Friday, December 9, 2016

Gastrointestinal, Pulmonary Illnesses Top List in Hospitalized Patients on Clozapine, Study Finds


When prescribing clozapine—the only antipsychotic that has been FDA-approved for treatment-resistant schizophrenia—clinicians have been required by an FDA boxed warning to closely monitor patients’ blood to reduce the risk agranulocytosis and other adverse events. However, a study published in Psychosomatics now suggests pulmonary and gastrointestinal illnesses may be the most likely reason for patients prescribed clozapine to be hospitalized.

These findings are not unexpected, wrote Robert Morgan, M.D., Ph.D. (pictured above), and colleagues from the Mayo Clinic in Minnesota, “given that clozapine-related neutropenia and myocarditis have the highest incidence within several months after first exposure and are likely to be discovered through vigilant monitoring. Discovery then allows for early clozapine discontinuation and resolution of the adverse event, potentially avoiding medical hospitalization.”

The researchers conducted a retrospective chart review of patients with schizophrenia or schizoaffective disorder who were taking clozapine and admitted to an inpatient medical unit at the Mayo Clinic for nonpsychiatric illness between January 1, 2003, and August 1, 2005. A total of 104 adults aged 18 and older were included in the analysis. They were admitted into the hospital a total of 248 times, and the mean clozapine dose prescribed at the index admission was 407.2 mg.

Pulmonary illness and gastrointestinal illness were the most common reasons for hospitalizations at 32.2% and 19.8%, respectively. The most common pulmonary diagnosis was pneumonia, accounting for 58% of pulmonary admissions. The most common reason for gastrointestinal diagnosis was hypomotility, at 61.2%. The authors noted that clozapine was discontinued due to neutropenia in two patients; there were no patients admitted for myocarditis.

Psychiatric consultation was obtained in 25% of the hospitalizations, “most frequently for ‘clozapine management,’ retitration recommendations, or possible clozapine toxicity. Clozapine dosage adjustment infrequently occurred, and complete discontinuation was rare,” they wrote.

“While these findings are not indicative of causal relationships, an increased awareness of medical problems that lead to hospitalization in patients prescribed clozapine is required among all disciplines,” the authors concluded. 

For related information, see the Psychiatric News article “Why Won’t Clinicians Use Clozapine Despite Proven Superiority?” 

(Photo Courtesy of Mayo Clinic, Rochester)

Thursday, December 8, 2016

Depression Found to Be More Prevalent in Medical Students


A systematic review and meta-analysis published Tuesday in JAMA suggests that depressive symptoms may be more prevalent among medical students than others of similar age in the general population. The findings, which also revealed that a low percentage of these students seek care, point to the importance of identifying physicians at every stage of their career who are experiencing distress and helping them get the care that they may need.

For the report, Douglas Mata, M.D., M.P.H., of Harvard Medical School and colleagues analyzed 195 studies that reported on the prevalence of depression, depressive symptoms, or suicidal ideation in 129,123 medical students in 47 countries. 

According the analysis, 27.7% of students screened positive for depression—a percentage the authors noted is “higher than that reported in the general population.” A total of 11.1% reported suicidal ideation during medical school (prevalence estimates ranged from 7.4% to 24.2% depending on the screening instrument and cutoff score). Among the medical students who screened positive for depression, 15.7% reportedly sought psychiatric treatment, additional analysis revealed.

The authors outlined several limitations of the study, including the fact the analyzed data “were almost exclusively derived from self-report inventories of depressive symptoms that varied substantially in their sensitivity and specificity for diagnosing major depressive disorder.” Nonetheless, they wrote, “Combined with the finding that only 15.7% of medical students who screened positive for depression sought treatment, the high prevalence of suicidal ideation underscores the need for effective preventive efforts and increased access to care that accommodates the needs of medical students and the demands of their training.”

