibility.
Also under consideration is a controversial amendment to the bill proposed by Sen. Ted Cruz (R-Tex). The amendment would allow insurers to offer plans that do not comply with the ACA’s mandatory coverage provisions, including the requirement that plans cover certain “essential health benefits,” the prohibition against insurers increasing premiums for individuals with pre-existing conditions, and the requirement that plans offer a free annual preventative care visit to enrollees.

APA Department of Government Relations staff have prepared a detailed analysis of the bill as well as a side-by-comparison of all of the health reform proposals in play: the existing Affordable Care Act, the House-passed American Health Care Act, the initial version of BCRA from June, and the revised BCRA now pending in the Senate.

To make contacting your senator as easy as possible and voice your opinion, APA has established a special portal on the APA website that provides messaging and contact information specifically for your senators.

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Friday, July 14, 2017

APA Calls on Senate to Reject Latest Republican Health Care Reform Bill


APA is urging members to contact their U.S. senators and voice their opposition to the new Senate health care reform bill, released yesterday by Senate Majority Leader Mitch McConnell (R-Ky).

Senate Republicans released a revision of the Better Care Reconciliation Act (BCRA), the original version of which never made it to the Senate floor for a vote when it became clear that the bill would fall short of 50 votes. The revised BCRA was introduced after McConnell announced he was delaying the start of the August recess by two weeks (until August 14) to allow more time to address the legislation.

The new BCRA still includes provisions that are deeply problematic, especially for individuals with serious mental illness and substance use disorders. The bill retains the deep Medicaid cuts that were a feature of the original reform bill and permits the removal of the essential health benefits. Both are significant concerns to APA.

“Wordsmithing and throwing money at certain constituencies to gain more votes highlights a deeply flawed Senate proposal that is insufficient,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in a statement released yesterday. “The changed bill still rolls back access to care and allows for the removal of essential health benefits, such as treatment for mental illness and substance use disorders, that will affect millions of patients and their families—from the young to the elderly to the most vulnerable in all our communities.”

APA staff are continuing to analyze the bill. An updated cost estimate by the Congressional Budget Office is expected early next week, with Senate leadership planning a procedural vote on Tuesday or Wednesday to determine whether to proceed to debate on the bill.

APA will continue to actively engage the Senate and participate as part of a “Frontline Physician” coalition with five other groups (the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American College of Obstetricians & Gynecologists, and American Osteopathic Association) to express concerns with the legislation and urge senators to vote no on the bill. Yesterday, Immediate Past APA President Maria A. Oquendo, M.D., Ph.D., joined leaders of these organizations on Capitol Hill to visit key Senate offices.

APA members are urged to contact their senators through a special portal on the APA website.

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Thursday, July 13, 2017

Antidepressant Use in Pregnancy and Intellectual Disability in Offspring Not Associated, Concludes Study


An international team of researchers analyzing data from a large Swedish national registry concluded there is no association between antidepressant use during pregnancy and intellectual disability in offspring. The report was published yesterday in JAMA Psychiatry.

Researchers led by Alexander Viktorin, Ph.D., of the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai, analyzed data from the Swedish Prescribed Drug Register and the Swedish National Patient Registry to estimate relative risks (RRs) for intellectual disability in children exposed during pregnancy to antidepressant medication. They also analyzed the risk associated specifically with selective serotonin reuptake inhibitor (SSRI) antidepressants, all other non-SSRI antidepressants, and other nonantidepressant psychotropic medications.

Intellectual disability was defined as having at least one inpatient or outpatient specialist care admission between birth and the end of follow-up at December 31, 2014, with an ICD-10 code of F70 to F79.

Of the 179,007 children in the study, an intellectual disability was diagnosed in 0.9% of those exposed to antidepressants and in 0.5% of those not exposed. The unadjusted RR of intellectual disability in the children exposed to maternal antidepressant medication use during pregnancy was estimated at 1.97. However, when the data were adjusted for parental age, the psychiatric illness for which the mother was treated, and other variables unrelated to the medication, the increased risk disappeared and the relative risk was statistically nonsignificant.

Moreover, the analyses of risks for children born to mothers treated during pregnancy specifically with SSRI antidepressants, non-SSRI antidepressants, or nonantidepressant psychotropic medications were comparable to the analyses of children exposed to any antidepressant during pregnancy.

