APA President Calls For Enhanced Efforts to Alleviate Mental Health Crisis in U.S. Jails

“The criminalization of mental illness is a national tragedy,” APA President Renée Binder, M.D., told an audience gathered yesterday for a congressional briefing on Capitol Hill.

The event, which was sponsored by APA, aimed to promote awareness of the numerous challenges people who are living with mental illness in U.S. jails and prisons face and highlight possible policy solutions to help meet the needs of this population.

People with mental illness in U.S. jails and prisons often spend more time behind bars than those without such disorders, said Binder, a forensic psychiatrist. They also tend to incur more infractions and are more vulnerable to victimization by other inmates—all in a setting not designed or equipped to provide them with treatment.

Binder, together with other leading experts in psychiatry, mental health, and law enforcement who spoke at the meeting, called for enhanced efforts to change the way that people living with mental illness who have been incarcerated are treated.

“Local and state leaders must join with criminal justice, mental health, and substance use professionals to steer and support long-term efforts to move mental health care from our jails to the community,” said Mary Ann Borgeson, who has served as county commissioner in Douglas County, Neb., for 21 years. “But we can’t do it alone. We need federal leadership and we ask Congress to make the efforts needed to reduce the criminalization of people with mental illness.”

According to the speakers, some of the nation’s 3,069 counties have already started to change the way they treat people with mental illness who intersect with the criminal justice system, including modifications in arrest policies and law enforcement training, the establishment of mental health courts, and the development of re-entry supported housing programs.

“However, we need to give local jurisdictions help to decrease the number of people with mental illness behind bars,” Binder said, noting the array of bills targeting mental health reform already proposed in both the House and Senate.

“Numerous provisions in these bills would give local jurisdictions the support they need to reduce the number of persons with serious mental illnesses who are jailed each year,” Binder wrote today in a blog post. “The APA has taken the lead in collaborating with leaders in Congress toward the furtherance of these goals, but we can’t do it alone. I urge you to get involved with your state and local legislature and communicate to them the unique issues that your community faces in regards to the criminalization of people with mental illness.”

For more about people with mental illness in U.S. jails, see the Psychiatric News article, “Counties Seek Help to Reduce Numbers of Mentally Ill Inmates.”

(Image: David Hathcox)

Expert Makes Case to Use Lithium for Youth With Bipolar Disorder

Treating young patients with bipolar disorder can be challenging, but a growing body of evidence suggests lithium may be a good place to start, Vivian Kafentaris, M.D. (pictured left), said Tuesday at the annual meeting of the American Academy of Child and Adolescent Psychiatry in San Antonio.

“It is important that we recognize bipolar disorder early in youth and treat the disorder as early as possible,” said Kafentaris, the director of research in the Division of Child and Adolescent Psychiatry at Hofstra North Shore-LIJ School of Medicine. “A lot of people—both children and adults [with bipolar disorder]—have been on a multitude of medications but never on lithium.”

During her presentation, Kafentaris offered an overview of evidence-based strategies of off-label drugs for treating children and adolescents with bipolar disorder. In particular, she highlighted some data from the Collaborative Lithium Trials, which compared patients (aged 7 to 17 years) with bipolar I/manic or mixed episodes who were treated with lithium for up to 8 weeks with those treated with placebo.

The study, which was published this month in Pediatrics, found that those in the lithium group experienced a greater reduction in manic symptoms (as measured by changes in the Young Mania Rating Scale and Clinical Global Impression–Improvement scores) than those taking placebo. Additionally, the medication was generally well tolerated and was not associated with weight gain.

“The earlier lithium is instituted, the more likely it is to be effective,” Kafentaris told Psychiatric News. “If we wait and the severity of the illness progresses, then we run the risk of having to use multiple therapies to achieve mood stabilization.”

Although Kafentaris expressed optimism over the positive results of lithium treatment in children and adolescents with bipolar I disorder, she emphasized that more research is needed to determine the long-term effects of medication in youth.

For related information, see the Psychiatric News article “Lithium Is Regaining Favor Over Anticonvulsants.”

(Image: Vabren Watts/Psychiatric News)

APA Announces Candidates for 2016 Election

The APA Nominating Committee, chaired by APA Immediate Past President Paul Summergrad, M.D., today announced the candidates for the Association's 2016 election.

PRESIDENT-ELECT
Frank W. Brown, M.D.
Anita S. Everett, M.D.

TREASURER
Bruce J. Schwartz, M.D.
Linda L.M. Worley, M.D.

TRUSTEE-AT-LARGE
Rebecca W. Brendel, M.D., J.D.
Geetha Jayaram, M.D.
Richard F. Summers, M.D.

AREA 3 TRUSTEE
Steven R. Daviss, M.D.
Roger Peele, M.D.

AREA 6 TRUSTEE
Robert P. Cabaj, M.D.
Melinda L. Young, M.D.

RESIDENT-FELLOW MEMBER TRUSTEE-ELECT
Adrian Jacques H. Ambrose, M.D.
Uchenna B. Okoye, M.D., M.P.H.
Matt Salmon, D.O.