In September, APA President Maria A. Oquendo, M.D., Ph.D., wrote of the mental health challenges that some physicians face and the factors that may contribute to their hesitancy to seek mental health care in a Psychiatric News column. “[M]ost physicians have enormous personal strength, both emotional and intellectual ‘reserves.’ Accordingly, they often are able to compensate for the presence of psychiatric symptoms, which both makes it difficult to identify them so they can receive assistance and leads them to feel more isolated, since no one knows how they really feel,” she wrote.

In a related editorial also published Tuesday in JAMA, Stuart J. Slavin, M.D., M.Ed., of St. Louis University School of Medicine posed the following question in response to these and other findings: “What is it about the culture of medicine and of medical education that has allowed this problem to remain so long unaddressed and for studies of interventions to lag so far behind the number of studies of the nature of the problem?” 

The stigma surrounding mental illness and an environment that holds “the firm belief that more pressure, more hours, and more demands must lead to better educational outcomes” are two of several factors Slavin suggests may have led to “the delayed and until recently muted response to the long-standing problem of poor mental health of medical students.” 

Slavin concluded, “Medical schools need to step up to address the mental health crisis among medical students, and solutions cannot just come from the mental health side; the problem needs to be viewed as an environmental health issue.”

(Image: iStock/Wavebreakmedia)

Wednesday, December 7, 2016

Major Health Legislation Passes Final Hurdle


By a vote of 94-5, the U.S. Senate today passed the 21st Century Cures Act, one of whose goals is to improve and reform the American mental health system. The House passed the same legislation a week ago, and it now goes to the White House for President Barack Obama’s signature

“The bipartisan passage of the 21st Century Cures Act is an example of the progress we can make when people from both parties work together to improve the health of our families, friends, and neighbors,” said the president in a statement.

The bill includes elements of legislation previously put forth by Reps. Tim Murphy (R-Pa.) and Eddie Bernice Johnson (D-Texas) in the Helping Families in Mental Health Crisis Act, as well as provisions in the Mental Health Reform Act of 2016, sponsored by Sens. Chris Murphy (D-Conn.) and Bill Cassidy (R-La.)

APA noted its approval of the Senate action.

“This long-awaited and much-needed mental health reform will help to increase access to care and improve the quality of care for people with mental health and substance use disorders, especially for the 13 million Americans living with serious mental illness,” said APA President Maria A. Oquendo, M.D., Ph.D., in a statement. “The bill will toughen enforcement of existing parity laws, helping to ensure that mental health care services are covered just like other health care services.”

These are among the legislation's provisions:

  • Reauthorizing grants to support integrated care models so that mental health professionals can work more closely with primary care doctors.
  • Reauthorizing grants for training programs, such as the APA Foundation’s Typical or Troubled? program, which trains school officials to identify students in need of mental health services.
  • Requiring the Department of Health and Human Services to develop a plan to ensure enforcement of federal parity laws that mandate that insurers cover mental illness the same as any other disorder.
  • Providing $1 billion in state grants to address the opioid epidemic.

“We look forward to working with the administration and Congress to help ensure resources are available for full implementation,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A.

(Image: kropic1/shutterstock.com)

Tuesday, December 6, 2016

Expert Group Proposes Consensus Criteria for Determining Treatment-Resistant Schizophrenia


An international group of experts has proposed consensus criteria for determining when schizophrenia is “treatment resistant.” The criteria are described in a report appearing in AJP in Advance today.

More standardized criteria in clinical trials could aid in the development of better treatments for patients with refractory schizophrenia, according to the authors of the paper. 

The criteria were formed by the Treatment Response and Resistance in Psychosis (TRRIP) working group, an international group of more than 50 experts on schizophrenia and treatment resistance. The group performed a systematic review of definitions of treatment-resistant schizophrenia used in randomized antipsychotic clinical trials. They found wide variation in criteria that were used to define treatment resistance, particularly in the domains of symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies used the same criteria.

