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An analysis of medical data from nearly 6 million Danes also found that in most cases, random chance may dictate which disorder people with co-occurring illnesses will develop first.
Using the robust medical data available in Danish health registries, a team of researchers has developed the most comprehensive map of psychiatric comorbidity (the occurrence of more than one mental illness in an individual) to date.
The notion that a patient can have multiple mental illnesses is not new. Research has shown that similar disorders such as depression and anxiety often co-occur, due to both genetic and environmental factors. However, this new study, published January 16 in JAMA Psychiatry, has taken this knowledge to the next level.
The researchers found that psychiatric comorbidity is more widespread than previously appreciated and is not restricted to closely related psychiatric disorders. In addition, the study found psychiatric comorbidity is often bidirectional; for example, the risk of being diagnosed with major depression after an anxiety disorder is about the same as the risk of being diagnosed with an anxiety disorder after being diagnosed with depression.
Experts in addiction and in digital technology say the app for opioid use disorder is an exciting development, but it remains to be seen if the technology will be widely used.
The Food and Drug Administration (FDA) in December 2018 cleared for marketing a prescription smartphone application to help individuals being treated for opioid use disorder (OUD) stay in treatment and maintain their motivation to recover.
“The challenge will be to encourage providers and patients to incorporate this new technology into their treatment,” said John Renner, M.D., co-chair of the APA Council on Addiction Psychiatry.
Modeled on an app cleared by the FDA in 2017 for patients with alcohol, cocaine, marijuana, and stimulant substance use disorders, reSET-O is specifically tailored for patients with OUD. The reSET-O app is intended for use in combination with outpatient psychosocial treatment that also includes treatment with buprenorphine. The app is downloaded directly to a patient’s smartphone after the patient receives a prescription to do so from his or her physician.
It is possible that the new generation of medical students is attracted to a psychiatry that is now better integrated with the rest of medicine and that offers work-life balance.
The popularity of psychiatry as a specialty choice among medical school seniors—and competitiveness for residency slots—may be increasing, according to recent data from the National Resident Matching Program (NRMP).
Between 2014 and 2018, psychiatry residency programs saw a 65 percent increase in applications from U.S. seniors, said John Spollen, M.D., a professor of psychiatry at the University of Arkansas Medical School, who presented an analysis of the NRMP data at the September meeting of the Association for Academic Psychiatry in Milwaukee. Spollen’s analysis was part of a workshop at the meeting on “Evidence-based Recruitment and Advising for Future Psychiatrists.”
Meanwhile, the increase of senior applicants during the same period was just 8 percent. Moreover, in 2018 a total of 254 U.S. medical school seniors who applied to psychiatry did not match into any program.
“This year the rate for psychiatry [of unmatched applicants] was 13.7 percent, which was the highest among any specialty in medicine,” Spollen told Psychiatric News in an interview.
While the legislation expands treatment options for substance use disorder, a measure that would have improved information sharing about a patient’s substance use treatment was not included.
A bill passed last month by Congress takes important steps toward combating the opioid crisis with a broad range of treatment and prevention programs, APA said in a statement.
“Opioid use disorder has taken a heavy toll on the health and well-being of Americans,” said APA President Altha Stewart, M.D. “APA is grateful to see bipartisan support for increased access to treatment for substance use disorders [SUD], including expanded access to residential treatment and medication-assisted treatment.”
Passing the Senate 98-1, the opioid legislation—The SUPPORT for Patients and Communities Act (HR 6)—combines 70 separate bills from Republicans and Democrats into one package. As of press time, the legislation was awaiting President’s Trump signature.
Previous studies of ketamine have focused on glutamate, but the new finding showing activation of opioid receptors shows why repeated use of ketamine may produce tolerance and addiction.
The antidepressant effects of ketamine appear to depend on activation of the brain’s opioid receptors, underscoring the drug’s addictive potential, according to a report published this week in AJP in Advance.
Alan Schatzberg, M.D., says further research should elucidate the respective roles of opioid receptors in mediating ketamine’s antidepressant effects.
When 12 patients with treatment-resistant depression were treated with the opioid antagonist naltrexone before receiving an infusion of ketamine, the antidepressant effects of ketamine were dramatically diminished.
“The implications for future research and clinical use of ketamine are potentially profound,” senior author Alan Schatzberg, M.D., the Kenneth T. Norris, Jr., Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, told Psychiatric News. Schatzberg is a past president of APA. Dr. Schatzberg shares senior authorship of the paper with Carolyn Rodriguez, M.D., Ph.D., assistant professor of psychiatry at Stanford. Lead authors of the study were Nolan R. Williams, M.D., an assistant clinical professor of psychiatry at Stanford, and Boris Heifets, M.D., Ph.D., an assistant clinical professor of anesthesiology at Stanford.