The deadline for candidates who wish to run by petition is November 15. All candidates and their supporters are encouraged to review APA's Election Guidelines. For more election information, please visit the Election section under the "Board of Trustees" on the APA website or email election@psych.org.

The slate of candidates who have been nominated is public but not official until approved by the APA Board of Trustees at its December meeting. Voting for the 2016 election will be open from January 4 to February 1, 2016.

Genotyping, Drug Metabolism Status May Predict Clinical Response to Risperidone

The presence of a genetic polymorphism and the speed with which a patient metabolizes risperidone may help to predict those with schizophrenia who are the most likely to respond to the medication, according to a report in AJP in Advance. The findings highlight the potential for genotype-guided pharmacotherapy in the management of schizophrenia patients, the authors wrote.

Researchers from Australia, the United States, and Wales analyzed the effects of drug metabolism and variants of the potassium channel gene KCNH2 on clinical responses to antipsychotic medications among patients enrolled in the multicenter Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Previous studies have found that patients who have KCNH2 genotypes associated with increased expression of the potassium channel known as Kv11.1-3.1 tend to have a better response to antipsychotic medications in general.

The researchers found that in the CATIE study (N=362), patients with genotypes associated with increased Kv11.1-3.1 expression showed a better treatment response to risperidone compared with other drugs, but this association was dependent on metabolism status. That is, patients with KCNH2 risk genotypes and slow metabolizer status (approximately 7% of patients) showed marked improvement in symptoms when treated with risperidone compared with patients with fast metabolizer status or without the KCNH2 risk genotypes.

While the authors noted that more research is needed to inform clinical decision making, they concluded, “The data in this study strongly suggest that schizophrenia patients who are slow metabolizers and have KCNH2 risk-associated genotypes do better when treated with risperidone than with other antipsychotics, and they have by far the best response of anyone in the CATIE trial.”

For related information, see the Psychiatric News article “Blood Test May Predict Patients Likely to Develop Schizophrenia.”

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APA Takes Action on Problems with Clozapine REMS

Last month, the FDA announced that beginning on October 12, all prescribers of clozapine—a medication used for the treatment of schizophrenia—are required to be certified in a Clozapine REMS (Risk Evaluation and Mitigation Strategy) Program. This change was part of an effort to improve the monitoring and management of patients taking the medication. Since the program’s launch, however, APA members have reported numerous technical, personnel, and process problems that they say could affect the appropriate prescribing and dispensing of clozapine.

Several challenges with the FDA’s Clozapine REMS rollout have been reported, including the following:

* Technical issues related to website operation and certification.
* Intermittent or nonexistent access to customer service representatives.
* Issues related to a certified prescriber’s ability to cover for or designate others to prescribe clozapine such as psychiatric residents.
* Unnecessary registration burdens that could create potentially harmful delays in the initiation or discontinuation of clozapine treatment.

In response, the FDA recently released an alert stating that prescribers and pharmacists should continue clozapine prescribing and dispensing, using their clinical judgment to consider the best interests of the patient even if they encounter problems with the Clozapine REMS certification program.

APA has been in contact with the FDA to share its clinical concerns and has agreed to collaborate to effect an appropriate implementation of the clozapine REMS. APA will also continue to gather information from its district branch and state association executives as well as the APA councils on Research and Quality Care.

To read more about the issues around clozapine, see the Psychiatric News article “Why Won't Clinicians Use Clozapine Despite Proven Superiority?”

Safest Course to Prevent Fetal Alcohol Syndrome: No Drinking in Pregnancy

Prenatal exposure to alcohol is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities, according to a report from the American Academy of Pediatrics. The article, which appeared online this week in the journal Pediatrics, notes that no amount of alcohol should be considered safe and that there is no safe trimester in which to drink.

Children born with fetal alcohol spectrum disorder (FASD) or its variants are more likely than the general population to develop concurrent psychiatric, emotional, and behavioral problems, according to the lead authors Janet Williams, M.D., of the University of Texas Health Science Center in San Antonio and Vincent Smith, M.D., M.P.H., of Boston Children’s Hospital.

“Children and adolescents with FASD have a 95% lifetime likelihood to experience mental health issues, and among the most prevalent are anxiety and mood disorders, particularly depression, as well as ADHD, substance use, addiction, and suicide,” they wrote.

The structural and functional effects of prenatal exposure to alcohol on the brain may also be accompanied by problems in other organ systems, including the heart, kidneys, eyes, ears, and musculoskeletal system.

“Multimodal symptom treatments that improve long-term outcomes [for FASD] include optimizing environmental modifications, parenting strategies, social support, and developmental and educational interventions that address the neurologically based problems related to FASDs,” wrote the authors. Far better than treatment, the experts note, is prevention, however.

“The research suggests that the smartest choice for women who are pregnant is to just abstain from alcohol completely,” Williams said in a press release.