To address this variation, the working group developed “consensus criteria” specifying minimum and optimal criteria for each domain. A few of the domains and their optimal criteria for determining treatment resistance include the following: 
  • Symptom severity and change: Treatment-resistant patients’ symptoms should be at least moderately severe, as defined on a standardized rating scale such as the Positive and Negative Syndrome Scale. They should experience less than 20% symptom reduction, also using a standardized rating scale, during a prospective trial or observation of six or more weeks.
  • Functioning: Treatment-resistant patients should be determined to have at least moderate functional impairment, measured using a validated scale such as the Social and Occupational Functioning Scale.
  • Past treatment: Treatment-resistant patients should have experienced at least two past unsuccessful treatment episodes with different antipsychotic drugs, of at least six weeks duration at a therapeutic dosage for both trials.
  • Dosage: Treatment-resistant patients should have received a therapeutic dose in previous medication trials equivalent to at least 600 mg of chlorpromazine per day. 
“The management of treatment resistance remains a real clinical challenge,” John Kane, M.D. (pictured above), a co-chair of the working group, told Psychiatric News. “I think we need to focus a lot more of our research energy on how we can better serve those patients who don’t respond adequately to the medications we have. A key goal [of the proposed criteria] is to help advance efforts to provide help to these patients by conducting more and better designed research in those people who are treatment resistant.”

For related information, see the Psychiatric News article “Clozapine Use Varies From State to State.”

(Image: Courtesy of John Kane, M.D.)

Monday, December 5, 2016

Response to Initial rTMS for Depression Found to Predict Subsequent Response


Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe and effective treatment option for patients with treatment-resistant depression, but many patients fail to respond to the treatment or experience a relapse of symptoms. While some studies suggest the best strategy for sustaining the antidepressant effect of rTMS is regular maintenance sessions, others suggest offering the treatment only if relapse occurs (known as reintroduction of rTMS).

A study published in the Journal of Neuropsychiatry and Clinical Neurosciences in Advance has found that a patient’s response to rTMS the first time may predict how well he or she will respond to a subsequent session of rTMS. The study authors noted these findings support the use of rTMS reintroduction therapy for responders, which could potentially reduce the number of sessions that they might have otherwise received as part of maintenance therapy.

The findings arose from a retrospective chart review of 225 patients who received rTMS for treatment-resistant depression as a part of the clinical program at the Berenson-Allen Center or Noninvasive Brain Stimulation at Harvard Medical School from 2000 to 2015. Of this group, 18 patients met the criterion of having a reintroduction of TMS therapeutic strategy, though two were excluded for inadequate symptom data.

Ten of the 16 remaining patients were responders to the initial rTMS treatment (classified as at least a 50% reduction in Beck Depression Inventory [BDI] score), and eight of these 10 responders were also responders to reintroduction. Three patients who partially responded to the initial rTMS treatment (25-50% reduction in BDI) also responded to reintroduction rTMS.

There was also some correlation in the overall strength of response between sessions; that is, patients who had a strong improvement in depression symptoms after the initial session tended to have greater BDI reductions after the reintroduction session as well. The authors estimated that the magnitude of the initial response explains approximately one-third of the magnitude of subsequent response.

“Thus, other factors, either not evaluated in this study or requiring a larger sample size to achieve significance, such as gender, age, refractoriness, baseline severity, and comorbid disorders, could also have a significant predictive role,” they wrote. Nonetheless, the authors noted that the findings support “an approach involving watchful waiting and reintroduction of TMS when [responders] experience a relapse, thus placing rTMS as a viable long-term treatment regimen for treatment-resistant depression.”

For related information, see the Psychiatric News column “Neuromodulation May Benefit Patients With Varying Psychiatric Illnesses,” by Andrew Leuchter, M.D., director of the Neuromodulation Division at the Semel Institute for Neuroscience and Human Behavior at the Semel Institute for Neuroscience and Human Behavior at the David Geffen School of Medicine at the University of California, Los Angeles.

