Study Compares Efficacy of Ketamine vs. Esketamine in Clinical Setting

Intravenous ketamine may improve patients’ depressive symptoms more rapidly than intranasal esketamine, according to a report in JAMA Psychiatry.

Sina Nikayin, M.D., of Yale University and colleagues reviewed medical data from adults with major depressive disorder who received ketamine or esketamine therapy at the Interventional Psychiatry Service at Yale New Haven Psychiatric Hospital between September 2016 and April 2021. The sample included 129 individuals who received ketamine (0.5 mg/kg over 40 minutes per session) and 81 who received esketamine (56 mg or 84 mg spray per session). The demographic characteristics of the two groups were similar: Patients were predominantly non-Hispanic White with private insurance.

After six treatments administered at least weekly, patients who received ketamine had lower average scores on both the clinician-administered Montgomery Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) compared with patients in the esketamine group. After a full course of treatment (up to eight treatments), QIDS-SR scores remained lower in the ketamine group; there was no statistical difference in MADRS scores between the two groups after eight treatments.

Patients in both groups also had statistically similar rates of treatment response (defined as 50% or greater improvement in MADRS scores), depression remission (MADRS scores of 10 or less), and suicidal ideation (score on MADRS question 10 or QIDS-SR question 12). Overall remission rates were 29.6% for patients taking ketamine and 24.0% for patients taking esketamine. Nikayin and colleagues noted these rates are lower than those reported in other studies, likely because the Yale Interventional Psychiatry Service is a tertiary referral center that treats the most severely ill patients.

“Although both treatments reduce symptoms, these findings signal a potential difference [for ketamine] that could be attributable to many factors, including dosing, delivery mechanism, role of arketamine [chemical mirror image of esketamine], or patient expectations,” the researchers wrote. “A randomized trial is needed to determine the comparative efficacy of these treatments.”

To read more on this topic, see the American Journal of Psychiatry article “Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation.”

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Driving Under the Influence Common Among People Who Use Methamphetamine, Cocaine

Nearly half of adults who have used methamphetamine during the last year have driven while under the influence, a study in Addictive Behaviors has found. The study also revealed that more than one-fifth of adults who have used cocaine in the last year have driven under the influence.

Trenette C. Goings, Ph.D., of the University of North Carolina at Chapel Hill and colleagues examined data from 170,944 adults aged 18 years and older who participated in the annual National Survey on Drug Use and Health between 2016 and 2019. As part of this survey, participants were asked if they had used cocaine or methamphetamine in the previous 12 months or driven under the influence of either of these substances in the previous 12 months.

Among those who reported using these substances in the previous 12 months, 47.2% who used methamphetamine and 21.6% who used cocaine reported driving under the influence in the same time frame, respectively.

“This is noteworthy given evidence suggesting cocaine-influenced driving … is considered to be more dangerous than [driving under the influence] of cannabis and comparable to driving with relatively low blood alcohol concentration,” the researchers wrote. “Moreover, methamphetamine-influenced driving … is understood as comparable to or more dangerous than driving beyond legal [blood alcohol content] limits.”

Among adults who reported past-year use of cocaine or methamphetamine, those who drove while under the influence were more than twice as likely to have also experienced a depressive episode or psychological distress in the past year compared with those who used the substances but did not drive under the influence.

“[T]his greater likelihood of depressive symptoms might relate to psychological distress as a potential driver of increased substance use, which in turn, places individuals at greater risk of [driving under the influence of stimulants],” Goings and colleagues wrote. “Alternatively, or as a complement, we know depression is not only a primary symptom of cocaine/methamphetamine withdrawal, but also increased risk for depression is a long-term consequence of stimulant use.”

For related information, see the chapter “Substance-Related and Addictive Disorders” in The American Psychiatric Association Publishing Textbook of Psychiatry, Seventh Edition.

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Youth Who Transition to Another Gender Not Likely to Transition Back, Study Finds

Youth who socially transition to a gender other than the sex they were assigned at birth are likely to continue identifying as that gender five years later, according to a study published in Pediatrics.

