Disruptions TOPLINE: US adults with psychiatric illness experienced fewer disruptions in receiving psychotherapy following the transition to virtual psychiatric care that accompanied the onset of the COVID-19 pandemic, a large study has shown. METHODOLOGY: Retrospective study using electronic health records and insurance claims data from three large US health systems. Sample included 110,089 patients with mental health conditions who attended at least two psychotherapy visits during the 9 months before and 9 months after the onset of COVID-19, defined in this study as March 14, 2020. Outcome was disruption in psychotherapy, defined as a gap of more than 45 days between visits. TAKEAWAY: Before the pandemic, 96.9% of psychotherapy visits were in person and 35.4% were followed by a gap of more than 45 days. After the onset of the pandemic, more than half of visits (51.8%) were virtual, and only 17.9% were followed by a gap of more than 45 days. Prior to the pandemic, the median time between visits was 27 days and after the pandemic it dropped to 14 days, suggesting individuals were more likely to return for additional psychotherapy after the widespread shift to virtual care. Over the entire study period, individuals with depressive, anxiety, or bipolar disorders were more likely to maintain consistent psychotherapy visits, whereas those with schizophrenia, ADHD, autism, conduct or disruptive disorders, dementia, or personality disorders were more likely to have a disruption in their visits. IN PRACTICE: "These findings support continued use of virtual psychotherapy as an option for care when appropriate infrastructure is in place. In addition, these findings support the continuation of policies that provide access to and coverage for virtual psychotherapy," the authors write. SOURCE: The study, led by Brian K. Ahmedani, PhD, with the Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, Michigan, was published online October 11 in Psychiatric Services. LIMITATIONS: The study was conducted in three large health systems with virtual care infrastructure already in place. Researchers did not examine use of virtual care for medication management or for types of care other than psychotherapy, which may present different challenges. DISCLOSURES: The study was supported by the National Institute of Mental Health. The authors have no relevant disclosures. Related topic: Telehealth What Happens When There Is No Help?

GLP-1 Agonists and Suicide Risk A statement from the European Medicines Agency (EMA) about semaglutide and, more generally, glucagon-like peptide 1 (GLP-1) agonists recently caused a stir. Could these medicines lead to patients taking their own lives? Medical Authorities Alert The EMA published a press release in early July 2023 to announce that a review is underway after reports from the Icelandic Medicines Agency about two cases of patients who developed suicidal thoughts while taking liraglutide (Saxenda) and semaglutide (Ozempic). There was also a report of self-injury in a patient taking liraglutide. Clearly, a few cases aren't enough to call an entire therapeutic class into question or to establish contraindications. Further investigation is needed, and the European authorities who collected the data are analyzing the approximately 150 reports concerning possible cases of self-injury and suicidal thoughts in patients taking these drugs. We should have some results and answers by November 2023. This alert comes at a time when GLP-1 agonists, especially semaglutide, are being misused, particularly in France. The French health authorities (ANSM) have published a press release and reiterated that these medicinal products should be used only as indicated. Despite these warnings, alerts, and suspicions, the risk profile of GLP-1 agonists appears to clinicians to be very good. Although nausea and vomiting occasionally lead patients to stop treatment, there are no obvious major side effects. A risk for acute pancreatitis (though not yet fully confirmed) has been mentioned, as has a risk for thyroid cancer that has not fully been proven in humans. Do we now have to worry about suicide risk? Another Rimonabant Fiasco? This situation is reminiscent of what happened with rimonabant (Acomplia), which was studied and marketed in the early 2000s. Relatively soon after it reached the market, it was withdrawn, mainly because of a risk for depression and suicide. Is this a case of history repeating itself? Have we found ourselves in the same situation? Frankly, as it stands, I don't think so. It's true that with rimonabant, we had some worrying data that had already been observed in randomized clinical trials. There were already signs of mood disturbances in patients taking the drug vs placebo. With GLP-1 agonists, to my knowledge, there have been no reports of this kind in the clinical trials conducted. Of course, this doesn't rule out a rare risk. That's why we need to continue with the investigations. We also know that there are GLP-1 receptors in the central nervous system. We often talk about them as being located in the hypothalamus, which largely explains the effect of these drugs on appetite. But the mechanisms of action of GLP-1 agonists and medicines conventionally used to reduce appetite (anorectics or even rimonabant) are very different. This is why we don't really expect there to be any psychological side effects with GLP-1 agonists. What's the Explanation? Why do we have these suspicious observations of suicidal ideation or self-injury? What are the possible explanations? In my opinion, we must first confirm that the incidence of these psychiatric disturbances is greater in patients taking GLP-1 agonists than in a similar matched general population group. We should also question whether these mood disturbances are not simply linked to patients with obesity who have easy access to GLP-1 agonists. We know that obesity is associated with an increased risk for suicidal ideation and self-injury. There is another little-known observation: Weight loss is associated with a risk for suicide. It has been spoken about in relation to bariatric surgery. We know that after bariatric surgery (bypass or sleeve gastrectomy) the risk for suicidal ideation is double that of the preoperative period in the same population. And this risk is multiplied by close to four when comparing the population with a control group. But be careful because these data come from observational studies. Although the analysis I'm referring to when I'm speaking in relation to a control population is a control group, it isn't from a randomized trial. There is another interesting piece of data, which is that weight loss, regardless of the method used, is associated with an increased risk for suicide. This is what I found in two prospective studies involving this association, and there is no obvious explanation for it at this stage. Of course, there are lots of types of methodologic bias possible, but this poses the question of why there is a greater risk for suicide and self-injury in people taking a certain treatment and losing weight. In Practice Should we change our attitude towards prescribing GLP-1 agonists? For the moment, there are no recommendations in this regard. I don't think that it's reasonable to upend everything. Of course, the important thing is to adhere strictly to the treatment indications, and in a few weeks' time, we'll see the results from the analyses conducted by the French Health Authorities regarding the causal link between suicide risk and taking a GLP-1 agonist. With our current knowledge, I think we can all agree that losing weight is never a walk in the park. It's a change, for which individual physical and psychological consequences must be measured. Related Topic: Study Supports Efficacy of 9-Item Depression Screening in Identifying Patients at Risk for Suicide

Esketamine Bests Quetiapine for Severe Depression in Head-to-Head Trial BARCELONA — Intranasal esketamine (Spravato, Janssen) is superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression (TRD), results of a large, multicenter, head-to-head phase 3 trial show. Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission in comparison with quetiapine. More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates. The findings were presented here at the 36th European College of Neuropsychopharmacology (ECNP) Congress and were published online October 5 in The New England Journal of Medicine. New Hope The results provide "some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer," said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP. "These patients are not resistant, they just have resistance to monoaminergic drugs," he added. Esketamine, he said, is a "new weapon in our armamentarium." Reif said TRD is a serious condition that affects approximately 20% to 30% of those with major depressive disorder and has "substantial impact" on patients' lives, including quality of life and level of functioning. "We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment," Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was "urgently needed." For the trial, patients from 171 sites in 24 countries with TRD, defined as a <25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy. Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery–Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32. Reif said the study population was representative of a typical TRD population. The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30. Key Findings Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8 compared to those treated with quetiapine (27.1% vs 17.6%; P = .003). This equated to an adjusted odds ratio (OR) for remission of 1.74 (P = .003). Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% versus 14.1% with quetiapine; OR, 1.72 (P = .008). At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, vs 37.0% (P < .001). Reif noted that the definition of remission used in the study was a MADRS score of ≤10, but if the "more lenient" definition of ≤12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, vs 46.7%. Reif also presented results on functional remission rates beyond 32 weeks ― data that were not included in the study as published in NEJM. While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs 25.0%; OR, 1.88; P < .001). The safety data revealed no new signals, Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs 11.0% with quetiapine. Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it "greatly improves patients' functional impairment" while achieving "generally lower" adverse event rates. He added that they are currently running a significant number of secondary analyses "to give us a better grasp of which patient benefits most" from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection. "Tremendous Advance" Session co-chair Mark Weiser, MD, chairman at the Department of Psychiatry, Sackler School of Medicine, Tel Aviv University, Israel, told Medscape Medical News the results are "very exciting" and offer "further proof of a tremendous advance in our field." Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key. "It's great to improve symptoms," he said, "but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that's of extreme importance and makes us feel very optimistic about the future." Also commenting, Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, Barcelona, Spain, welcomed the findings. "The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine," he said in a release. "This gives people with treatment-resistant depression more safe treatment options." The study was funded by Janssen EMEA. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry. 36th European College of Neuropsychopharmacology (ECNP) Congress: Abstract S06.04. Presented October 8, 2023.

Editor's note: Find the latest long COVID news and guidance in Medscape's Long COVID Resource Center. As many as 2 out of 3 people with long COVID also have mental health challenges, including high rates of depression and anxiety, new research shows. It's a surprising finding that shows that those with long COVID may experience more mental distress than people with other chronic illnesses, such as Alzheimer's disease, cancer, diabetes, and cardiovascular disease. The study, published in The Lancet, followed 236,379 patients with long COVID. The investigators found that 62% of patients had received either a neurologic or a psychological diagnosis 6 months after being diagnosed with acute COVID. Mental distress associated with long COVID is a complex phenomenon that has biological, psychological, and social components, said Anna Dickerman, MD, a psychiatrist with New York–Presbyterian Hospital/Weill Cornell Medicine and associate professor of clinical psychiatry at Weill Cornell Medical College. This means that biological underpinnings caused by long COVID affect brain chemistry and give rise to psychological changes, putting a patient at higher risk for depression and anxiety, she said. In turn, changes in mental health can affect a person's risk of social effects such as job loss, disability, and isolation, which can affect self-esteem and self-worth, compounding anxiety and depression. Among patients with long COVID, all of these factors come together to cause what Dickerman has called "a perfect storm" that often results in depression, anxiety, and in some cases, suicidal thoughts. Dickerman and her colleagues at New York–Presbyterian Hospital are working to understand the mental health effects of long COVID so that patients are better able to recover from both the physical and mental health effects of this chronic condition. In an interview, Dickerman explained the mental health implications for people with long COVID and for the doctors who treat them. Excerpts of the interview follow. How does long COVID cause changes in the brain that result in depression? Long COVID causes inflammation in the brain that can cause the release of cytokines (proteins that are secreted from certain cells in the immune system) that are known to cause...fatigue, low energy, and low motivation ― symptoms which are also associated with depression and anxiety. What's more, if a patient had a serious case of acute COVID which led them to go on a ventilator, that too can cause changes in the brain. This means they could have had problems with their oxygenation status, and oxygen deprivation can have both acute and long-term effects on the brain. People can become delirious, meaning they have disturbances in their cognitive function, like attention and awareness (deficits). Patients may also have received steroids for treatment, which have been shown to impact mood and cause depression and anxiety. It's difficult to parse out because problems with attention and memory can also be associated with depression. Teasing apart what's from depression and what's from long COVID is tricky, but we do know that there's something unique about long COVID that causes cognitive deficiencies and changes. How do other factors associated with long COVID, such as insomnia, pain, and fatigue, affect the onset of depression and anxiety? Insomnia itself can be a symptom of depression. It may also be a physical symptom of long COVID similar to pain or difficulty breathing. And if you're not sleeping well, you're going to feel worse both physically and mentally. We also know that pain can affect mood and mood can affect pain — it's a bio-directional relationship. For example, if you're in pain, you're going to feel bad, and if you're depressed, that can also make your pain experience worse. Additionally, if you're in pain, it causes a physical limitation that can keep you from work or seeing your friends and family. These can all impact your social life. Limitations at work can also cause financial stress, which has been shown to impact mental health. Basically, it's a snowball effect that can make you more depressed, and the more depressed you become, the less you're able to participate in the activities that bring you happiness. Are rates of suicide higher in those with long COVID? Multiple studies have shown increased rates of suicidal ideation (thoughts) in patients with long COVID — and it's likely correlated with the degree of physical symptom burden, especially pain. This is consistent with what the research shows us of other chronic illnesses. In terms of specifically quantifying rates of completed suicides in the long COVID population, we simply need more epidemiological data. For now, I would say it's important for providers and the general population to know that these patients may be at increased suicide risk and to screen accordingly. Who is most at risk for mental distress associated with long COVID? Certainly anyone who had a preexisting mental health history before they got long COVID would be at a higher risk. There also seems to be disproportionate effects in those who have stressors related to other social determinants of health, like discrimination, poverty, and healthcare access. As a result, Black and Hispanic minority groups would be at a disproportionate risk for bad outcomes related to long COVID. What are the most effective treatments for those who have mental health problems associated with long COVID? This work is ongoing, and in the coming years we're likely to see new interventions. But for now, what we have in our treatment arsenal is the same evidenced-based treatments for anxiety and depression that we have in patients who don't have long COVID. For example, if a patient meets the clinical criteria for a major depressive episode or an anxiety disorder and they have long COVID, treatment would involve things like antidepressants and cognitive-behavioral therapy. Experts may also recommend a grated, gradual increase in physical activity in some patients with long COVID–associated depression. As a result of the number of people who got COVID, is there now an epidemic of mental health problems associated with the condition? In general, we're in the midst of a mental health epidemic as a result of the pandemic and all the effects that it's had on society, whether or not people had COVID. We're definitely seeing higher rates of depression and anxiety than we did before the pandemic. It's a group of patients that need attention. We also need more research over the next few years so that we can figure out better targeted treatments for this patient population. But for now, we know that it's important to work in an interdisciplinary model where we have psychiatrists working in close collaboration with pulmonologists, general practitioners, and cardiologists to holistically address both the physical and mental issues and not treat them in isolation, because we know there's a relationship.

