Valbenazine Significantly Improves Tardive Dyskinesia in Older Adults Over Long-Term

Adults ages 65 and older with tardive dyskinesia (TD) given valbenazine for up to 48 weeks experienced substantial and sustained improvements in symptoms while maintaining psychiatric stability, according to a post-hoc analysis of two clinical trials issued by the Journal of Clinical Psychiatry.

Valbenazine may be well suited for older patients with TD because it requires no titration to reach an effective, tolerable dose and is available as a sprinkle formulation that can be mixed with soft foods, noted Martha Sajatovic, M.D., of Case Western Reserve University School of Medicine in Cleveland, and colleagues. The researchers wrote that they undertook the study to address the “relative paucity of information on valbenazine efficacy and safety in relation to increasing age” among individuals 65 and older. The study was funded by valbenazine drugmaker Neurocrine Biosciences.

Sajatovic and colleagues pooled data from 304 individuals (55 of whom were 65 or older) who had participated in one of two 48-week studies of valbenazine—one an open-label study and the other a blinded-dosing study comparing 40 mg or 80 mg dosing. Participants were assessed with two clinician-rated assessments, the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), at baseline and at various points over 48 weeks.

Overall, 40% of older participants experienced a meaningful response to valbenazine (≥50% improvement in AIMS) at eight weeks, which rose to 65% at 24 weeks and 82% at 48 weeks; the improvements in older adults were comparable to those seen in younger participants. Similar strong and comparable improvements were seen with CGI-TD scores; in fact, at week 48, older adults were significantly more likely to have a CGI-TD score ≤2 than younger participants (93% versus 77% respectively).

There was no statistical difference in the prevalence of adverse events between younger and older participants, though a significantly higher percentage of older participants discontinued medication due to an adverse event compared with the younger subgroup (26% versus 13%, respectively). The most common adverse events were urinary tract infection, drowsiness, and headache.

“This article reports on data indicating that once-daily valbenazine is effective and well-tolerated in the ≥65-year age group,” the researchers wrote. “Given the projected rates of population aging in the U.S. and globally, along with the increased risk of TD with older age and historic under representation of adults aged ≥65 years in clinical trials, these results address an important gap in TD research.”

For more information, see the Psychiatric News article “Tardive Dyskinesia: Assessing and Treating a Debilitating Side Effect of Prolonged Antipsychotic Exposure.”

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Study Highlights Rising Number of Older U.S. Men Dying by Suicide

Suicide rates among men aged 65 years and older in the United States have been steadily rising since 2007, according to a study in the American Journal of Preventive Medicine. The report revealed that men who are White, aged 85 years or older, and living in rural areas may be at greatest risk.

Sanae El Ibrahimi, Ph.D., of the University of Nevada and colleagues analyzed suicide data from 1999 to 2018 reported to the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. The authors analyzed the data according to age group (65 to 74, 75 to 84, and ≥85 years), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic American Indian/Alaska Native, and Asian/Pacific Islander), methods of suicide, and the urbanization level (from rural to large metropolitan) of the county where decedents resided.

From 1999 to 2018, 106,861 men aged ≥65 years died of suicide in the United States—an age-adjusted rate of 31.4 per 100,000 people. While the data revealed that suicide rates fell annually by about 1.8% from 1999 to 2007, the rates rose steadily by 1.7% a year for the next decade.

“There are many potential contributors to the … shift [in suicide rates] around 2007, one of which could [have been] the start of the economic recession (i.e., the Great Recession) in the United States,” El Ibrahimi and colleagues wrote. “On the basis of their limited earning potential and high rates of unemployment, older adults may be left with fewer alternatives to supplement income, remain in their homes, be more socially isolated, and avoid associated hardships.”

Additional analysis revealed that the rate of suicide among men older than 85 years (48.8 per 100,000 people) was almost double the rate among those aged 65 to 74 years (24.7 per 100,000 people). Within the racial/ethnic groups, the lowest suicide rates were observed among men who were Black, with low variation across the urbanization levels (between 9 and 11 per 100,000 people), whereas the highest rate was observed among men who were White residing in the most rural communities (41.4 per 100,000 people).

The distribution of suicide by urbanization level and methods of suicide showed a higher rate of suicide by firearms in more rural than in more urban areas (34.8 per 100,000 in the most rural counties versus 19.2 per 100,000 in large central metropolitan counties).

“As the number of older people increases in the United States, the number of suicides by older people is also expected to increase,” El Ibrahimi and colleagues wrote. “Specific interventions are needed to change the existing trends in suicide prevalence among [older] male adults.”