For more information about fetal alcohol syndrome, see the Psychiatric News article “Growing Recognition of Prevalence of Disorders Brought on by Prenatal Alcohol Exposure.”

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Linguistic Analysis of Clinicians’ Notes May Identify Patients at Greatest Risk of Suicide

An analysis of the language that clinicians use in notes to describe encounters with their patients may offer clues about those most likely to die from suicide, according to a study appearing in the October issue of Psychiatric Services.

Recent use of the health care system by those who die from suicide has long been recognized as an opportunity for intervention. However, in the context of clinical care, suicide can be difficult both to predict and prevent. While linguistic analysis has revealed unique language patterns in the notes of individuals who later died by suicide, less is known of whether the notes written by the clinicians for such patients differ from the notes for those who do not die from suicide.

Researchers from the White River Junction Veterans Affairs (VA) Medical Center in Vermont analyzed the notes taken by the clinicians of 63 U.S. military veterans who died from suicide during 2009—approximately half of whom had received mental health services in the year prior to their death. The researchers then compared these clinical notes with those for 63 VA outpatients who were living in 2009 chosen on the basis of age, gender, VA priority group, and whether they received mental health services within the prior year.

The authors found that the clinical notes for patients who obtained mental health services and later died from suicide contained more “distancing language,” such as greater use of third-person pronouns, than the notes describing the other mental health service users. The analysis also revealed the more frequent use of such language as the time of suicide approached.

“These findings suggest that more frequent use of distancing language by clinicians is a predictor of suicide among mental health service users. If replicated in additional studies, this finding could have important implications in the identification of suicide risk,” the study authors wrote. While the researchers acknowledged that “linguistic trends are likely invisible to a practicing clinician … routine linguistic analysis of clinical notes could be shown to clinicians … to help guide psychotherapy practice.”

The authors also suggested that this information could be combined with other demographic and risk factor information to help create a “more comprehensive risk profile to guide clinical decision making and to help individual clinicians tailor their interpersonal style to their patients’ needs.”

For related information, see the Psychiatric News article “Two-Part Assessment May Help Predict Suicidal Behavior, Study Finds.”

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CBT May Help Reduce Relapse in MDD Patients Who Are Tapering, Discontinuing Antidepressants

Patients with major depressive disorder (MDD) who participate in psychotherapy after responding to acute-phase pharmacotherapy may have a lower risk of relapse and recurrence when tapering antidepressants, according to a meta-analysis published Tuesday in AJP in Advance.

Researchers from the University of Bologna in Italy and University of New York at Buffalo performed a systematic review of randomized, controlled trials that examined the effectiveness of the administration of psychotherapy after successful response to acute-phase pharmacotherapy in the treatment of adults with MDD.

The researchers included 13 trials (including 1,410 participants aged 18 and older)—all of which involved cognitive-behavioral therapy (CBT)—in their analysis. They found that patients who were randomly assigned to receive CBT while antidepressants were discontinued were significantly less likely to experience relapse/recurrence compared with those assigned to either clinical management during tapering of antidepressants or continuation of antidepressant medication.

“The average depressed patient appears to express stronger preferences for psychotherapy than for antidepressant medications, a finding that is of considerable clinical importance given that treatment preference is a potent moderator of response to therapy,” the study authors wrote. “The sequential modality of integration of pharmacotherapy and psychotherapy appears to be a valuable therapeutic strategy for preventing relapse.”

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

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RAISE Study Shows Benefit of Comprehensive Psychosocial Treatment of First-Episode Psychosis

First-episode psychosis patients who participated in a comprehensive, team-based treatment program at community-based clinics that included a combination of medication and psychosocial support experienced significant improvements in symptoms and quality of life compared with those receiving usual care.

That’s the finding from a landmark study appearing today in AJP in Advance of the NIMH-funded Recovery After an Initial Schizophrenia Episode (RAISE) initiative. Importantly, the study also found that the best results were for patients who had shorter durations of psychosis, underscoring the importance of early intervention.

The study received widespread coverage including a report in the New York Times that cited experts who said the study could help to dramatically change the way first-episode patients are treated. 

Lead study author John Kane, M.D., chair of the psychiatry department at Hofstra North Shore-LIJ School of Medicine, and colleagues at multiple institutions used a model called NAVIGATE that includes four core interventions: personalized medication management, family psychoeducation, resilience-focused individual therapy, and supported employment and education. The model was delivered at community-based clinics to mirror real-world settings.

Thirty-four community mental health treatment centers in 21 states were randomly assigned to the experimental intervention (n=17) or to standard care (n=17). A total of 223 patients received the experimental NAVIGATE intervention, and 181 participants received usual care.

The study found that NAVIGATE patients remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with patients in community care. NAVIGATE participants with duration of untreated psychosis of less than 74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care.

Kane and colleagues wrote, “RAISE-ETP is the first multisite, randomized, controlled trial of coordinated specialty care conducted in the United States, and the first anywhere to simultaneously include all of the following elements: randomized concurrent controls; masked assessment of primary and secondary outcomes; and manual-driven intervention with ongoing training and fidelity metrics. Most importantly, NAVIGATE improved outcomes for patients over 24 months.”