Adults with greater adverse childhood experiences (ACEs) have higher attention deficit hyperactivity disorder (ADHD) symptom reporting than those with fewer ACEs, according to study findings published in the Journal of Attention Disorders. Yet, higher ACEs did not contribute to other psychological symptoms or worse neurocognitive performances. Studies that examine the relationship between objective cognitive performance and ACEs (early life experiences that may influence mental health outcomes) report conflicting results, and few studies have explored the relationship between objective cognitive performance and ACEs among individuals with self-reported ADHD symptoms. Therefore, investigators sought to characterize ADHD symptom reporting, neurocognitive performance, and other psychological symptoms among adults who experienced ACEs. The investigators conducted a cross-sectional study that began with 144 consecutive adults referred to an urban university academic medical center for neurological evaluation. Following the exclusion of 29 participants (primarily for invalid ADHD symptom reporting), a total of 115 individuals were included for analyses. On average, participants were aged 28.42 years (SD, 6.46), completed 16.47 years of education (SD, 1.99), and 65% (n=75) were women. Participants completed the ACE Questionnaire in which they self-reported ACEs, including emotional, physical, and sexual abuse along with neglect, and witnessing violence. Individuals were split into two groups based on these scores: the high ACEs group scored 4 or greater and the low ACEs group scored 3 or less. Participants also completed the Beck Depression Inventory-Second Edition (BDI-II), Beck Anxiety Inventory (BAI), and the Perceived Stress Scale (PSS). These measures were self-reports of depressive symptoms, anxiety, and perceived stress, respectively. In addition, all individuals completed a battery of standardized neuropsychological tests. "[O]ur results and the growing body of literature demonstrating links between ADHD and ACEs highlight the need for clinicians to consider ACEs during ADHD diagnostic assessments and treatment planning." Compared with the low ACEs group, the high ACEs group had higher ADHD symptom reporting for childhood impulsive (F =14.65; P <.001) and inattentive (F =11.31; P <.001) symptoms, and also reported significantly greater ADHD childhood symptom severity (F =11.31; P <.001). Similar results were found for the assessments of current/adulthood symptoms, with the high ACEs group reporting significantly higher levels of impulsive (F =7.24; P <.001) and hyperactive (F =4.62; P <.05) symptoms, along with greater symptom severity (F =5.51; P <.05) than the lower ACEs group. However, despite these group differences in self-reported ADHD symptoms, psychological symptom reporting of depression, anxiety, and perceived stress did not differ between the high ACEs group and the low ACEs group. Further, neurocognitive functioning was similar across all tested domains between the groups. These results demonstrate that a heavier burden of ACEs resulted in higher ADHD symptom reporting, but did not impact other psychological symptoms or neurocognitive performance. The investigators concluded, “[O]ur results and the growing body of literature demonstrating links between ADHD and ACEs highlight the need for clinicians to consider ACEs during ADHD diagnostic assessments and treatment planning.” Study limitations include recall bias during childhood data reporting and the inability to investigate causative factors due to the cross-sectional study design. References: Alfonso D, Basurto K, Guilfoyle J, et al. The effect of adverse childhood experiences on ADHD symptom reporting, psychological symptoms, and cognitive performance among adult neuropsychological referrals. Related Topic: Paying Attention to ADHD Prescriptions in Your Community ADHD Underappreciated in Older Adults

The risk for depression following retirement is higher in individuals who retire later in life, according to study findings published in The American Journal of Geriatric Psychiatry. Women and individuals living in rural areas seem particularly impacted. Thus far, most studies exploring retirement age and depression have been primarily conducted in Northern European countries with social welfare systems that provide significant support for pensions and employment, contributing to better mental health after retirement. Taiwan (with low labor force participation rates, long working hours, stressful working conditions, and the fastest current rate of population aging globally) is trending toward delayed statutory retirement age and prolonged working life, and the impact this environment may have on later-in-life depression has not been thoroughly explored. Therefore, investigators in Taiwan aimed to determine if retirement is associated with depressive disorders and if retirement age is a mitigating factor. The investigators conducted a population-based study using Taiwan’s National Health Insurance (NHI) dataset from January 2000 to December 2019. The NHI program in Taiwan enrolls about 99% of the national population and the dataset includes 2 million citizens determined by randomized sampling. The investigators identified 84,224 individuals who were aged 50 years and older, employed at the baseline, and had records of retirement during the follow-up period. The International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes were used to track the incidence of depressive disorders in the 7 years before and after retirement. "Instead of implying a beneficial mental effect of retirement, our results highlight that retirement represents a major life change and a potential stressor for older adults." The investigators found that age of retirement was oldest among those who had depression incidence before retirement (n=5111; 6.1%) and youngest among those with depression incidence after retirement (n=5222; 6.2%). For the subsequent analyses, participants with diagnosed depressive disorders prior to retirement were excluded. The investigators found the highest incidence of depressive disorders among individuals who retired after 69 years of age (8.15 per 1000 person-years) and those who retired between 65 and 69 years of age (7.6 per 1000 person-years). This risk of developing a depressive disorder was higher among individuals retiring in the 65 to 69 age group compared with the 60 to 64 group (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.02-1.18). Furthermore, the risk for depression was higher among women (aHR, 1.56; 95% CI, 1.47-1.65; P <.001), people living in rural areas (aHR, 1.11; 95% CI, 1.02-1.20; P =.015), and individuals with a Charlson Comorbidity Index of 1 (aHR, 1.40; 95% CI, 1.27-1.54; P <.001) or 2 and greater (aHR, 1.40; 95% CI, 1.28-1.52; P <.001). These study results indicate that retiring at a later age carries a higher risk of developing depression. The investigators concluded, “Instead of implying a beneficial mental effect of retirement, our results highlight that retirement represents a major life change and a potential stressor for older adults.” Study limitations include the use of insurance identities as proxy for retirement information, a lack of some demographic features, and an inability to identify individuals who may have depression but were not seeking medical help. References: Yang HJ, Cheng Y, Yu TS, Cheng WJ. Association between retirement age and incidence of depressive disorders: a 19-year population-based study. Am J Geriatr Psychiatry. Published online September 16, 2023. doi:10.1016/j.jagp.2023.09.010