“These results suggest that retransitions are infrequent. More commonly, transgender youth who socially transitioned at early ages continued to identify that way,” wrote Kristina Olson, Ph.D., of Princeton University and colleagues. “Nonetheless, understanding retransitions is crucial for clinicians and families to help make them as smooth as possible for youth.”

Olson and colleagues used data from the Trans Youth Project, a longitudinal study involving 317 youth aged 3 to 12 years old. All participants were recruited between July 2013 and December 2017. Prior to joining the study, the youth had to have socially transitioned to a gender other than their sex assigned at birth—a process that typically involves changing their pronouns, first names, hairstyles, and clothing.

The authors used reports from youth and their parents to determine whether the youth retransitioned (meaning they transitioned again after their initial transitions) or if they continued to identify as their transitioned gender several years later. Participants were classified into three categories based on the pronouns they used: binary transgender (the child identified as the transitioned gender), nonbinary (the child used they/them pronouns), or cisgender (the child again identified as the sex they were assigned at birth).

An average of 5.37 years after their initial transitions, 94% of participants were living as binary transgender, 2.5% identified as cisgender, and 3.5% identified as nonbinary. The rate of retransitions among the participants was 7.3%, and four participants (1.3%) had retransitioned twice, to a nonbinary then back to transgender. Most retransitions occurred before the youth reached age 10. Youth who initially socially transitioned before age 6 were more likely to be living as cisgender five years later compared with youth who transitioned at age 6 or later.

Concerns that youth will experience regret after transitioning, particularly after starting hormone therapy, has led some physicians and even legislatures to question the ability of minors to consent to gender-affirming treatment, wrote Christina Roberts, M.D., M.P.H., of Children’s Mercy in Kansas City in an accompanying editorial. The “stability of transgender identity” five years after the initial transition, as evidenced in Olson’s study, should reassure physicians when recommending gender-affirming treatment, Roberts wrote.

She continued: “The low risk of regret should also inform the actions of legislators attempting to substitute their judgment for the judgment of patients, parents, and providers by denying transgender adolescents access to this evidence-based and potentially life-saving treatment.”

For related information, see the Psychiatric News articles “Record Number of Anti-Trans Bills Filed in States This Year” and “Psychiatrists Need to Prepare to Care for Gender-Variant Patients.”

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Alzheimer’s and Dementia Linked to Eight Modifiable Risk Factors

More than a third of all individuals with Alzheimer’s disease and related dementias living in the United States had one or more of eight modifiable risk factors, according to a report in JAMA Neurology.

The eight risk factors—midlife obesity, physical inactivity, low education, smoking, depression, diabetes, midlife hypertension, and hearing loss—were associated with 36.9% of Alzheimer’s and related dementia cases. The proportion of Alzheimer’s disease and related dementias associated with these risk factors was higher among men compared with women and among Black, American Indian and Alaska Native, and Hispanic individuals compared with White and Asian individuals.

“Policymakers and clinicians should … consider increasing efforts to prevent [Alzheimer’s disease and related dementias] by focusing on midlife obesity, physical inactivity, and low education, especially in higher-risk groups,” wrote Roch Nianogo, M.D., Ph.D., of the Fielding School of Public Health at the University of California, Los Angeles, and colleagues.

Nianogo and colleagues used the U.S. Behavioral Risk Factor Surveillance Survey (BRFSS) to look at the prevalence of the eight modifiable risk factors among 378,615 non-institutionalized individuals with Alzheimer’s and related dementias between January 2018 and December 2018. The BRFSS is a system of health-related telephone surveys that collect state data about U.S. residents regarding their health-related risk behaviors, chronic health conditions, and use of preventive services.

The researchers calculated population-attributable risk between the eight risk factors and Alzheimer’s disease and related dementias. Such “estimates take into account the strength of the association between the risk factor and the outcome as well as the prevalence of the risk factor,” they noted.