For related information see the Psychiatric News article “SSRI Use During Pregnancy May Increase Risk of Language Delays in Offspring.”

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Wednesday, July 12, 2017

Binge Eating Medication Found Effective as Maintenance Therapy


A multinational clinical study involving more than 400 participants with binge eating disorder (BED) has found that lisdexamfetamine is significantly more effective than placebo at preventing relapse of binge eating symptoms. At the end of the six-month study, only 3.7% of patients taking lisdexamfetamine experienced a relapse compared with 32.1% of patients taking placebo.

These findings, published today in JAMA Psychiatry, provide the first evidence of lisdexamfetamine’s effectiveness as a maintenance therapy for BED.

The safety and tolerability profiles of lisdexamfetamine were favorable as well, noted lead author James Hudson, M.D., Sc.D., of Harvard Medical School and colleagues. “Overall, there was no evidence of new trends in the safety profile of lisdexamfetamine following long-term treatment or abrupt discontinuation,” they wrote.

For this study, 418 adults with moderate to severe BED (defined as at least three binge eating days per week and Clinical Global Impression-Severity [CGI-S] scores of 4 or higher) were recruited at 49 sites across the globe. All the participants initially received 12 weeks of lisdexamfetamine therapy (50 mg or 70 mg once daily); the 275 responders were then randomized to continue lisdexamfetamine therapy or placebo for 26 weeks.

Lisdexamfetamine also outperformed placebo on secondary measures, including total binge eating days per week, CGI-S scores, and obsessive-compulsive symptom scores.

“Although the clinical significance of the findings is unclear, a large proportion of participants in the placebo group failed to relapse,” the authors wrote. “This is an important issue because it could have implications for how recommendations about the need for long-term lisdexamfetamine use in individuals with BED who respond to lisdexamfetamine acutely are made.”

This study was supported by Shire Development LLC, manufacturer of lisdexamfetamine (Vyvanase).

To read more about this topic, see the Psychiatric News articles “FDA Approves First Drug for Binge-Eating Disorder” and “New DSM Guide Describes Changes to Eating, Elimination, Sleep Disorders Criteria.”
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Want to Learn About Reimbursement for Psychiatric Collaborative Care Services?

APA is presenting a free webinar on Thursday, July 13, from noon to 1 p.m. that explains how to get paid for collaborative care services. This past January, the Centers for Medicare and Medicaid Services authorized payment for these services using HCPCS codes that describe the work of this model of care. Join the webinar and learn more about the billing and documentation requirements associated with the new codes. Register now!

APA is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. APA designates this live activity for a maximum of 1 AMA PRA Category 1 Credit.

Tuesday, July 11, 2017

Augmentation With Aripiprazole Found Superior When MDD Patients Don't Respond


Augmentation of antidepressant treatment with aripiprazole showed a modest but statistically significant advantage in terms of both remission and response over switching to bupropion in a population of predominantly male veterans with treatment-resistant depression.

That’s the finding from the VA Augmentation and Switching to Improve Depression (VAST-D) Study reported today in JAMA. Lead author Somaia Mohamed, M.D., Ph.D. (pictured left), of the VA Connecticut Healthcare System and colleagues cautioned that further cost-effectiveness analysis is needed given the small effect size and adverse effects associated with aripiprazole.

In comments to Psychiatric News, Mohamed said that since only a third of patients benefit from their first antidepressant treatment, clinicians typically have to choose a new medication on the basis of trial and error. “This study presents the first data indicating that adding an antipsychotic may be more effective than switching to a new antidepressant,” she said. “This study may encourage clinicians to try antipsychotics earlier than they might have otherwise.”

The study was a a multisite randomized trial with Veterans Health Administration (VHA) patients whose condition was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dose and duration. Patients at 35 VA medical centers were randomized to one of three treatments: switch to another antidepressant, bupropion sustained release (switch group); augment current treatment with bupropion sustained release (augment-bupropion group); or augment current treatment with an antipsychotic, aripiprazole (augment-aripiprazole group).

Rates of remission (defined as absence of symptoms) at 12 weeks were 22.3% for the switch group, 26.9% for the augment-bupropion group, and 28.9% for the augment-aripiprazole group. Response (defined as 50 percent reduction in symptoms) was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%) or the augment-bupropion group (65.6%).

