Friday, January 14, 2022

FDA Issues Warning About Dental Risk With Transmucosal Buprenorphine

The U.S. Food and Drug Administration (FDA) has issued a Drug Safety Communication about dental problems associated with the use of buprenorphine products that dissolve in the mouth (transmucosal) and is requiring that a new warning about the risk of dental problems be added to the prescribing information and patient medication guides for these products. The dental problems include tooth decay, cavities, dental abscesses/infection, tooth erosion, or tooth loss.

The warnings come after an FDA review of cases reported to the agency or published in the medical literature revealed 305 cases of dental problems, 131 of them classified as serious, among patients who take transmucosal buprenorphine. Most of the dental problems occurred in patients who used the medication to treat opioid use disorder (OUD), although 28 cases occurred in patients who used the medication to treat pain. The most common treatment for these dental problems was tooth extraction or removal, reported in 71 cases. Other cases involved root canals, dental surgery, or other procedures such as crowns and implants.

“It would be useful to learn more about these reports and understand what proportion of total people using these specific formulations may be affected,” said Smita Das, M.D., Ph.D., M.P.H., chair of APA’s Council on Addiction Psychiatry. She noted that 305 is a relatively low number of cases given the number of people who take transmucosal buprenorphine among the approximately 1.7 million people who use buprenorphine as prescribed.

“Of course, for those individuals who are affected by dental problems, the impact is certainly considerable in their daily lives,” Das said. “With any medication, if there is a risk, it is important to consider the likelihood of that risk and how that risk compares to the benefit. In the case of buprenorphine, it is a lifesaving medication for many people and a core part of treatment for opioid use disorder.”

The FDA Drug Safety Communication advises health care professionals to ask patients about their oral health history before prescribing treatment with a transmucosal formulation of buprenorphine and to refer patients to a dentist as soon as possible after starting treatment. Patients should be instructed to gently rinse their teeth and gums with water and swallow after the medication has completely dissolved, then wait at least an hour to brush their teeth. The FDA also cautions patients not to stop taking their medications without consulting a health care professional.

Miriam Delphin-Rittmon, Ph.D., assistant secretary for mental health and substance use and the head of the Substance Abuse and Mental Health Services Administration (SAMHSA), issued the following statement in response to the FDA guidance: “SAMHSA urges patients and providers to weigh the lifesaving benefits of buprenorphine with this identified risk in making decisions about starting and ongoing use of buprenorphine.” She added that SAMHSA supports the FDA’s recommendations regarding the steps patients can take to care for their teeth and minimize their risk.

(Image: iStock/AndreyPopov)

Public Health Emergency Again Extended

Today Health and Human Services Secretary Xavier Becerra extended the Public Health Emergency determination for an additional 90 days, effective January 16. This is the eighth such extension since the original declaration was issued at the start of the COVID-19 pandemic and is not expected to be the last.

Thursday, January 13, 2022

Absence of Mood Improvement in Two Weeks May Predict Failure to Respond to TMS

If patients with major depressive disorder (MDD) demonstrate only limited mood improvements after two weeks of repetitive transcranial magnetic stimulation (rTMS), it may be a sign their treatment plans should be adjusted, suggests a study published in Depression & Anxiety.

“Insurers typically approve 36 [rTMS] sessions for patients with MDD. ... It is imperative to maximize benefit from the finite number of treatments [that] most patients can access,” wrote Alex Mirman, M.D., of the UCLA Semel Institute for Neuroscience and Human Behavior and colleagues. “Early, accurate prediction of nonresponse could allow clinicians to change treatment approach, with potentially better outcomes.”

Researchers recruited 329 participants receiving six weeks of rTMS treatment for an episode of nonpsychotic MDD. All participants had a primary MDD diagnosis and previously tried at least three antidepressant trials without achieving adequate improvements. Participants received 30 rTMS treatment sessions over the six-week period. Symptoms were assessed at baseline, after one and two weeks, and at the end of treatment using the 30-item Inventory of Depressive Symptomatology Self Report (IDS-SR). In addition to the IDS-SR score, the researchers analyzed three symptom subscales: sleep, mood, and anxiety. Response to rTMS was defined as a decline in pre- to posttreatment IDS-SR scores of at least 50%.

In total, 94 of the participants responded to rTMS. After one week, improvement in the IDS-SR mood subscale was the only significant predictor of total IDS-SR improvement by the end of the study.

Participants with severe or very severe depression symptoms at the start of the study whose mood improved by less than 20% after one week were highly unlikely to show a response to rTMS by the end of the study. None of the 19 participants with very severe symptoms at baseline who failed to show any improvement in mood after two weeks reached the criteria for response by the end of the study. Lack of improvement in sleep at two weeks was also a significant predictor of nonresponse.