For related information, see the Psychiatric News article “Psychoanalyst Examines How Culture Influences Suicide.”

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Isolation Puts Seniors With Substance Use Disorders at Heightened Risk During COVID-19

The social distancing and stay-at-home orders of the COVID-19 pandemic may present a challenge for people with substance use disorders by triggering anxiety, depression, or the urge to take drugs or drink alcohol. For people ages 65 or older, a population already vulnerable to the mental health effects of isolation, sequestering may be disproportionately burdensome.

“As long as social distancing guidelines remain in place, older adults in recovery from substance use disorders may find themselves cut off from support if they are unable to effectively use online treatment and self-help resources,” wrote Derek D. Satre, Ph.D., of the University of California, San Francisco, and Kaiser Permanente and colleagues in an article in the American Journal of Geriatric Psychiatry.

In the article, Satre and colleagues outlined key areas of concern for mental health professionals who work with seniors and offer guidance on how to help older patients.

Alcohol. Alcohol use can impair the immune system and increase susceptibility to pneumonia and other infectious diseases. Minimizing alcohol consumption may be critical for seniors during the pandemic, the authors wrote. They encourage mental health professionals to ask about their senior patients’ drinking habits and any recent increases in drinking that may stem from causes such as social isolation, financial stressors, anxiety, depression, or thoughts of suicide. The authors noted that pharmacologic treatments for alcohol use disorders such as naltrexone and brief behavioral interventions such as motivational interviewing can be incorporated into care, including care provided through telemedicine.

Tobacco and cannabis. Satre and colleagues noted evidence that smoking tobacco raises the risk of more severe COVID-19–related symptoms and that vaping nicotine “may damage lungs in ways that make users especially vulnerable to COVID-19–related symptoms.” They wrote that patients should be encouraged to use nicotine replacement products such as patches or gum or take anti-craving medications such as bupropion. They added that patients who use cannabis should use edible forms rather than smoke or vape.

Prescription opioids and benzodiazepines. Social distancing and quarantine may interrupt care for people with opioid use disorder and decrease their access to medication treatment, they wrote. “Lack of treatment access, in combination with social isolation, increases vulnerability to relapse and overdose for older adults during the pandemic.”

Satre and colleagues noted that although there are no published data regarding changes in benzodiazepine prescription rates associated with the pandemic, previous research has shown increased use associated with “disaster situations.” They added that the American Geriatrics Society Beers Criteria strongly recommends avoiding benzodiazepine use in seniors except in specific circumstances such as alcohol withdrawal because of the risk of cognitive impairment, falls, fractures, delirium, and other serious adverse events.

“Risks to older adults can be addressed by helping to expand access to interventions and by incorporating the assistance of partners, family, and caregivers in helping older patients use healthier coping techniques to manage stress as the pandemic continues,” they concluded.

For related information, see the Psychiatric News article “SAMHSA Issues Guidance on OUD Treatment During COVID-19.”

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Join Us for APA’s Spring Highlights Meeting This Weekend

APA’s free, live virtual Spring Highlights Meeting is just days away. Join psychiatry’s foremost experts and leaders this Saturday and Sunday, April 25 and 26, for discussions about physician leadership in a time of crisis, challenges and opportunities in research, and more. Participants in the free Spring Highlights Meeting can claim up to 10 AMA PRA Category 1 Credits and 8 hours of MOC Part 2 Credit but must register to claim credit.

Study Examines Efficacy of Esketamine-Antidepressant Combo in Older Adults With Treatment-Resistant Depression

A subset of individuals 65 years or older with treatment-resistant depression who took a new oral antidepressant plus intranasal esketamine showed greater improvement of symptoms than those who took an antidepressant and intranasal placebo, according to a report in the American Journal of Geriatric Psychiatry. However, the overall difference between the esketamine and placebo groups in symptom score reduction was not statistically significant, indicating a need for further research, wrote lead author Rachel Ochs-Ross, M.D., of Janssen Research & Development and colleagues.

The study was funded by Janssen, who markets intranasal esketamine. (The drug was approved by the Food and Drug Administration earlier this year for treatment-resistant depression.)