In an accompanying editorial, NIMH Director Thomas Insel, M.D., noted that “one of the most remarkable aspects of this study was the substantial moderation of the treatment effect by the duration of untreated psychosis. … These results demonstrate the importance of early detection, early engagement, and integrated care following the onset of psychosis.”

The National Alliance on Mental Illness (NAMI) plans to use this program and study findings in support of a major campaign to promote broader adoption of coordinated specialty care services throughout the states for people experiencing first-episode psychosis. As part of this effort, NAMI has arranged a Congressional briefing that is taking place this afternoon in which Kane, and Lisa Dixon, M.D., will present the RAISE comparative effectiveness and implementation results. Coverage of the briefing will appear in a future issue of Psychiatric News.

For related information, see the Psychiatric Services article “Implementing Coordinated Specialty Care for Early Psychosis: The RAISE Connection Program.”

Study Finds People Who Will Develop HD Show Signs of Early Psychiatric Symptoms

Psychiatric symptoms are a significant component of Huntington’s disease (HD), but the manifestation and progression of these symptoms are highly variable. Some studies have even suggested that the severity of psychiatric symptoms is not associated with the progression of the disease.

A large longitudinal study that tracked patients with prodromal Huntington’s disease now suggests that people who go on to develop Huntington’s disease show signs of psychiatric symptoms prior to the onset of motor symptoms that continue to worsen as the disease progresses. The study, which included 1,007 people carrying the Huntington’s disease mutation, 298 controls with no mutation, and 1,235 companions, identified 19 psychiatric measures (out of 24 assessed) that were significantly higher at baseline and increased over time in the individuals with the disease mutation compared with controls. The findings were published on Friday in AJP in Advance.

The differences in the psychiatric measures between patients and controls were greatest when they were rated by companions rather than the participants with the Huntington’s disease mutation—findings consistent with observations that individuals with Huntington’s disease have a decreased awareness of their symptoms as the disease progresses.

“The results reported here provide initial information regarding psychiatric symptoms that occur in individuals who will develop Huntington’s disease and the importance of obtaining assessments from companions,” the study authors wrote. “This is critical to consider in future studies that assess behavioral manifestations and psychiatric symptoms, including those that investigate their underlying pathophysiology in Huntington’s disease and in therapeutic trials, as well as clinical assessment and management of persons who will develop Huntington’s disease.”

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PET Reveals Inflammatory Response in Schizophrenia, High-Risk Patients

Microglial activity—indicative of an immune response to neuroinflammation—appears to be elevated in the brains of people with schizophrenia and those at high risk of developing schizophrenia, according to a study published today in AJP in Advance. Moreover, the elevated microglial activity appears to be related to symptom severity.

Researchers at the Medical Research Council’s Clinical Sciences Centre, based at Imperial College London, in collaboration with colleagues at King’s College London used positron emission tomography (PET) to measure in vivo microglial activity in patients with schizophrenia, high-risk individuals with pre-clinical symptoms, and healthy controls. (Microglial cells are the immune cells of the brain and are similar to immune-responsive macrophages in the blood; their presence in large numbers indicates inflammation.) The PET method employed a radioactive tracer specific for a protein (known as 18kD translocator-protein, or TSPO) that is indicative of microglial activity.

A total of 56 participants completed the study, including 14 people who met ultra-high risk criteria, as assessed on the comprehensive assessment of the at-risk mental state (CAARMS) and 14 age-matched controls; an additional 14 people with schizophrenia and 14 age-matched healthy controls also participated in the trial.

The authors found that the protein-binding ratio in gray matter was elevated in ultra-high risk subjects compared with matched controls and was positively correlated with symptom severity. Patients with schizophrenia also demonstrated elevated microglial activity with respect to matched controls. Importantly, the researchers found no relationship between depressive symptom severity and the protein binding ratio in gray matter in patients with schizophrenia or ultra-high-risk participants, suggesting the elevated microglial activity is specific to the development of psychotic-like symptoms, rather than psychiatric symptoms in general.

“This is a promising study, as it suggests that inflammation may lead to schizophrenia and other psychotic disorders,” study author Oliver Howes, M.D., Ph.D., said in a press release. “We now aim to test whether anti-inflammatory treatments can target these. This could lead to new treatments or even prevention of the disorders altogether.”

AJP Editor Robert Freedman, M.D. (pictured above), told Psychiatric News that both the findings from the study and the application of the PET method to image pathophysiological processes in the brain may prove transformative. “The PET method now gives clinical researchers an invaluable tool, not before available, to monitor this transition and to search for what might be causing the inflammation,” he continued. “If anti-inflammatory interventions are attempted, then this method can assess whether the intervention has its intended effect.”

For related information, see the Psychiatric News article “Blood Test May Predict Patients Likely to Develop Schizophrenia.”