The most prominent risk factors among all participants were midlife obesity (17.7%), physical inactivity (11.8%), and low educational attainment (11.7%). The combined population-attributable risk was higher among men (35.9%) than women (30.1%); it was also higher among Black individuals (39.8%), American Indian and Alaska Native individuals (39.2%), and Hispanic individuals (34.2%) compared with White individuals (28.5%) and Asian individuals (15.8%).

“Understanding the sex-specific and race and ethnicity–specific associations with [Alzheimer’s disease and related dementias] burden may guide public health strategies,” Nianogo and colleagues concluded.

For related information, see the Psychiatric News article “Racial Disparities in Dementia Rate Linger.”

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COVID-19 Infection Less Likely in Hospitalized SMI Patients Prescribed Antipsychotics

Adults who are hospitalized with serious mental illness (SMI) and taking second-generation antipsychotics may be at lower risk of COVID-19 infection than those who do not take these medications, suggests a report in JAMA Network Open. In contrast, mood stabilizers may increase the risk of infection in this population.

“[T]o our knowledge, this is the largest study to systematically assess associations between the use of individual medications and the risk of COVID-19 infection among inpatients with serious mental illness,” wrote Katlyn Nemani, M.D., of the Nathan S. Kline Institute for Psychiatric Research in New York and colleagues.

Nemani and colleagues analyzed electronic health record data of adults aged 18 or older with serious mental illness who were treated at 18 psychiatric hospitals operated by the New York State Office of Mental Health. Beginning in March 2020, these hospitals started testing patients for COVID-19 and tracking their clinical status (for example, transfers to other facilities for COVID-19 treatment and COVID-19–related deaths).

The researchers focused specifically on 1,958 adults (average age 51.4 years) with schizophrenia, schizoaffective disorder, bipolar I disorder, or depression with psychotic features who were tested for COVID-19 and were continuously hospitalized from March 8, 2020, until medical discharge for COVID-19 or July 1, 2020. Patients were considered to have been exposed to a medication if it was prescribed before their COVID-19 test, used for at least seven days, and was administered on a schedule (as-needed medications were not considered for the analysis).

A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died, the authors noted. The patients prescribed second-generation antipsychotics (for example, olanzapine, clozapine, risperidone, aripiprazole, quetiapine, or paliperidone) were 38% less likely to test positive for COVID-19 than those not prescribed second-generation antipsychotics. In contrast, patients prescribed mood stabilizers (for example, valproic acid, lithium, or lamotrigine) were 23% more likely to test positive for COVID-19 than those who were not prescribed these medications.

After controlling for such characteristics as age, sex, medical risk factors, and exposure to other medications, the researchers found that the use of paliperidone remained significantly associated with decreased risk of infection (41% less likely) whereas use of valproic acid remained significantly associated with increased risk of infection (39% more likely). Clozapine was the only medication associated with decreased odds of mortality; however, this association did not remain statistically significant after adjusting for age, sex, and medical risk factors.

“Considering that antipsychotic drug classes notably differ in terms of adverse effect profiles and drug-drug interactions, this finding suggests that clinical surveillance may identify a major factor associated with the minimization of the potential adverse effects or drug-drug interactions,” wrote Benedetta Vai, Ph.D., and Mario Gennaro Mazza, M.D., both of IRCCS San Raffaele Scientific Institute, Milan, Italy, in an accompanying commentary. “Future studies considering outpatient clinical settings, as well as prospective cohort designs, are needed to confirm the potential protective role played by antipsychotics with regard to the risk of COVID-19 infection or the association of the use of antipsychotics with the risk of mortality, as well as the detrimental effect of valproic acid use.”

For related information, see the Psychiatric News article “Antidepressants May Reduce Severity of COVID-19.”

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FDA Clears Cerebrospinal Fluid Test to Help Diagnose Alzheimer’s Disease

Last week, the Food and Drug Administration (FDA) cleared for marketing the first biomarker-based diagnostic test for Alzheimer’s disease.

The Lumipulse G β-Amyloid Ratio (1-42/1-40) test, manufactured by Fugirebio Diagnostics Inc., measures two variants of the amyloid beta protein in cerebrospinal fluid. A positive result suggests that a patient may have amyloid plaques in the brain associated with Alzheimer’s disease. The cerebrospinal fluid is obtained through a spinal tap, which can usually be performed on an outpatient basis. Currently, amyloid plaques can be identified only with positron emission tomography (PET) brain scans, a process that can be time consuming and expensive.