Ketamine TOPLINE: Ketamine was no more effective than placebo in reducing depressive symptoms in surgical patients with major depressive disorder (MDD), results of a new study, which contradict prior research, suggest. Although symptoms improved in both study groups, investigators say participants' expectations of an improvement from ketamine may be driving that result. METHODOLOGY: The randomized, placebo-controlled trial included 40 patients who had previously been diagnosed with MDD and who were scheduled for elective noncardiac, nonintracranial surgery. Participants completed pre- and post-surgery depression screenings with the Patient Health Questionnaire-8 (inclusion score was ≥ 12) and the Montgomery-Ǻsberg Depression Rating Scale (MADRS). Patients received an infusion of 0.5 mg/kg of saline (placebo group; n = 20) or ketamine (n = 20) during surgery, along with general anesthesia. At the end of a 14-day follow-up, patients were asked to guess whether they had received ketamine or placebo. TAKEAWAY: MADRS scores dropped by around half 1 day after treatment, indicating an improvement in depressive symptoms in both the group that received ketamine (mean decrease from 25 to 12.6 points) and the group that received placebo (mean decrease from 30 to 15.3 points). There was no significant difference between the two. Participants in the ketamine and placebo groups also reported high rates of clinical response (60% and 50%, respectively) and remission (50% and 35%, respectively), again with no significant difference based on treatment with ketamine or placebo. Only 36.8% of participants accurately guessed their treatment group. Those who guessed they had received ketamine had higher MADRS scores than those who guessed they had received placebo or said they didn't know (10.1 vs 19.2 vs 23.0). The ketamine group had a significantly shorter hospital stay (1.9 days) than the placebo group (4 days) (P = .02). IN PRACTICE: "Our primary findings differ from those of previous antidepressant trials with ketamine conducted without adequate masking, which find robust effects of ketamine," the authors write, adding that "regardless of the intervention being tested, participant expectations of a positive outcome — also known as hope — may drive large decreases in depression symptoms seen in antidepressant trials." SOURCE: Heifets led the study, which was published online October 19 in Nature Mental Health. The study was funded by the Society for Neuroscience in Anesthesiology and Critical Care, the National Institutes of Health, and the Stanford School of Medicine Research Office. LIMITATIONS: The investigators did not measure participants' treatment expectations prior to randomization and could not determine what effect participant expectancy bias may have had on the results. In addition, there was no assessment of the blind for anesthesiologists who administered the ketamine or placebo to patients. DISCLOSURES: Heifets is on the scientific advisory boards of Osmind and Journey Clinical and is a consultant to Clairvoyant Therapeutics and Vine Ventures. Other disclosures are noted in the original article. Related Topic: Study Finds Esketamine Nasal Spray More Likely to Induce Remission in Treatment-Resistant MDD Than Quetiapine Extended Release FDA Approves First Oral Selective 5HT1A Receptor Agonist for MDD

The US Food and Drug Administration (FDA) has cleared the first over-the-counter test for the preliminary detection of fentanyl in urine. With the Alltest Fentanyl Urine Test Cassette (Hangzhou AllTest Biotech Co, Ltd), three drops of fresh urine are placed onto a cassette containing a fentanyl test strip. After 5 minutes, the test result appears as colored lines. "Opioid abuse, misuse and addiction is one of the most profound public health crises facing the US today. It is also a very personal issue for many people, impacting individual lives and families," Jeff Shuren, MD, JD, director, the FDA Center for Devices and Radiological Health, said in a statement. Shuren said this test is an example of the FDA's "continued commitment to authorize tools that can reduce deaths associated with overdoses. The agency expedited review of this test, making a decision on the submission in only 16 days from the date it was received." The FDA cautions that the urine test provides only a preliminary result and that a more specific, alternative chemical method (confirmation testing) must be used to confirm the result. The Alltest Fentanyl Urine Test Cassette includes a preaddressed mailing box for shipping samples to the manufacturer's laboratory for confirmation testing. The FDA also notes that the test may provide an incorrect result if the urine sample is contaminated, for example, by adding bleach. The test does not distinguish between drugs of abuse and certain medications. Consuming certain foods or food supplements can lead to a false positive test result. Related Topic: Fentanyl-Laced Stimulants Fuel Opioid Crisis' Fourth Wave

Recently I had the pleasure of speaking with Jonathan DePierro, Ph.D., about his newly updated book Resilience: The Science of Mastering Life's Greatest Challenges. DePierro is associate director of the Center for Stress, Resilience and Personal Growth (CSRPG) at New York's Mount Sinai Icahn School of Medicine. The book provides pragmatic practices based on years of clinical research with Vietnam veterans, 9/11 recovery workers, and others, backed up by inspiring stories of endurance and transformation. What Is Resilience, and How Can I Build It Up? Resilience can be hard to measure, and many longstanding ways to assess resilience, while helpful, have fallen short. For instance, resilience is not simply the absence of post-traumatic stress disorder; it is the presence of health and, often (but by no means exclusively), accompanied by post-traumatic growth. Regardless, resilience serves to buffer PTSD such that people with greater resilience are less likely to develop pathological outcomes following significant trauma. Not only that, but while many aspects of resilience are innate (related to biological factors affecting brain plasticity, for example), many resilience factors are learnable ("modifiable"). It is these modifiable factors people need to target, train, and track. DePierro and colleagues have developed the Mount Sinai Resilience Scale (2023), which enhances the capacity not only to assess resilience but whether its component factors are being applied effectively. At face value, its 24 items serve as an evidence-based framework for self-assessment as well as a means of identifying areas where resilience can be further trained. Increasing resilience correlates with enhanced long-term health outcomes and has been shown, at the organizational level, to be a cost-effective strategy. Investing in resilience now saves organizations significant costs in the future. Nevertheless, relatively few organizations actually implement robust and demonstrably effective resilience training into their key performance indicators and other measures of progress. Mount Sinai Resilience Scale Each item specifies a behavior or mindset likely to increase resilience and is rated on a scale from "Not at all true" (0) to "Almost always true" (4). For each item, the scale asks, "How useful/effective was this strategy?", highlighting the pivotal role of ongoing nonjudgmental self-appraisal. The scale can be used to track progress over time and identify areas where additional training is helpful. I confronted or faced my fears and problems directly. I actively tried to change or challenge negative or critical thoughts about myself or others. I attempted to become a positive example or role model of how to handle challenges. I turned to friends, mentors, family members, spiritual leaders, or teachers for advice on how to handle challenges. I made efforts to stay hopeful about the future. I sought the support of others. My choices and behaviors were consistent with my convictions of what is right and what is wrong. I told myself that the challenges in my life can lead to personal growth. When given the opportunity to choose my food, I chose foods that were nutritious or healthy. I did my best to get enough sleep. I participated in