AJP Commentary Explores Challenges Associated With Domestic Violence

Mental illness can both arise from and increase a person’s risk of becoming a victim of domestic violence, but psychiatry and clinical psychology “are largely absent from domestic violence research and intervention,” wrote Anna Chapman, M.D., a clinical instructor in psychiatry at Weill Cornell Medical College, and Catherine Monk, Ph.D., an associate professor of psychiatry, behavioral medicine, and developmental neuroscience at Columbia University Medical Center in an article in the current issue of the American Journal of Psychiatry.

In the commentary, which was released to coincide with Domestic Violence Awareness Month in October, Chapman and Monk noted that “[d]espite its prevalence in the general population, domestic violence is underrepresented in our consulting rooms in part because victims, and especially perpetrators, rarely voluntarily self-identify or seek treatment.”

The authors go on to describe the challenges associated with treating individuals in domestic violence relationships—including safety planning and patients’ minimization of abuse—and several targeted treatment programs for domestic violence intervention, though they noted “few psychologists and psychiatrists are trained in them.”

“Evoking deep, psychological concerns, we retreat from domestic violence, drawing a line in the sand between ‘our’ behaviors and ‘theirs,’” concluded Chapman and Cook. “We tend to pity and disdain the victim, and vilify the abuser, abdicating our roles as clinicians and researchers. It is the mandate of the criminal justice system to punish people for violent actions and of social services to support victims. As the leading fields in mind, brain, and behavior, it is our mandate to understand and rehabilitate all human behavior, without prejudice.”

For more in Psychiatric News about domestic violence, see “Domestic Violence Awareness Month: Clinicians May Be First Responders.”

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How to Avoid Having Your 1500 Forms Returned

APA learned today that Medicare providers who file 1500 Health Insurance Claim Forms are having a large number of their claims returned due to a change in the reporting requirements that went into effect on October 1, 2015.

Medicare contractors are returning claims for correction or resubmission to mental health professionals who fail to indicate in line item 21 of the 1500 claim form whether ICD-9 or ICD-10 codes are used.

For services that were provided prior to October 1, 2015, ICD-9 codes should be used even if the claim is filed after that date; for services on or after October 1, 2015, ICD-10 codes should be used. ICD-9 codes are indicated by using a 9 in item #21; ICD-10 codes are noted with a 0.

DSM-5 lists both the ICD-9 and the ICD-10 codes for each diagnosis. The ICD-9 codes are in black ink and the ICD-10 codes are to the right of them in gray ink.

For information about how to implement ICD-10 codes using DSM-5, see Using DSM-5 in the Transition to ICD-10.

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People With Schizophrenia May Be at Higher Risk of Developing Dementia

People with schizophrenia may be at a higher risk for dementia with an earlier age at onset than those without the condition, according to a study published last week in JAMA Psychiatry.

By some estimates people with schizophrenia will die, on average, 15 to 20 years earlier than the general population. Although schizophrenia is associated with several age-related disorders and considerable cognitive impairment, studies comparing the risk of dementia among people with schizophrenia versus those without have produced mixed results.

Using nationwide registers in Denmark, researchers from Aarhus University in Denmark and the University of Washington tracked the outcomes of more than 2.8 million people aged 50 and older—20,683 of whom had or developed schizophrenia over the course of the study—for up to 18 years. Overall, 136,012 individuals developed dementia, including 944 individuals with a history of schizophrenia.

After adjusting for age and sex, schizophrenia was found to be associated with a more than two-fold higher risk of dementia when compared with persons without schizophrenia. The relative risk of dementia was almost four-fold higher among individuals younger than 65 years. In absolute numbers, 7.4 of 100 people with schizophrenia developed dementia before the age of 80 years compared with 5.8 of 100 people without schizophrenia.

The risk of dementia in people with schizophrenia was only slightly reduced when adjusting for substance abuse disorder but was unaffected by adjustment for medical comorbidities including cardiovascular disease and diabetes.

“It is clear that individuals with schizophrenia develop dementia at a higher-than-expected rate and at younger ages than those without schizophrenia,” wrote Constantine Lyketsos, M.D., M.H.S., and Matthew Peters, M.D., both of Johns Hopkins University in a related editorial. Still, they noted, “[t]he majority do not undergo cognitive decline, suggesting that this heterogeneous syndrome belies a subgroup with a condition that is both neurodevelopmental and degenerative. … Focusing on the individuals who develop progressive dementia could be a successful approach that will provide clues to the etiology of this diverse condition.”

For related information, see the Psychiatric News article “Neuropsychiatric Symptoms Implicated in Conversion From MCI to Dementia.”

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Science Linking CTE, Depression, and Suicide Is Inconclusive, Researcher Says

Chronic traumatic encephalopathy (CTE) has been a medical concept for over 80 years. However, only in the past few years has suicidality been considered a common clinical feature of the disorder—a factor that has coincided with numerous media reports linking mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE.