“Our prior work suggests that in subjects showing limited improvement after [two] weeks of treatment, changing rTMS approach improved outcomes,” the authors concluded. “Together, these studies provide a rationale for TMS clinicians to consider changing rTMS approach in people with severe baseline depression showing no mood improvements after one week. This approach could lessen the burden of futile treatment and optimize efficacy in those severely depressed individuals who have most to gain from rTMS.”

For related information, see the Psychiatric News article “New Stanford Protocol for TMS Found to Achieve Fast Remission.”

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Time to Vote in APA’s 2022 Election!

The voting period for APA’s 2022 election is now open. You can vote by using the emailed ballot you should have received by now or clicking on “Vote Today” on APA’s website. Take time to learn more about this year’s candidates by reading the Special Edition APA Election Newsletter and viewing the archived town halls in which candidates responded to key questions. The deadline to vote is January 31 at 11:59 p.m. ET. Your vote matters to the future of APA and psychiatry!

Wednesday, January 12, 2022

FDA Approves Novel Drug to Treat Insomnia

The U.S. Food and Drug Administration (FDA) has approved Quviviq (daridorexant) 25 mg and 50 mg for the treatment of adult patients with insomnia.

The FDA has recommended that Quviviq be classified as a controlled substance, and it is expected to be available to patients in May 2022, following scheduling by the U.S Drug Enforcement Administration, according to a media release by Idorsia Ltd, maker of Quviviq.

Unlike many insomnia medications that act to sedate the brain, Quviviq is a dual orexin receptor antagonist, which works to reduce overactive wakefulness.

The efficacy of Quviviq was evaluated in two multicenter, randomized, double-blind, placebo-controlled studies. A total of 1,854 adults with insomnia (as defined by DSM-5) were randomized to receive Quviviq or placebo once daily in the evening for three months. The first study included 930 adults randomized to Quviviq (50 mg or 25 mg) or placebo. The second study included 924 adults randomized to Quviviq (25 mg or 10 mg) or placebo.

In both trials, the researchers compared changes in Latency to Persistent Sleep (a measure of how long it takes to fall asleep) and Wake After Sleep Onset (a measure of sleep maintenance), as indicated by polysomnography in a sleep laboratory. The study participants also reported their total sleep times, based on their recordings in a sleep diary throughout the trial. Study participants who took Quviviq (25 and 50 mg) showed a statistically significant improvement over placebo on sleep maintenance and total time sleeping after taking the medication for one and three months. Study participants who took the 10 mg dose of did not show a statistically significant improvement over those who took placebo on either measure or on total sleep time.

According to the Quviviq label, several studies evaluated the abuse potential of the medication. One study of 63 recreational sedative drug users who were given a single dose of the medication revealed high “drug liking,” suggesting potential for abuse.

Philip R. Muskin, M.D., M.A., a professor of psychiatry at Columbia University Irving Medical Center and senior consultant in consultation-liaison psychiatry at New York-Presbyterian Hospital/Columbia University Irving Medical Center, said the new medication will be an effective addition to the tools available to treat patients with insomnia. “We certainly need new drugs for insomnia,” he told Psychiatric News. “It’s a very common problem, even among people who don’t meet DSM criteria for insomnia, and insomnia is a component of so many other psychiatric disorders—depression, anxiety, trauma, among others.”

He advised psychiatrists to be cautious about prescribing to patients with a history of addiction.

“No one drug works for everyone,” Muskin said. “Many of the existing drugs that sedate the brain help people fall asleep but don’t help them stay asleep. This new medication tunes down the biological signal in our brain to stay awake. There is a need for drugs that use a different mechanism of action than sedating the brain.”

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Tuesday, January 11, 2022

People With AUD May Benefit From Combination of Ketamine, Mindfulness Therapy

Treating people with alcohol use disorder (AUD) with a combination of ketamine and mindfulness-based therapy may lead to greater abstinence from alcohol than educating people with AUD about their disorder, suggests a report published today in AJP in Advance.

“The results showed that [three infusions of] ketamine increased the number of days abstinent from alcohol at three and six months compared with placebo,” wrote Meryem Grabski, Ph.D., and Amy McAndrew, Ph.D., of the University of Exeter and colleagues. “The greatest difference in percentage of days abstinent from alcohol was between patients given ketamine and therapy and those given placebo and education.”

The study included adults aged 18 to 65 years who met DSM-5 criteria for moderate to severe AUD or DSM-IV criteria for AUD and had been abstinent from alcohol for at least 24 hours. Individuals were excluded from the trial if they had uncontrolled hypertension, were taking antihypertensives or antidepressants, and/or had current suicidal ideation. Other exclusion criteria included a diagnosis of any current or past psychiatric disorder (except depression, anxiety, AUD, or alcohol dependence) or of substance dependence other than AUD or ever seeking professional help for dependence on an illicit substance.