The researchers randomly assigned 138 patients 65 years or older with treatment-resistant depression to take intranasal esketamine or placebo twice weekly in addition to a new oral antidepressant daily for four weeks. Patients initially received 28 mg of esketamine or the placebo nasal spray, but the investigators increased the esketamine dose to 56 mg or 84 mg based on the patients’ response to the treatment. The primary endpoint was change in the Montgomery- Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Secondary measures included the percentage of patients who showed a treatment response (defined as a 50% or greater reduction in MADRS score) and rates of remission (defined as a MADRS score of 12 or less).

The average change in MADRS score for patients taking antidepressant plus esketamine was 10 points compared with 6.3 for patients taking antidepressant plus placebo. Treatment response was observed in 27% of patients receiving esketamine and 13.3% receiving placebo. Remission rates were 17.5% in the esketamine group and 6.7% in the placebo group.

The difference between the esketamine and placebo groups on the primary endpoint of overall symptom reduction was not statistically significant. This failure to achieve statistical significance may be related to lower dosing required in older patients and a need for longer treatment duration, the researchers wrote.

Additional analysis revealed that there was a greater reduction in total symptom scores among individuals aged 65 to 74 treated with esketamine compared with placebo that was not observed in patients aged 75 years or older, suggesting that the combination may benefit a younger subset of seniors.

“Given the need for treatments for [treatment-resistant depression in older adults] and the potential role of esketamine, future studies are needed to establish if esketamine is effective in [treatment-resistant depression in older adults] and if so the optimal induction/optimization/maintenance dosing and duration of treatment,” Helen Lavretsky, M.D., M.S., of the Semel Institute for Neuroscience and Human Behavior at UCLA and Steven P. Roose, M.D., of New York State Psychiatric Institute, wrote in an accompanying editorial. “There is much work to do but the exciting news is that studies are underway and hopefully new esketamine studies will be initiated that will provide the clinician with the information necessary to alter the deleterious trajectory associated with this high-risk population and difficult to treat population,” they wrote.

For related information, see the Psychiatric News article “Esketamine Approved For Treatment-Resistant Depression.”

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Playing Video Games May Increases Cognitive Control in Seniors, Study Finds

While studies have pointed to negative consequences of children’s excessive video-game playing, when adults try their hand at these games, it may increase their cognitive control, according to a Nature study featured in "Journal Digest" in today's  Psychiatric News.

Researchers at the University of California, San Francisco, created a 3-D racecar video game that measured cognitive control in adults who were instructed to notice specific road signs while driving full speed—virtually. After one month of video-game participation, adults aged 60 to 85 were evaluated for alterations in multitasking, working memory, and attention sustainment. Results showed that multitasking capabilities, working memory, and attention sustainment were dramatically increased and sustained six months after the video-game training. In addition, multitasking capabilities of seniors surpassed that of young adults who played the game for the first time.

The authors noted that this is the first study to show how custom-designed video games can be used to assess cognitive abilities across the lifespan. If the research is replicated, this could be a beneficial application to other brain-related disorders such as attention-deficit/hyperactivity disorder, depression, and dementia, which are also associated with deficits in cognitive control, the authors concluded.

To read more about emerging therapies for cognitive disorders and factors that may contribute to cognitive disorders, see the Psychiatric News articles "New Target Emerges in Search for Alzheimer’s Treatment" "Hearing Loss in Seniors Linked to Cognitive Decline."

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NIH Updates Consumers on Often-Overlooked Health Issue

Data from national surveys reveal a disturbing trend for 50- to 59-year-olds: the number of those reporting past-month abuse of illicit drugs—including nonmedical use of prescription drugs—more than doubled from 2002 to 2010, going from 907,000 to 2,375,000, or from 2.7 to 5.8 percent of this population. Among those 65 and older, 414,000 used illicit drugs in 2010. A new report, Prescription and Illicit Drug Abuse, available on NIHSeniorHealth.gov, describes this trend and the effects of medication and drug abuse on older adults.

According to the National Institute on Drug Abuse (NIDA), the numbers of older substance abusers may continue to rise, due to aging of the baby boomers, who were more likely than previous generations to have used illicit drugs in their youth.

Although substance abuse by older adults is preventable and treatable, many may not get the help they need because some common warning signs of abuse, such as sleep problems, falls, and depression, can also be signs of other health conditions. The new topic on "NIHSeniorHealth" provides tips on behaviors to watch for and appropriate steps to take if a substance abuse problem is suspected. "This topic is an excellent, easy-to-understand overview of a growing problem," said NIDA Director Nora Volkow, M.D. "It's a must-read for anyone concerned about substance abuse in themselves, an older relative or friend."

To read more details about the epidemic of prescription painkiller use, see Psychiatric News, here.

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