In an article published today in the Journal of Neuropsychiatry and Clinical Neurosciences, Grant Iverson, Ph.D., of Harvard Medical School cautions that the science underlying the assertions linking CTE neuropathology, depression, and suicide is inconclusive.

“There has been an assumption in the literature (and the media) that the neuropathology of CTE causes depression and increases the risk for suicide in former athletes and military veterans. However, risk factors for suicide in former NFL players and other collision sport athletes should be considered in the broader context of the risk for suicide in the general population,” Iverson wrote.

The article outlines the diverse risk factors for depression and suicidality—including chronic pain, financial difficulties, and substance abuse—as well as evidence suggesting that many of the clinical features attributed to CTE are comorbid in men with depression who do not have a history of repetitive neurotrauma.

“It is important for health care providers to appreciate that there are multiple underlying biopsychosocial causes for mental health problems in former athletes—and these mental health problems might improve substantially with treatment,” Iverson wrote. “This reinforces the pressing need to provide evidence-based mental health treatment to those who are experiencing depression, substance abuse problems, and life stressors.”

For related information, see the Psychiatric News article “Suicide, Chronic Encephalopathy Link Questioned.”

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Levin Calls for Increased Access to Services on NDSD’s 25th Anniversary

In a blog post today, APA CEO and Medical Director Saul Levin, M.D., M.P.A., marked the 25th anniversary of National Depression Screening Day (NDSD) by calling for increased efforts to connect people with mental illness to the treatment they need.

National Depression Screening Day is an education and screening event conducted by hospitals, clinics, colleges, and community groups nationwide. The program provides free, anonymous screenings for depression, generalized anxiety disorder, bipolar disorder and posttraumatic stress disorder, as well as referral to treatment resources if warranted. According to the NDSD website, screenings are held both online and in-person and thousands of people participate each year.

“Even though most of us know someone who has experienced a mental health concern, the stigma associated with seeking mental health care is still a major barrier to treatment,” Levin wrote. “If the goal is to live in a world where mental health issues are viewed and treated with the same gravity as physical ailments, we will all need to work together to combat stigma and other barriers to treatment. That is why events like NDSD are so important, not just for raising awareness of this serious issue, but also because they help facilitate better access to treatment for those among us who need it most.”

Levin added, “Of course, creating awareness for mental health issues is not enough on its own. Community mental health programs need the support of national public health groups if true progress is to be made to ensure people with serious mental illness receive the help they sorely need.”

NDSD’s website features a free, anonymous screening tool and facts about symptoms of depression and other disorders, as well as facts about the connection between general medical and mental illness.

For more information on how to recognize symptoms of mental illness, as well as when and where to seek care, see Understanding Mental Disorders Your Guide to DSM-5.

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FDA Approves Aristada for the Treatment of Schizophrenia

The Food and Drug Administration on Monday approved Aristada (aripiprazole lauroxil), a long-acting injectable antipsychotic, for the treatment of schizophrenia. The medication requires administration by a health care professional every four to six weeks.

The approval of Aristada was based, in part, on the results of a 12-week clinical trial of 623 participants with schizophrenia who were experiencing an acute exacerbation. Participants were randomly assigned to receive a gluteal intramuscular injection of aripiprazole lauroxil (441 mg), aripiprazole lauroxil (882 mg), or matching placebo once monthly for 12 weeks.

Patients in the 441 mg and 882 mg aripiprazole lauroxil groups demonstrated greater improvements in total scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Improvement scale than those treated with placebo. The most common side effects reported by participants receiving the medication were insomnia, headaches, and akathisia.

“Long-acting medications to treat schizophrenia can improve the lives of patients,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the Center for Drug Evaluation and Research at the FDA. “Having a variety of treatment options and dosage forms available for patients with mental illness is important so that a treatment plan can be tailored to meet the patient’s needs.”

Similar to other atypical antipsychotics used to treat schizophrenia, Aristada comes with a Boxed Warning alerting health care professionals about an increased risk of death associated with off-label use of the medication to treat behavioral problems in older adults with dementia-related psychosis. To date, no atypical antipsychotic has been approved to treat dementia-related psychosis.

According to a press release by Alkermes Plc, the manufacturers of Aristada, the newly approved antipsychotic is being prepared to be launched “immediately.”

For related information on aripiprazole, see the Psychiatric News article “FDA To Review Application for Abilify Pill With Ingestible Tracking Device,” featured in most recent issue of PsychoPharm.

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Study Finds SGAs Do Not Substantively Increase Risk of Major Birth Defects

The use of second-generation antipsychotics (SGAs) during the first trimester does not appear to substantively increase the risk of major birth malformations, according to a report published today in AJP in Advance.

Given that discontinuation of medication during pregnancy can lead to relapse or worsening of illness in patients with psychiatric disorders, the results challenge the clinical practice of abruptly stopping maintenance treatment for psychiatric disorders during pregnancy, the study authors said.