activities that gave me meaning and purpose. I took time to notice and understand my emotional and bodily reactions to stressful situations. I accepted that there are difficult emotions, situations, or people that I cannot change right now. I felt the positive impact of my religious and/or spiritual beliefs in many areas of my life. I took active steps to emotionally recover from stressful situations. I provided emotional, financial, or other types of support or donations to those in need. I offered support to others. I slowed myself down "in the moment" to handle intensely negative emotional reactions. I worked to forgive myself or others for doing something that was not in line with my values. I dedicated time to my hobbies or interests. I took the time to learn new skills or things that interest me. I made an effort to exercise. I held on to my sense of connection with a higher power or deity. I sought solace in spiritual practices such as prayer, meditation, or faith meetings. Conclusions There is certainly more to the story of satisfaction, wellness and health, recovery from trauma, illness and adversity than simply resilience. Resilience is, however, at the heart of the conversation and, while not a panacea, a foundational ingredient in a life well-lived, in hard times and all times. An updated manual of resilience, geared toward action-oriented steps as well as reflecting deep understanding, provides tools people can immediately deploy—tools sorely in need in today's increasingly stressful, crowded, and confusing reality. Over time, incorporating resilience strategies leads to a shift in one's overall approach to adversity and can be part of a plan for pursuing personal development. Small changes add up, but trying to do to all at once is the antithesis of resilience. It's wise to pick a couple of areas, work on small changes, see results, motivate persistence, and create a virtuous cycle. The goal, in a sense, is to cultivate a resilient personality. From sleep and exercise to cognitive flexibility, to finding meaning and/or faith, to being supported by others and supporting others, there are many relatively accessible, high-impact ways to begin to bend rigidity into resilience. Change that starts small and builds strength and flexibility over time also benefits from self-compassion, so that when we falter, we pick ourselves up with firm kindness rather than descend into self-criticism. Related Article: Growing from Adversity: How to Build Resilience

Child psychiatry primarily focuses on behavioral disorders and emotional problems that affect children, often characterized by anxiety reactions. Emotional maladjustment's in children may include habit disorders and conduct disorders. Parent-child relationships, school experiences, and perceptual difficulties can also contribute to personality problems. Child psychiatry is a branch of medicine that focuses on the study and treatment of mental, emotional, and behavioral disorders in children. It has been recognized as a subspecialty of psychiatry and neurology since the mid 1920s, with subdivisions including infant psychiatry and adolescent psychiatry. The approach to diagnosing and treating children's mental and emotional disturbances differs from that used with adults, as they are living through active and critical developmental phases. Child psychiatry primarily focuses on behavioral disorders and emotional problems that affect children, often characterized by anxiety reactions. Emotional maladjustments in children may include habit disorders and conduct disorders. Parent-child relationships, school experiences, and perceptual difficulties can also contribute to personality problems. Child psychiatry often involves family therapy and specialized methods like play therapy, which allows children to express their feelings, thoughts, wishes, and fears more freely and easily than through verbal communication. It would be much better to consult your Psychiatrist.

Are there potential problems in the latest study on antipsychotic medication reduction and discontinuation? Psychiatry A study on antipsychotic medication reduction and discontinuation came out yesterday with fanfare. The fanfare was basically because the principal investigator is a self-proclaimed critical psychiatrist with many criticisms of psychiatric medication and the results of her trial contradicted the primary hypothesis of the study and that was: “Our hypothesis was that antipsychotic reduction would improve social functioning with only a small increase in relapse rate.” Relapse rate in this case was defined as rehospitalization and the authors subsequently state that they thought a 10% rate of relapse would be “acceptable.” The irony of this situation (ideology versus real world treatment) was not lost on anyone. Several people seemed to congratulate the authors on publishing results inconsistent with their ideology although the study was so embedded in the UK research infrastructure – I doubt that not publishing it would have been an option. As a clinical trialist myself – the research seems to present several problems and creates several questions that could suggest that it was designed to optimize the likelihood that antipsychotic medication could be reduced and possibly discontinued. Before I get into those scenarios let me briefly summarize the results. The paper is open access and can be downloaded as well as another paper that describes the research protocol. In the study there were two arms an antipsychotic maintenance arm (N=127) and a reduction arm (N= 126). Diagnoses were taken from clinical information and the clinical staff had treatment responsibility for the patients. In those patients who were randomized to dose reduction, a tapering protocol was suggested to the clinical staff and if it went well at some point the option for a more rapid taper or discontinuation was offered. The research staff monitored the protocol. Baseline and outcome measure included a number of checklists to assess side effects, sexual side effects, positive and negative symptoms, quality of life, and social outcomes at the reassessment points. Raters were blinded but the measures are essentially self report. The ultimate result was that the risk of adverse outcomes was worse in the reduction arm with no associated improvement in social functioning. He are some potential issues that I noticed based on my experience in clinical trial design and on research review boards. 1. Recruitment – described in the following: “Participants were recruited from 19 National Health Service Trust mental health organisations across England. Potential participants were identified initially by clinical staff or recruited through advertisements placed in clinical settings and social media; those patients who expressed an interest in participating were sent further information”. Not enough information. What did the advertisements say? Were subjects aware of who was running this trial and what the goal of the research was? Were the patients asked why they were interested in participating in this trial? Were they asked what they think about taking a medication? Did the subjects have any exposure to the considerable press that the critical psychiatry group and the principal investigator generate? Descriptions in the lay press have been demonstrated to have significant effects on perceived side effects – even to the point of creating a nocebo effect (6) – is there any reason to think that a group emphasizing side effects and minimizing any therapeutic effects might have a similar impact? If that is the case – how would it affect this trial? 