“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” commented Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health, in a media release.

The Lumipulse test is intended for use in adults aged 55 years and older with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. According to the FDA, the Lumipulse test should not be used by itself to diagnose Alzheimer’s and should instead be used as part of a comprehensive evaluation. As noted by the FDA, amyloid plaques may be present in other neurological conditions as well as in some older patients who are cognitively healthy.

The FDA approved the Lumipulse test following a study of cerebrospinal fluid samples from 292 older adults participating in the Alzheimer’s Disease Neuroimaging Initiative. In this clinical study, 97% of adults with a positive Lumipulse test had amyloid plaques in their brains as confirmed by PET scan, while only 16% of adults with a negative Lumipulse test had confirmed amyloid plaques.

For related information, see the Psychiatric News article “Alzheimer’s Blood Test Shows Clinical Potential.”

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Nearly One-Fourth of Physicians in Large Academic Medical Center Experience Mistreatment

Nearly one-fourth of physicians who work at a large academic medical center have experienced mistreatment such as sexual harassment or abuse; verbal mistreatment or abuse; or physical intimidation, violence, or abuse on the job in the past 12 months, a study published today in JAMA Network Open has found. Patients and visitors were the most common source of mistreatment, followed by other physicians.

Susannah G. Rowe, M.D., M.P.H. of Boston Medical Center and colleagues analyzed data from 1,505 physicians at Stanford University School of Medicine who responded to a survey on workplace mistreatment and occupational well-being in September and October 2020. The survey included questions from the Professional Fulfillment Index, which measures employees’ intent to leave, and the Mistreatment, Protection, and Respect Measure, which measures respondents’ perceptions of protective factors in the workplace such as institutional systems that ensure employees are treated with respect and the presence of bystanders who speak up or intervene when they witness mistreatment or abuse.

Of 1,397 physicians who answered questions about mistreatment, 23.4% reported experiencing mistreatment in the last 12 months. Patients and visitors were the most common source of mistreatment, accounting for 70.9% of all mistreatment events as reported by 16.6% of physicians. Other physicians were the second most common source of mistreatment, reported by 7.1% of respondents.

Verbal mistreatment was the most frequent form of mistreatment, reported by 21.5% of physicians, followed by sexual harassment and physical intimidation, reported by 5.4% and 5.2% of respondents, respectively. Women were more than twice as likely as men to experience mistreatment, and multiracial and Black physicians were more likely than White and Asian physicians to report experiencing mistreatment.

Examples of mistreatment included complaints or criticisms related to professionalism, such as appearance or behavior; quality of work; sexual comments or jokes, inappropriate sexual attention, unwelcome advances, and requests for sexual favors; use of slurs, insulting jokes or humor, name-calling, swearing, yelling, intimidation, verbal attacks, nonphysical threats, warnings about retaliation; and pushing, shoving, and sexual or racial assault.

“Reducing mistreatment and enhancing protective systems has inherent ethical value, particularly considering that mistreatment is experienced inequitably based on race and gender,” Rowe and colleagues wrote. “Initiatives that prioritize reducing mistreatment of women and physicians of color can help reduce gender- and race-based workplace inequities, and thereby support greater racial and gender diversity among physicians.”

Physicians who perceived that there were no systems in place to protect against mistreatment had 711% higher odds of intending to leave, scored higher on measures of burnout, and scored lower on measures of professional fulfillment compared with those who believed such systems were in place. The researchers wrote that initiatives targeting mistreatment may result in benefits to patients, physicians, and health care organizations through reduction of burnout and its associated effects on care.

“These findings highlight the urgent need for organizations to put systems in place to reduce the incidence of mistreatment and for more research to determine which systems will be most effective,” the researchers concluded.

For related information, see the Psychiatric News article “Patient Characteristics Should Determine Response to Threatening Behavior.”

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