Lee Cohen, M.D., of Massachusetts General Hospital along with researchers from several other institutions tracked the progress of 214 infants who were exposed to SGAs during the first trimester and a comparison group of 89 infants whose mothers had a history of psychiatric illness but who did not take SGAs during pregnancy. The women receiving SGAs were enrolled in the National Pregnancy Registry for Atypical Antipsychotics.

Three major malformations were identified among exposed infants. One infant had a transposition of the great arteries after first-trimester exposure to aripiprazole, quetiapine, bupropion, and labetalol. Another infant had a ventricular septal defect with surgical repair and had been exposed to ziprasidone, sertraline, and lamotrigine. Lastly, an imperforate hymen was identified in an infant exposed to aripiprazole, bupropion, and trihexyphenidyl. One major malformation was identified in the comparison group. The risk of major malformations reported in the exposed group was approximately two and a half times higher than in the unexposed group (6.2% versus 2.6%), although this was not statistically significant.

“Based on the 214 cases of first-trimester exposure to second-generation antipsychotics, it is reasonable to conclude that these agents as a class are not major teratogens,” the study authors wrote.

They concluded, “In summary, our results suggest that the use of a second-generation antipsychotic during the first trimester does not substantively increase the risk of major malformations. … [F]or women with substantial psychiatric morbidity and good response to a second-generation antipsychotic, maintenance treatment with a second-generation antipsychotic during pregnancy may be the most prudent treatment option, similar to recommendations for continued treatment for pregnant women with other serious and chronic medical conditions, such as epilepsy.”

AJP Editor Robert Freedman, M.D., added, “As a field, we have become aware that both psychiatric illness itself and the drugs used to treat it can adversely affect the outcome of pregnancy. Cohen and colleagues have performed a careful study of matched groups of pregnant women with mental illness—those treated with second-generation antipsychotics versus those treated with other medications. At this point, it is helpful to clinicians to know that no evidence for a particular adverse risk profile for second-generation antipsychotics has emerged.”

For related information, see the Psychiatric News article “Study Examines Association Between SSRIs, Birth Defect Risks.”

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Study Suggests Stimulants Are Safe, Effective for Treating ADHD in Youth With Heart Defects

Youth with attention-deficit/hyperactivity disorder (ADHD) and congenital heart disease may be able to safely take stimulant medications for their ADHD, so long as proper care and diligence is taken, according to research presented yesterday at the Society for Developmental and Behavioral Pediatrics Annual Meeting in Las Vegas.

A team of researchers from Cincinnati Children's Hospital Medical Center compared the health outcomes of 44 youth (aged 6 to 18) with congenital heart defects who were taking stimulants and found no increased risk for death or changes in cardiac vital signs, such as blood pressure or heart rate, when compared with youth with similar heart defects who were not taking stimulants. The youth taking stimulants also showed significant improvements in their ADHD symptoms.

“Children with congenital heart disease are at high risk for ADHD, but fears about cardiovascular side effects, including sudden death, limit the use of stimulant medications,” Julia Anixt, M.D., a developmental and behavioral pediatrician at Cincinnati Children's Hospital Medical Center, said in a press release. Since 2006, the Food and Drug Administration has required warning labels on stimulant medications that caution that they generally should not be used in patients with serious heart problems due to the increased risk of serious cardiovascular complications.

“This study indicates that stimulants are both effective and safe when prescribed with appropriate monitoring and in collaboration with the patient's cardiologist,” Anixt said.

For related information, see the Psychiatric News article “Pediatricians Urged to Adhere Better to ADHD Care Practices.”

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APA President Calls for Gun Control Measures in Wake of Oregon Tragedy

In a blog post today, APA President Renée Binder, M.D., called for the implementation of “common sense measures” to reduce access to firearms in this country. Her call to action came in response to the mass shooting on Thursday that took the lives of nine people at Umpqua Community College in Roseburg, Ore., as well as that of the 26-year-old gunman. Nine other people were wounded in the attack.

“As physicians,” she wrote, “we have the opportunity to educate our patients about the risks of keeping guns in the home particularly in the presence of children, adolescents, people with dementia, people with mental illnesses, including substance use disorders, who are at risk of harming themselves or others, and people who abuse children or partners. Currently, a number of states prevent physicians from asking questions about guns. This needs to be changed.”

Among the measures that APA supports are background checks and waiting periods before gun purchases, closing gun-show loopholes, product safety regulations, safe storage requirements, and gun-free college campuses and hospitals. Also, Binder noted that temporary firearm restraining orders could be one way to protect potential victims of these tragedies—family members and/or law enforcement could go before a judge and request that guns be temporarily removed from an individual who is likely to be dangerous toward himself and/or others.

To those who want to connect gun violence with mental illness, Binder emphasized that people with mental illness are far more likely to be victims of violence and that the majority of individuals with mental illness will never be violent toward others; the risk of self-harm is far greater. “Stronger indicators of risk include a history of violent behavior, domestic violence, and drug or alcohol abuse” she noted. “We urge states to develop new procedures for the temporary removal of access to guns during periods of elevated risk.”