2. Inclusion/Exclusion criteria – “Exclusion criteria included being considered by a clinician to pose a serious risk of harm to self or others were the individual to reduce their antipsychotic medication, being mandated to take antipsychotic medication under a section of the Mental Health Act, having been admitted to hospital or treated by a crisis service for a mental disorder within the last month, lacking capacity to consent, having insufficient spoken English, pregnancy, breastfeeding, and being involved in another trial of an investigational medical product; eligibility was assessed by researchers and confirmed by the Principal Investigator for the site.” Practically all the exclusion criteria result in a population that may be more likely to discontinue antipsychotic medications with less difficulty. Consistent with this is the antipsychotic doses of both the reduction and maintenance arm of 300 mg chlorpromazine equivalents (on average). According to the Maudsley Prescribing Guidelines (4) 300 mg chlorpromazine is considered the minimally effective dose of medication for relapsing schizophrenia. Whether this was a representative sample of the 4109 patients put forward for research by clinicians a comparison of the demographics and medication doses would have been of interest. Selection bias may also be evident in the Consort diagram (page 4). After subjects consented to be contacted by the research team (N= 958) – a total of 562 declined participation. Was that because they did not want to take the chance of randomization to a medication reduction? 3. Diagnoses – the diagnosis required was schizophrenia or non-affective psychoses with recurrent episodes. The diagnoses were taken from clinical records. Considerable heterogeneity is introduced with the non-specific category of psychoses with an unpredictable course for which the concept of maintenance medication was not intended. 4. The Dose Reduction - The description of the dose reductions in the paper is confusing. It starts out describing individualized reductions every 2 months based on starting doses but at some point states the patient is allowed to discontinue the medication if the dose reduction has been going well or reduce at a rate of the equivalent of 2 mg haloperidol/day. 2 mg/day of haloperidol is not a slow reduction and it is a departure from reduction every 2 months. Some of the authors here have written about antipsychotic withdrawal reactions – how is the more rapid dose reduction or optional abrupt discontinuation justified? 4. Safety Monitoring/Informed Consent: The more clinical trials I read (and I have read thousands) – the more I want to see the consent form that each patient signs. Some of the authors here continuously talk about medication side effects. In fact – the principle investigator (PI) has stated that in her opinion that modern psychiatric medications work in a "drug centered" rather than a disease centered model by producing side effects like sedation, cognitive impairment, dysphoria, and loss of libido (5). In that model, symptoms of mental illness are muted by side effects rather than effectively treated. The model essentially denies the possibility of effective treatment without medication side effects. Of course, there are medication side effects but consent forms also must contain a discussion of the risks of the intervention. How are they listed when the investigators do not believe they can be directly addressed? Were the subjects told about the risk from medication discontinuation of recurrent psychosis, suicidal thinking, and death? That seems especially relevant in a study where the intervention arm had twice as many deaths as the maintenance arm . Along those same lines – the protocol paper for the study (2) states that a Data Safety and Monitoring Board (DSMB) assessed the ongoing safety of the protocol and made recommendation to a Programme Steering Committee providing independent oversight – even to the point of stopping the protocol if there was a substantial increase in adverse events related to the intervention. Was there a threshold? In this case why was that threshold not met? In the trials I have been involved with the PI and the physician responsible for monitoring safety (typically me) had to clearly delineate a safety plan if any of the research subjects developed medical or psychiatric complications from the intervention. In this case that responsibility seems to have been delegated to the clinicians originally treating the patient. In the reported causes of death of the trial participants – how is the death of a research subject in the reduction arm attributed to antipsychotic medication when they have been on a low dose, were being followed clinically in an outpatient clinic, and their dose was presumably being reduced? One patient in each arm died of an “accidental overdose”. What medication was implicated in the accidental overdoses? This protocol is also a case of shifting risk for the research to the clinicians. Here the research staff designs an intervention that likely will lead to worsening clinic status and the subjects are followed in a treatment as usual manner. Were any additional safeguards in place for that eventuality? For example – were the subjects informed that they could contact the principal investigator or research coordinator if things were not going well? These all seem like significant safety questions to me. 5. Social Functioning Scale (SFS) to measure the primary outcome - The measured results with this scale are in the top line of Table 2 at 6, 12, and 24 months. The scale has 79 items that are assigned to assess social functioning. Is there a problem with taking a cross sectional sample of people stabilized on medications and hypothesizing they will function better being tapered off antipsychotic medication? There is an obvious problem and that is there is no accounting for the improvement in social functioning due to the medication in the first place. In other words - what would the subjects have scored leading up to and during the episode of acute or recurrent psychosis - the reason they are taking the medication in the first place. What would the trajectory of these scores be over time? Stabilization of psychosis involves a lot more than treating hallucinations, delusions, and thought disorder symptoms. With stabilization there is an improvement in social behavior. The design of the trial suggests that the problem began with medications rather than a significant psychiatric disorder. There is a concept in clinical psychiatry and that is trying to get the patient as close as possible to their baseline level of functioning. That requires a knowledge of what they were like before the onset of illness and restoring as much functional and social capacity as possible. That also typically means minimal to no medication side effects if possible. 6. What is supported reduction of antipsychotic medication? Is there a protocol that I missed? I could not find what this means anywhere in either the protocol or final paper or in the supplementaries. If I was tapering an antipsychotic medication I would meet more frequently with the patient, inform them of what we need to watch for, have additional caregiver and family involvement, and encourage them to call me at specific signs of early problems due to the dosage reduction. In a research protocol, research staff would call and check on how the subject was doing. I would call all of that treatment as usual (TAU) when it comes to antipsychotic medication reduction. Is supported reduction more than that? Even TAU has been implicated as a potential placebo enhancing effect. Did it have that effect on the intervention in this case? 7. The overstated conclusion: “Our findings provide information for people with schizophrenia and related conditions about the probable medium-term impact of reducing the dose of their antipsychotic medication, and they highlight the need for collaborative decision-making based on the sharing and careful consideration of all the evidence.” Actually, it doesn’t. This is what clinical psychiatrists do and more specifically it is what I did for 35 years of practice. I can still recall community psychiatry