In an accompanying editorial, Maurizio Fava, M.D., said the VAST-D study extends findings of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. “Because the VAST-D study was implemented solely in VA sites, the population studied was predominantly male (85%), a significant difference from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D,” he wrote.

Accordingly, the study cannot determine whether the results would have been different in a predominantly female population of patients with MDD. However, a pooled analysis of two trials comparing aripiprazole augmentation with placebo augmentation among patients with MDD and inadequate response to antidepressant therapy found that aripiprazole augmentation was actually more effective for women than men. This argues that the VAST-D study may have underestimated the relative benefit of aripiprazole augmentation.”

For information about VAST-D, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don't Respond.”

Monday, July 10, 2017

Bipolar Risk Calculator Developed for At-Risk Youth


In a study published last week in JAMA Psychiatry, researchers reported the development of a calculator to predict the onset of a bipolar spectrum disorder (BPSD) in at-risk youth.

BPSD was defined under DSM-IV criteria as bipolar I, bipolar II, cyclothymic disorder, or bipolar not otherwise specified.

The BPSD risk calculator was found to be approximately 76% accurate, which is on par with a recently developed risk calculator for new-onset psychosis as well as risk calculators used in other areas of medicine.

“We recognize that replication of these findings is warranted before the risk calculator can be confidently used for clinical decision making,” wrote lead author Danella Hafeman, M.D., Ph.D., of the University of Pittsburgh and colleagues. “In the interim, this risk calculator provides a practical tool for assessing the prognosis [of] and guiding monitoring and early intervention for offspring of parents with BD.”

Hafeman and colleagues built their calculator by incorporating seven commonly occurring risk factors for BPSD that included measures of mood and anxiety, measures of general psychosocial functioning, and age at mood-disorder onset in the parent with bipolar disorder. They then tested their model on youth enrolled in the Pittsburgh Bipolar Offspring Study, a community-based, longitudinal investigation that monitors children of parents with bipolar I or II disorder.

The study encompassed 412 at-risk offspring who had not yet experienced a manic, hypomanic, or mixed episode and included 1,058 clinician visits by these offspring where risk scores were calculated. The researchers found that the risk calculator could discriminate between a converting visit—defined as the patient being diagnosed with a BPSD within five years of the visit—versus a nonconverting visit 76% of the time.

Consistent with existing research, the parental age at mood disorder onset proved to be the most important single predictor of risk among the seven criteria included in the calculator.

“To date, research in youth at familial risk for BD has mainly focused on psychopathology, description of clinical characteristics, and potential risk factors,” wrote Esther Mesman, Ph.D., and Manon Hillegers, M.D., Ph.D., of the University of Utrecht in the Netherlands in an accompanying editorial. “Hafeman and colleagues propose an individual risk calculator for youth at familial risk for BD, an important consideration for the field of BD. Nonetheless, risk assessment is only valuable if early intervention methods and treatments are available, which should be investigated in parallel.”

To read more about this topic, see the Psychiatric News article "Experts Make Case for Lithium in Youth With Bipolar Disorder."

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Want to Learn About Reimbursement for Psychiatric Collaborative Care Services?

APA is presenting a free webinar on Thursday, July 13, from noon to 1 p.m. that explains how to get paid for collaborative care services. This past January, the Centers for Medicare and Medicaid Services authorized payment for these services using HCPCS codes that describe the work of this model of care. Join the webinar and learn more about the billing and documentation requirements associated with the new codes. Register now!

APA is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. APA designates this live activity for a maximum of 1 AMA PRA Category 1 Credit.

Friday, July 7, 2017

Alzheimer’s Disease May Be More Likely to Be Missed in Patients With Psychosis


About one in four cases of Alzheimer’s disease (AD) is misdiagnosed, according to a study published online in Alzheimer's & Dementia: Translational Research & Clinical Interventions. In particular, patients with a history of psychosis were found to be more likely to be clinically misdiagnosed with other forms of dementia.