Ninety-six adults with AUD (35 women; average age 44 years) were randomly assigned to one of four treatment groups: (1) ketamine and therapy, (2) ketamine and alcohol education, (3) saline (placebo) and therapy, and (4) saline and alcohol education. The participants were encouraged to attend 10 study visits.

Beginning at visit 2, all participants received either 90-minute therapy or alcohol-education sessions. The therapy sessions focused on relapse prevention, mindfulness, and the promotion of well-being. The alcohol education sessions focused on the biology of addiction and steps to improve and maintain a healthy lifestyle. Also beginning at visit 2 and repeated at visits 4 and 6, the participants received infusions of either ketamine or saline. All participants participated in therapy or alcohol-education sessions prior to receiving their infusion and 24 hours later for a total of seven sessions. On average, it took participants 190 days to complete the trial (from randomization to visit 10).

The participants reported on alcohol use at each study visit and wore alcohol-monitoring bracelets through the end of treatment (visit 8). After the alcohol-monitoring bracelets were removed, the participants were asked to record alcohol use in a diary until the end of the trial.

Participants in the ketamine group reported a significantly greater number of days abstinent from alcohol compared with those in the placebo group at six-month follow-up (mean difference=10.1%), with the greatest difference in the ketamine plus therapy group compared with the saline plus education group (mean difference=15.9%), Grabski, McAndrew, and colleagues reported. There was no significant difference in relapse (recurrent heavy alcohol use) at six months between the ketamine and placebo groups.

“This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at six-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment,” the authors concluded.

For related information, see the American Journal of Psychiatry article “A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial.”

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CMS Field Tests Psychiatry Cost Measures, Invites Comments

The Centers for Medicare & Medicaid Services (CMS) is conducting field testing for five episode-based cost measures for the Merit-based Incentive Payment System (MIPS). The goal is to collect feedback on these cost measures for major depressive disorder and psychoses/related conditions. Testing will include assessment of the measures’ importance, scientific acceptability, and clinical validity. Clinicians and clinician groups with at least 20 episodes for at least one measure will receive a Field Test Report with information about their cost performance; feedback will be used to consider potential measure refinements. Draft specifications for each measure are available on the CMS website. The field testing ends Thursday, February 25.

APA is interested in reviewing Field Test Reports with APA members to inform our feedback to CMS. If you have received a cost report and are open to discussing it with APA staff, please contact Andrew Lyzenga at Also, reach out if you have any questions, comments, or input on episode-based cost measures or the field testing process.

Monday, January 10, 2022

Failure to Respond to Antipsychotics Early May Predict Long-Term Outcomes in Youth With Psychosis

Adolescents with first-episode psychosis who do not respond to aripiprazole or quetiapine within four weeks appear unlikely to respond to the medications eight weeks later, reports a study in the Journal of the American Academy of Child and Adolescent Psychiatry.

“[Y]oung people with psychosis usually face years of psychiatric treatment, and pharmacotherapy is essential for recovery. Yet, antipsychotics should be administered with caution in adolescents due to an increased risk of side effects,” wrote Anne Katrine Pagsberg, M.D., Ph.D., of the University of Copenhagen, Denmark, and colleagues. “Being able to identify non-response early facilitates quicker decision-making to change treatment and, thus, diminishes the risk of prolonged exposure and adverse events associated with an ultimately ineffective medication.”

Pagsberg and colleagues analyzed data from the Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis (TEA) study, a 12-week randomized, controlled trial in Denmark that compared the efficacy of aripiprazole to extended-release quetiapine in 113 adolescents (under age 18) diagnosed with first-episode psychosis. The researchers examined whether adolescents’ response to their assigned antipsychotic at two and four weeks could predict their response to the medications at 12 weeks. Non-response at Weeks 2 and 4 was defined as <20% decrease in the 30-item Positive and Negative Symptom Scale (PANSS-30) total score; non-response at the end of the trial was defined as <50% decrease in PANSS-30 at week 12. The analysis included 84 adolescents who adhered to their medication for all 12 weeks of the trial.

The researchers found that adolescents who did not respond to their assigned antipsychotic at Weeks 2 and 4 were about 80% and 90% likely, respectively, to not respond to the medication by the end of the trial. When adjusting for other variables, they found that non-response at Week 4 remained a statistically significant predictor of future non-response. They also examined other cutoff ranges and found that using a <30% symptom reduction at Week 4 offered the best predictive value for non-response at Week 12.

There were no significant differences between the two medications in terms of early and long-term response rates.

“In youth with first-episode psychosis showing early non-response to aripiprazole or quetiapine-extended-release, switching antipsychotic drug should be considered,” Pagsberg and colleagues concluded.

For related information, see the American Journal of Psychiatry article “A Population-Based Cohort Study Examining the Incidence and Impact of Psychotic Experiences From Childhood to Adulthood, and Prediction of Psychotic Disorder.”