Ketamine, which was approved as an anesthetic in 1970, has been the object of enormous interest in the last several years for its ability to rapidly reduce symptoms of depression and acute suicidality. Hundreds of ketamine infusion centers have sprung up around the country offering off-label treatment for mood disorders.
While digital psychiatry and mental health apps are proliferating, experts caution that they may create new legal responsibilities and question whether the hype is getting ahead of evidence supporting their use.
A smartphone app now in development monitors a person’s voice frequency and detects when mania or depression is creeping in. Another prompts patients to take daily mental health assessments and sends a report to their psychiatrist, including whether they’re feeling suicidal. Yet another encourages people to adopt mindfulness practices as they go about their day.
These are just a few examples of digital psychiatry apps that were discussed at a packed session at APA’s 2018 Annual Meeting in May. Increasingly, patients are picking from among the thousands of mental health apps now available and downloading them onto smartphones, tablets, or computers. Clinicians, too, are encouraging patients to use them in between sessions and might even be uploading symptom data from patients, according to John Torous, M.D., director of the Division of Digital Psychiatry at Beth Israel Deaconess Medical Center in Boston. He is also a member of APA’s Committee on Mental Health Information Technology and chair of the Smartphone App Evaluation Work Group.
With smartphones available for as little as $50 at big-box retailers, virtually everyone can have access to digital psychiatry tools, Torous said. One type of app is a “symptom tracker,” which prompts people to enter their subjective experience of their mental health throughout the day or week. Other apps use sensors or smartphone hardware to capture “passive” data, such as how many hours a user has slept or how much a person has moved and where he or she has traveled using geolocation. Thousands of “interventional” apps, too, promise to coach users to better mental health.
What’s unique about digital psychiatry apps is the ease with which they allow physicians to access data, the volume of data generated, and the length of time that the data are retained, said former APA President Paul Appelbaum, M.D., the Dollard Professor of Psychiatry, Medicine, and Law at Columbia University College of Physicians and Surgeons. “They can also provide new types of information we’ve never had access to before, like where your patients are at every moment in time or what their voice tells you at any point in time,” he said.
Apps may be able to capture other important data that a clinician cannot, in part because people tend to report symptoms at a higher severity to an app than they do a physician, Torous said. In one recent study of which he was a co-author, patients reported suicidal ideation at a much higher rate—and had far worse depression scores via the app—than when they were with the clinician during check-ins. One theory: “It may be easier to tell some things to a cell phone than a person,” Torous said, adding that more research is needed to understand this phenomenon.
After much time and investment, several new classes of antidepressants may soon be available.
When ketamine was found to exert a rapid antidepressant effect by researchers at the National Institute of Mental Health (NIMH) more than a decade ago, it sparked hope for a new generation of treatments for depressive disorders. Now, new drug candidates are finally edging toward the finish line.
Esketamine nasal spray, an isomer of ketamine and antagonist to the N-methyl-D-aspartate (NMDA) receptor, may be the closest to reaching clinics. Just last month, Janssen Pharmaceutical Companies of Johnson & Johnson announced the company had submitted a new drug application (NDA) to the Food and Drug Administration (FDA) seeking approval of esketamine nasal spray for treatment-resistant depression in adults.
According to the press release by Janssen, the NDA is based on five pivotal phase 3 studies of esketamine nasal spray in patients with treatment-resistant depression: three short-term studies, one withdrawal maintenance-of-effect study, and one long-term safety study up to a year.
The results of two phase 3 trials of esketamine were presented at the APA Annual Meeting in May. In one trial, patients who failed to respond to at least two antidepressants during the current episode of depression were randomized to two treatments: esketamine nasal spray (56 mg or 84 mg) plus a new antidepressant or placebo nasal spray plus a new antidepressant. Patients who received esketamine experienced a statistically significantly greater drop on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28 compared with placebo. In patients 65 years and older with treatment-resistant depression, esketamine missed the primary efficacy endpoint in a phase 3 trial.
In the clinical trials, esketamine treatment was linked to side effects such as dizziness, nausea, increased blood pressure, and dissociation, which are similar to the side effects of ketamine.
Other NMDA receptor antagonists are also making their way through clinical development, including rapastinel (previously known as GLYX-13) and AGN-241741. Both molecules were developed by Naurex Inc. and recently acquired by Allergan. Rapastinel is purported to exert a rapid antidepressant effect, like ketamine, without the dissociative side effects. Several phase 3 trials of rapastinel as an adjunctive treatment and as monotherapy in major depressive disorder are currently ongoing. AGN241741 is being tested in phase 2 trials.
Another NMDA receptor antagonist, dextromethorphan, is combined with bupropion in a product known as AXS-05. In addition to its known effectiveness as an antidepressant, bupropion inhibits the metabolism of dextromethorphan by liver enzymes, so that dextromethorphan may accumulate in the body and reach therapeutic levels. AXS-05 is currently in phase 3 trials for treatment-resistant depression and for agitation associated with Alzheimer disease.