seminars with Len Stein, talking about dosage reductions of antipsychotic medications and the implication of a WHO international study looking at that problem in schizophrenia. That seminar was in 1986. Collaborative decision making seems to be the latest term for informed consent and therapeutic alliance. Informed consent means that the patient is given enough information and discussion so that they can make a decision about the direction of their care including any medications, tests, or other interventions used. The therapeutic alliance is the affiliative relationship between the patient and physician aligned to address the patient's problems and diagnoses. It is by longstanding definition a collaboration. What the authors did encounter but did not discuss was the tendency of people on antipsychotics to just discontinue them (several in the maintenance group did this), how much withdrawal was encountered, and why there were no group categorical differences in side effects with the taper. According to the Glasgow Antipsychotic Side-effect Scale (GASS) guidelines all subjects remained in the moderate side effect range. And if medications work through side effects as the critical psychiatrists say why did the subjects in the dose reduction group worsen? Those are a few of the problems that jumped out at me as I read this paper and the associated backgrounder. As can be seen from the above discussion many of these design factors potentially optimize the intervention group in the direction of proving the authors’ hypothesis. It also limits generalizability to other clinical settings. That makes the result of the trial even more significant. It also raises some issues that seem more prominent in recent years as pharmaceutical conflict of interest seems to ring hollow. Is there an ideological conflict of interest and how is it determined? How does it affect research design, results, and the discussion of research findings? The Recent Takedowns of Adult ADHD Psychiatry seems doomed to argue endlessly about whether certain conditions exist or not and whether they can be characterized by written criteria. The latter condition is the most easily dismissed since clinical training is necessary to recognize conditions. You cannot just sit in an office, read the DSM and call yourself a psychiatrist. Whether conditions exist or not is more debatable but often slides into rhetoric that suggests inadequate training, ignorance, and/or significant conflict of influence or undue influence by the pharmaceutical industry. Consideration of the undue influence can easily be applied at the global level since Pharma has massive marketing efforts, direct to consumer advertising in the US, and at least one major political party pulling for them. That brings me to the recent commentaries about adult ADHD (1, 2). The first reference (1) doubts that adult ADHD exists for the most part and sees the diagnosis primarily as the result of a marketing scheme by Eli Lilly for atomoxetine and ignoring affective temperaments and other states that may affect attention. Atomoxetine was invented as a norepinephrine reuptake inhibiting antidepressant and like other members of this class of drugs – it did not work for depression. Since it is not technically a stimulant it was tested for ADHD and found to be effective. It is unique relative to other ADHD medications and not surprisingly it was heavily marketed while on patent. The patent expired on May 2017. The years on the market patent protected were 2002-2017. The first references to the diagnosis of adult ADHD were noted in the 1980s. Reference 2 suggests that the diagnosis of ADHD in children in the US is around 2-3% with adult numbers half that based on the work of one author. Contrasting numbers of a lifetime prevalence in adults as 8.1% and surveys estimating current prevalence at 4.4% are described as “absurdly high” but qualified on methodology (surveys vs interviews). Some authors have the opinion that books published about adult ADHD like Ratey and Hollowell's Driven to Distraction were a major source of public interest in the diagnosis and instrumental in getting it into the public vernacular. Before I get started – let me say that the only stake I have in this argument is making sure that the complexity of the situation is adequately described. Practically all the pro/con arguments in psychiatry are gross oversimplifications and based on what I know about the literature – I had no reason to expect that this was any different. I am already on record on this blog describing how to diagnose and treat ADHD and not fall into the common problems of misdiagnosis, prescribing to people with substance use problems, or prescribing to people who view these medications as performance enhancers. I have successfully treated adult ADHD with both on and off label medications and can attest to the fact that it is a valid and treatable diagnosis. Let me start out by looking at the prevalence estimates. These figures are very popular in the press to indict diagnosticians in the United States compared with some European countries and sell more papers. The problem with prevalence estimate is that the range can vary significantly due to methodological differences in the surveys. That question was looked at (3) and the title of that paper asked if ADHD was “an American condition”. The authors reviewed 22 studies based on DSM-III criteria and 19 studies based on DSM-IV criteria. Twenty prevalence estimates were done on the US and 30 were done in other countries. They demonstrated that the range of prevalence across all studies was approximately the same and that ADHD was not just an American condition. Since then numerous prevalence studies have been done in other countries – more recently using DSM-5 criteria showing similar ranges. On the issue of adult ADHD, a recent review looked at the issue adult ADHD and symptomatic adult ADHD prevalence by the 6 WHO regions (4). Their overall goal was to determine the worldwide prevalence of adult ADHD. They looked at the issue of persistent or childhood onset ADHD and symptomatic adult ADHD with no evidence of childhood onset and estimated the prevalence of those two groups separately. The pooled prevalence of persistent adult ADHD was 4.6% and for symptomatic ADHD it was 8.83%. These authors also looked at prevalence by a list of demographic factors, diagnostic criteria, addition to geographic areas as well as the decreasing prevalence by age groups. This study raises the issue of whether ADHD can be acquired rather than be a childhood onset illness. The reality is that there are many paths to acquired attentional deficit that have been treated over the course of my 35 years in the field. The best examples are neurodegenerative diseases, strokes, and brain injuries. Neuropsychiatrists have written about treating the associated cognitive, mood, and motivational deficits with stimulants. But a more relevant question is whether mechanisms exist that can result in people with none of these acquired brain injuries. The answer comes from modern genetics. Polygenic risk scores (of all diseases) suggest that there are high risk individuals who show no evidence of an illness as adults. These examples of incomplete penetrance are usually explained as environmental factors, additional genetic dynamics such as aging or protective factors. I see no reason why these factors could not occur in an ADHD genotype after childhood. The other significant genetic factor is spontaneous mutation or as a recent commentator put it: “You don’t die with the genome you were born with.” Psychiatry has focused on familial studies for the past 50 years, but it is likely that significant numbers of most conditions occur as the result of spontaneous mutations rather than strictly hereditary transmission. That is borne out in clinical practice every day. The authors (1) make the argument that ADHD is