“Psychosis can be a symptom of Alzheimer’s disease, but it is a defining clinical feature in other types of dementia, including Parkinson’s disease dementia and dementia with Lewy bodies,” Corinne Fischer, M.D., director of the Memory Disorders Clinic at St. Michael’s Hospital in Toronto and lead author of the study, said in a press release. “Consequently, clinicians are more reluctant to diagnose a patient with Alzheimer’s disease when they present with delusions or hallucinations.”

Misdiagnosis of AD has significant implications for clinical care because patients may not receive appropriate treatment, which can impact clinical outcomes. For example, treatment with existing cholinesterase inhibitors has shown some effectiveness in AD, but limited effectiveness in other forms of dementia, such as vascular dementia and frontotemporal dementia.

Fischer and colleagues examined 961 people using data from the National Alzheimer’s Coordinating Center (NACC) database, collected from 29 Alzheimer’s disease centers in the United States between 2005 and 2012. They included participants who had been clinically diagnosed with AD while they were alive, and those whose autopsies showed the signature physical signs of AD in their brains.

A total of 76% of the patients received a correct AD diagnosis, 11.9% had a false-negative diagnosis, and 12.1% had a false-positive diagnosis of AD, the authors reported. Patients with psychosis had a higher rate of false-negative diagnosis and a lower rate of false-positive diagnosis of AD compared with nonpsychotic patients.

The researchers noted that most patients in the NACC database have been examined by clinicians with particular expertise in dementia, and the diagnosis given was the last one before death. Thus, the rates of misdiagnosis in this study should be considered to represent the minimum, reached under very favorable conditions. “If you extrapolate that and apply it to the general population, the magnitude of the problem could be much greater,” they wrote.

For related information, see the Psychiatric News article “New Dementia Measures Address Disclosure of Diagnosis to Patients.”

(Image: iStock/fzant)

Thursday, July 6, 2017

ADHD Medications Do Not Increase Substance-Related Problems, Study Suggests


Use of medication for attention-deficit/hyperactivity disorder (ADHD) does not appear to increase the risk of substance-related problems in adolescent and adult patients with ADHD, and among males it may even be protective against later substance-related problems, according to a report in AJP in Advance

“Our results cannot speak to the possibility of diversion or misuse of stimulants outside of treatment,” Patrick D. Quinn, Ph.D., of Indiana University and colleagues wrote. “However, they do join a growing evidence base of protective associations for patients receiving medication therapy. It may be useful to consider these associations in conjunction with other potential benefits and harms (such as growth delay) when making treatment decisions.”

Quinn, together with colleagues from American and Swedish institutions, used data from the Truven Health MarketScan Commercial Claims and Encounters (MarketScan) databases of de-identified inpatient, outpatient, and prescribed drug claims for commercially insured individuals. They identified 2,993,887 ADHD patients who received either an ADHD diagnosis or stimulant or atomoxetine ADHD medication treatment. Patients were followed from first inpatient or outpatient diagnosis or filled prescription until December 2014 (or the last month of enrollment in their health plan). A “substance-related event” was defined as at least one emergency department claim with “any non-tobacco-related substance use disorder diagnosis” during a month in which the individual was medicated for ADHD.

Relative to periods in which patients did not receive ADHD medication, male patients had 35% lower odds of concurrent substance-related events when receiving medication, and female patients, 31% lower odds. Moreover, ADHD medication predicted a 19% reduction in the odds of substance-related events two years later among male patients and a 14% reduction among female patients.

In comments to Psychiatric News, child psychiatrist and past APA Trustee David Fassler, M.D., a clinical professor of psychiatry at the University of Vermont, noted that the authors appropriately considered and discussed alternative explanations for their findings, which cannot be definitively excluded due to the observational nature of the study. “However, I agree with their conclusion that the current results join a growing body of evidence supporting the protective factors associated with timely and appropriate treatment for ADHD in both adolescents and adults,” he said. 

For related information, see the Psychiatric News article “Medicated ADHD Patients Have Reduced Risk of Motor Vehicle Crashes.” 

(Image: KatarzynaBialasiewicz/istock.com)

Wednesday, July 5, 2017

Fluoxetine Found to Reduce Symptoms of Hypochondria


Patients experiencing symptoms of hypochondriasis may benefit from taking fluoxetine, according to a study in AJP in Advance.