(Image: iStock/Tassii)

Time to Vote in APA’s 2022 Election!

The voting period for APA’s 2022 election is now open. You can vote by using the emailed ballot you should have received by now or clicking on “Vote Today” on APA’s website. Take time to learn more about this year’s candidates by reading the Special Edition APA Election Newsletter and viewing the archived town halls in which candidates responded to key questions. The deadline to vote is January 31 at 11:59 p.m. ET. Your vote matters to the future of APA and psychiatry!

Friday, January 7, 2022

Social Workers in Primary Care Practices Found to Increase Access to MH Care

Deploying behavioral health social workers in primary care settings can increase the likelihood that patients with depression or anxiety will receive treatment within 30 days of their diagnosis, a study published today in Psychiatric Services in Advance has found.

Elizabeth R. Pfoh, Ph.D., M.P.H., of the Cleveland Clinic’s Center for Value-Based Care Research and colleagues examined data from 68,659 adults who had at least one primary care visit between 2016 and 2019 and a new diagnosis of depression, anxiety, or both. Behavioral health social workers were deployed in 40 practices between 2017 and 2019. Patients were grouped according to whether they were diagnosed before or after the social workers were deployed. Patients were followed for 35 days after their diagnosis.

In May 2018, changes were made to the electronic health record (EHR) system enabling physicians to more easily refer patients to the behavioral health social workers, who would then call patients within seven days of receiving the referral. The social workers screened patients using tools such as the Patient Health Questionnaire-9 and asked patients about current substance use and anxiety as well as any history of psychiatric disorders. The social workers also offered community resources or referred patients to mental health professionals such as a psychiatrist, psychologist, or licensed independent social worker.

Compared with those diagnosed with depression or anxiety before the social workers began working with the primary care practices, patients diagnosed with depression or anxiety had the following:

  • 4.35 times the odds and 4.27 times the odds, respectively, of having a behavioral health visit within 30 days of diagnosis.
  • 5 times the odds of having a visit with a non-psychiatrist therapist.
  • 1.82 times and 1.58 times the odds, respectively, of having a visit with a psychiatrist.

“Other health systems that have advanced EHR systems should consider introducing social workers trained in behavioral health to triage patients receiving new diagnoses of depression, anxiety, or both and systematically link them to appropriate care,” Pfoh and colleagues concluded.

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Thursday, January 6, 2022

Biomarker May Predict Patient Response to Antidepressants

Researchers have identified a biomarker that may be capable of predicting within one week whether patients with major depressive disorder (MDD) will respond to antidepressants. The findings were published yesterday in Molecular Psychiatry.

For the small pilot study, Steven Targum, M.D., of Signant Health in Boston, Mark Rasenick, Ph.D., of the University of Illinois College of Medicine in Chicago, and colleagues analyzed how antidepressants impact the protein Gs alpha, which allows neurotransmitters to make the molecule adenylyl cyclase. Previous research has shown that adenylyl cyclase is low in patients with MDD because Gs alpha is predominantly stuck in membranes called lipid rafts. Antidepressants may be able to move Gs alpha out of those rafts, the authors wrote.

Targum, Rasenick, and colleagues analyzed data from a study at the Emory University School of Medicine involving 49 participants with MDD and no psychosis and 59 controls with no history of MDD; participants ranged in age from 30 to 64 years. They were screened using the 17-item Hamilton Rating Scale for Depression (HAM-D) and completed at least two visits with researchers, scheduled one week apart, at which blood draws occurred to assess Gs alpha.

Nineteen of the participants with MDD went on to complete six weeks of treatment with antidepressants. Blood was drawn from these participants a third time six weeks after initiating medication treatment. Eleven participants responded to the antidepressants (defined as ≥50% improvement on HAM-D score) after six weeks.

Analysis of the blood draws revealed that during the initial screening visit, participants with MDD had significantly lower adenylyl cyclase activity compared with healthy controls. At the third visit, participants who responded to their antidepressant treatment experienced significant increases in adenylyl cyclase compared with those who did not respond to the medications.

“What we have developed is a test that can not only indicate the presence of depression but … also indicate therapeutic response with a single biomarker, and that is something that has not existed to date,” Rasenick said in a University of Illinois at Chicago news release.

According to the release, the biomarker blood test could indicate if Gs alpha is out of the lipid raft within one week. “Because platelets turn over in one week, you would see a change in people who were going to get better,” Rasenick said.

For related information, see the Psychiatric News article “Blood May Hold Secret to Biomarkers for Depression.”

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The content of Psychiatric News does not necessarily reflect the views of APA or the editors. Unless so stated, neither Psychiatric News nor APA guarantees, warrants, or endorses information or advertising in this newspaper. Clinical opinions are not peer reviewed and thus should be independently verified.