Echoing President Obama in his address to the nation on Thursday, Binder said, “Our hopes and prayers will not be enough to stem the tide of gun violence in our country. We need decisive action in favor of responsible gun regulation. Until then, gun violence remains a significant threat to America’s public health, and as physicians, we have a vital role in advocating for change.”

For information on the response of the Oregon Psychiatric Physicians Association to the tragedy, see yesterday’s Psychiatric News Alert.

Oregon Psychiatrists Respond to Mass Shooting Incident

America’s latest mass shooting prompted a quick response from the Oregon Psychiatric Physicians Association (OPPA) to help survivors, families, and friends affected by the tragedy yesterday.

The incident took the lives of nine people at Umpqua Community College in Roseburg, Ore., as well as that of the 26-year-old gunman. Another seven people were wounded in the attack.

Dan Bristow, M.D., a psychiatrist with Kaiser Permanente in Portland, Ore., and the public information chair of the OPPA, emphasized the need to engage the news media to help educate the public about the psychological consequences to the community.

It is too soon to understand the motivations of the gunman, said Bristow. “This is a time to support, and be supported by, the ones we love—friends, family, neighbors, and fellow Oregonians.”

The OPPA posted messages on its website urging just that and suggesting ways that adults could discuss such traumatic events with children.

Bristow said he plans to travel to Roseburg, 180 miles south of Portland, later today to provide perspective on the event to local media and coordinate a longer-term response with area psychiatrists in that underserved area of the state.

The goal, he said, was to be attuned to the needs of the community and offer OPPA’s assistance as needed.

Look for a full report on the tragedy and OPPA's response in a future issue of Psychiatric News.

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Meta-Analysis Highlights Ketamine’s Rapid, Yet Transient Antidepressant Effect

Even as the excitement over the potential of ketamine and other NMDA receptor antagonists for antidepressant treatment has grown in recent years, there have been concerns that off-label clinical use of ketamine as a therapeutic agent may be outpacing scientific scrutiny. While the authors of a meta-analysis appearing today in the American Journal of Psychiatry report that current efficacy data suggest ketamine infusion provides a rapid therapeutic benefit for patients with depression, they caution that the fleeting nature of this therapeutic benefit combined with ketamine’s potential for abuse and neurotoxicity warrants further investigation.

For the study, researchers from the APA Task Force on Novel Biomarkers and Treatments scoured the literature for placebo-controlled, double-blind, randomized clinical trials examining ketamine and other NMDA antagonists in the treatment of depression.

The analysis of seven trials (encompassing 147 ketamine-treated participants) confirmed that a single intravenous infusion of ketamine consistently produced a rapid and robust antidepressant effect that peaked within 24 hours of administration, accompanied by brief psychotomimetic and dissociative effects. However, by day 7, these antidepressant effects were largely diminished. An additional five trials examining ketamine’s ability to augment electroconvulsive therapy (ECT) (89 ketamine-treated patients) revealed that ketamine accentuated the antidepressant effects of ECT following an initial treatment but not at the conclusion of the ECT treatment regimen.

The task force also analyzed the findings of several randomized, controlled trials of other NMDA antagonists, including lanicemine, memantine, and N₂O, and two partial agonists at the NMDA coagonist site, d-cycloserine and rapastinel. They found that while lanicemine, memantine, and N₂O—which bind to the receptor at the same site as ketamine—failed to consistently demonstrate efficacy, d-cycloserine and rapastinel significantly reduced depressive symptoms without psychotomimetic and dissociative effects.

“The results from existing NMDA receptor antagonist studies are decidedly mixed,” said D. Jeffrey Newport, M.D., M.S., M.Div., a professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine and member of the APA Task Force on Novel Biomarkers and Treatments. “Therapeutic response to ketamine is rapid and robust but fleeting at best. … Results with other NMDA antagonists have unfortunately been largely disappointing. Nevertheless, early experience with ketamine suggests that glutamatergic strategies for treating depression warrant further investigation,” he told Psychiatric News.

“Although the antidepressant effect of ketamine appears to be clear, it’s increasingly widespread use in the community is of concern for several reasons, including the virtual absence of any data on serial administration, dosing schedules, tachyphylaxis to the therapeutic effects, and need for cardiac monitoring during administration, as well as the concerns of abuse liability and neurotoxicity,” said Charles Nemeroff, M.D., Ph.D., the Leonard M. Miller Professor and Chairman of the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine and Task Force member. Additionally, Nemeroff told Psychiatric News, “The precise mechanism of action of ketamine’s antidepressant effect remains obscure.”

Nemeroff said the Task Force is working on developing recommendations for ketamine use. “This is important because of the unusual situation in which we find ourselves, namely a drug approved for one use by the FDA has found its way into the psychiatric pharmacopoeia without the usual high standards and wealth of data in large clinical studies required for FDA approval,” he said.

For related information, see the Psychiatric News article “The Ketamine Challenge: When Practice Leaps Ahead of Science.”

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