(Image: iStock/Henrik5000)

Friday, December 2, 2016

Court Ruling May Increase Role of Mental Health Professionals in Evaluating Gun Rights


This past September, the U.S. Circuit Court of Appeals for the Sixth Circuit ruled that a federal law permanently barring the sale of firearms to people who have been involuntarily hospitalized for a mental illness was unconstitutional. The case centered around a 74-year-old Michigan man named Clifford Tyler, who, in 2011 was denied from purchasing a gun after a background check revealed that 25 years earlier, distraught over an impending divorce, he had been committed to a psychiatric hospital.  

In a column published yesterday in Psychiatric Services in Advance, Paul Applebaum, M.D. (pictured above), the Elizabeth K. Dollard Professor of Psychiatry, Medicine, and Law at Columbia University, pointed out that this decision could impact mental health professionals and organizations that predominantly favor gun restrictions and a desire to reduce discrimination among people with mental illness. “There is likely … to be a certain amount of ambivalence about endorsing an approach that will restore gun access to at least some people with histories of involuntary hospitalization, even if doing so enhances the extent to which they are treated as ordinary members of society—otherwise an important goal,” he wrote.

“A parallel dilemma likely to arise in the wake of Tyler will be the demand for psychiatrists and psychologists to become involved in determining when it is safe to restore firearm access,” he continued. Understandably, there are concerns by clinicians of the liability, adverse publicity, and sanctions they could face should their decisions turn out to be wrong. 

“The decision in Tyler suggests that we may be moving toward more individualized determinations of risk for larger groups of people, for whom the predictors of violence are even less well specified. If that’s true, the odds are that mental health professionals will once again be asked to undertake that role,” he concluded.

For related information, see the Psychiatric News column “Psychiatrists Have a Role to Play in Latest Gun Law Debates” by APA President Maria A. Oquendo, M.D., Ph.D., and “APA Weighs In on Cases Where Law Intersects With Psychiatry.”

Thursday, December 1, 2016

House Passes Major Mental Health Legislation


The House of Representatives last night passed the 21st Century Cures Act by a vote of 392-26. This wide-ranging, $6 billion bipartisan health legislation includes significant mental health components and had the support of the Obama administration.

The new act embeds medical leadership in the Substance Abuse and Mental Health Services Administration (SAMHSA), improves how the federal government finances and manages evidence-based mental health services, promotes workforce development and integrated care, and toughens the enforcement of mental health parity.

“This legislation will greatly benefit our patients with mental illness and substance use disorders,” said APA President Maria A. Oquendo, M.D., Ph.D., in a statement. “The bill strengthens existing parity laws so that mental illness is treated just like any other illness, and it better coordinates the efforts of federal agencies responsible for treating mental illness.”

The bill incorporates elements of legislation previously put forth by Reps. Tim Murphy (R-Pa.; pictured above) and Eddie Bernice Johnson (D-Texas) in the Helping Families in Mental Health Crisis Act as well as provisions in the Mental Health Reform Act of 2016, sponsored by Sens. Chris Murphy (D-Conn.) and Bill Cassidy (R-La.)

These are some of the provisions that the legislation includes:

• Appointment of a chief medical officer at SAMHSA who must hold a medical degree and have experience treating patients with mental illness or substance use disorders.
• $1 billion in state grants to address the opioid epidemic.
• Grants for promoting integrated care models for primary care and behavioral health care services.
• Grants for training programs like as the APA Foundation’s Typical or Troubled? program, which trains school officials to identify students who may need mental health care.
• Request for “clarification” of the permitted uses and disclosures of health information covered by the Health Information Portability and Accountability Act.

“With the House passage, we urge the Senate to pass this important legislation before adjourning for the year,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “Our mental health system needs to be retooled to meet the growing demands of our patients.”

For more in Psychiatric News about mental health legislation, see “House Approves Comprehensive Mental Health Reform Bill.”
(Image: Aaron Levin/PN)






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