“Although hypochondriasis was not retained as a diagnosis in DSM-5, the new diagnoses of illness anxiety disorder and somatic symptom disorder both retain health/illness anxiety as a prominent feature; therefore, we anticipate that the results from this trial will be generalizable to many individuals with these DSM-5 diagnoses,” Brian A. Fallon, M.D., director of the Center for Neuroinflammatory Disorders and Biobehavioral Medicine at Columbia University, and colleagues wrote.

Fallon and colleagues randomly assigned 195 adults with DSM-IV hypochondriasis to one of four treatment conditions: placebo, cognitive-behavioral therapy (CBT), fluoxetine, or joint treatment with both fluoxetine and CBT for 24 weeks. At the start of the trial and again at 6, 12, and 24 weeks later, the patients underwent a battery of tests, which assessed hypochondriacal symptoms, other psychopathology, adverse events, functional status, and quality of life.

Patients assigned to CBT received six in-person, 60-minute weekly sessions with a therapist, followed by two biweekly and three monthly booster sessions. Patients assigned to fluoxetine received the medication on a fixed-flexible dosing regimen, beginning at 10 mg daily and increasing as tolerated and needed to 80 mg/day. 

The researchers compared the proportion of responders in each treatment group. Response was defined as improvement of at least 25% over baseline scores on both the Whiteley Index and the Yale-Brown Obsessive Compulsive Scale for hypochondriasis (H-YBOCS-M). 

The researchers found that patients who received either fluoxetine, CBT, or a combination of the two had better response rates than those who received placebo (41.84% in the individual active treatment group and 47.17% in the joint treatment group compared with 29.55% in the placebo group). Secondary analyses of the Whiteley Index score revealed that fluoxetine was significantly more effective than placebo and was associated with a significantly faster rate of improvement over 24 weeks. Compared with placebo, patients receiving fluoxetine also had significantly lower anxiety scores and higher quality of life scores. There were no significant differences between treatment-emergent adverse events or dropout rates across the groups. 

“The improvement with fluoxetine could not be accounted for by improvement in depression alone, as the difference in depression scores over time was not significant. This suggests that pharmacotherapy had a relatively specific effect on hypochondriacal symptoms,” Fallon and colleagues wrote. “In contrast to hypochondriasis, somatization did not improve in any of the treatment arms.”

(Image: Pressmaster/Shutterstock)

Monday, July 3, 2017

Long-Acting Buprenorphine Formulation May Reduce Cravings While Lowering Misuse Risks


Buprenorphine is a widely used therapy for opioid use disorder (OUD), but the daily sublingual formulations currently available do have their own issues. These include adherence difficulties as well as the risk of misuse or diversion.

A clinical study published in JAMA Psychiatry has now tested a new, weekly injectable form of buprenorphine called CAM2308. “CAM2038 produced clinically relevant buprenorphine plasma levels, translating into rapid and sustained opioid blockade and withdrawal suppression, and was well-tolerated both systemically and locally. Findings suggest that CAM2038 formulations will be effective in reducing illicit opioid use and relapse, while eliminating the risk for misuse and diversion,” wrote Sharon Walsh, Ph.D., of the Center on Drug and Alcohol Research at the University of Kentucky and colleagues.

For this study, supported in part by CAM2038 manufacturer Braeburn Pharmaceuticals, 47 adults with moderate-to-severe OUD were randomized to received two doses of either 24 mg or 32 mg of CAM2038 one week apart. Immediately prior to and four times during the two-week trial, the participants were also randomized to receive a placebo or 6 mg or 18 mg of the opioid hydromorphone for three consecutive days in order to illicit “drug liking” responses and evaluate CAM2038 response.

Walsh and colleagues observed that both weekly CAM2038 doses produced rapid and sustained inhibition of hydromorphone’s euphoria-inducing effects, even at the 18-mg hydromorphone dose. CAM2038 was also able to effectively suppress opiate withdrawal symptoms throughout the two-week study period.

Adverse events due to CAM2038 were reported by a little more than half of the participants and mostly rated as mild. Constipation, injection-site pain, and headache were the most common effects reported.

This study was also supported by the National Institute on Drug Abuse National Center for Research Resources and the National Center for Advancing of Translational Sciences.

To read more about this topic, see the Psychiatric News article “Tackling Opioid Overdose Epidemic Demands Multiple Approaches.”

(Image: iStock/Ca-ssis)

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