not a “scientifically valid” diagnosis. They explain “these symptoms have not been shown to be the result of a scientifically valid disease (adult ADHD) and better explained by more classic and scientifically validated psychiatric conditions, namely diseases or abnormalities of mood, anxiety, or mood temperament.” Mood temperament is a stretch. It is rarely commented on in adult psychiatry and then in extreme cases. It is not contained in the DSM. Part of the reason is selection bias. Psychiatrists are seeing people who have failed multiple other treatments and I have referred to this as being the treatment provider of last resort. Another factor is that ADHD is a quantitative rather than qualitative disorder – that is the cognitive symptoms are at the extreme end of normalcy and it is difficult to draw a line to demarcate illness from normal in many cases. A comparable example from medicine is hypertension. The cutoff for what is considered hypertension has varied significantly over the decades (9, 10) and even now considers antihypertensive side effects as a qualifier for treatment. That means that for any 2 people with the same marginally elevated blood pressure only one might get consistently treated. At one point hypertension was considered by some physicians to be a necessary compensatory mechanism that should not be treated (10). On the issue of quantitative aspects of psychiatric disorders in general – dimensional approaches are often suggested as a solution and the question is whether they work any better than the impairment criteria used in the DSM. That is especially true in a clinical setting where a patient is presenting with a clear problem that they are asking for help with On the issue of validity, studies have been done demonstrating reliability and validity (8) on both the DSM criteria as well as various rating scales for adult ADHD that are consistent with the diagnosis. There have also been detailed discussions of how to approach the problem clinically (11). Those discussions include how to differentiate mood disorders from ADHD and how to approach the functional impairment criteria in the clinical interview. That brings me to the issue of temperaments mentioned in reference 1. Temperaments have been researched in various contexts in psychiatry over the past decades. Most psychiatrists of my generation first heard about them on child psychiatry rotations and the work of Stella and Chess. In adults, temperaments are more descriptions of hyperthymia, cyclothymia, and dysthymia and are generally considered in the differential diagnosis of subclinical mood disorders. The best example is hyperthymia and it has been referred to both as a temperament and a personality. Hyperthymic people are generally high energy, require less sleep, and are social, talkative, and outgoing. They may be very productive and have increased libido relative to their peers. In clinical interviews they may say that their friends think they are “bipolar” and need to be treated. But careful interviewing demonstrates that they lack the symptom severity and degree of impairment necessary for a diagnosis of bipolar disorder. Ideally the initial interview results in that formulation and the psychiatrist can advise the person about why treatment is not necessary. Reference 12 looks at the issue of temperaments in a retrospective controlled study of patients being treated with stimulants who were referred to a mood disorders clinic. The authors acknowledge the selection bias in their study design. I can not think of a better design to pick up misdiagnosed patients than this one. To cite one example – of the 87 amphetamine treated referrals only 50% had a past diagnosis of ADHD. The authors acknowledge that there is no standard way to determine affective temperaments and decide to use the TEMPS-A with a cutoff of 75% of the items. If you are able to find a copy of the TEMPS-A (it is not easy) – you will find a list of 50 true-false questions like “I’m usually in an upbeat or cheery mood.” The questions are reminiscent of the Minnesota Multiphasic Personality Inventory (MMPI) except there are far fewer questions. The scoring guide suggests that the TEMPS-A can discriminate between hyperthymic, cyclothymic, dysthymic, and irritable temperaments. It is validated in the usual ways. The relevant question is whether any diagnosis made with this checklist would deter you from treating a comorbid condition - like Adult ADHD? It is one thing to survey a misdiagnosed group with the TEMPS-A and consider the clinical implications, but another to consider the presenting problem possible ADHD and whether it should be treated. The arguments in reference 2 about overdiagnosis, the existence of adult ADHD, and the idea that ADHD can occur in adults without a childhood diagnosis can be challenged with the facts and references provided here. The fact that we are in the midst of a multigenerational drug epidemic in an increasingly intoxicant permissive society does not mean that a diagnosis, treatment, or problem does not exist. It does mean that all psychiatrists from the moment they enter practice must exercise extreme caution when prescribing substances that reinforce their own use. The most likely cause of overdiagnosis is not because adult ADHD does not exist, not because of drug promotion (most are generic including the non-stimulant alternatives), or because MDs are careless. There are basically two reasons. First – the difficulty of diagnosing quantitative conditions. Second – sociocultural factors that exist in the US. Performance enhancement is built on the myth that you can tune your brain (or any organ) with supplements, nutrients, or medications to become a superior human being. The reality is you can alter your conscious state to believe that – but in the case of stimulants it is unlikely. The only real performance enhancement occurs because you can stay awake longer to read more and there is some evidence that your belief system is altered so that you believe you are smarter (14). These are just two of the reinforcing properties of stimulants that can lead to accelerated use and addiction. That is my brief summary of the complexity of this situation. For more on my approach to adult ADHD. Heart Rate Variability I have been following heart rate variability (HRV) on my watch and three different apps for the past several years. HRV is defined as the slight variations between R waves in the standard ECG recording. I have included an example below, illustrating the R-R’ intervals (or RRI) and how they might vary over time. Since HRV became widely available as a measurement off a watch that is commonly worn by millions of people, the research on this measurement and the variable studied has increased significantly. For my purposes – HRV is thought to be an indicator of heart health and conditioning and possibly a marker of overtraining – but advice about that varies significantly. Some studies have shown that decreased HRV is associated with an increased risk of arrhythmias. My recent cardiac ablation and cardioversion seemed to present an ideal situation for further study. Before getting into those details the physiology of HRV needs to be considered. The dominant heart rhythm of a normal heart is determined by the sinoatrial (SA) node. This node contains a population of spontaneously depolarizing cells that determine the rhythm and rate of the heartbeat. In addition to the neurophysiology of that cell population several additional factors affect both the rate and HRV. Primary among them is autonomic innervation from both the sympathetic and parasympathetic systems and their effect at the SA node. Parasympathetic fibers from the vagus nerve modulate slower firing through the neurotransmitter acetylcholine (ACh). Sympathetic fibers increase the rate of firing through the neurotransmitter norepinephrine (NE). NE has a longer half-life than ACh, but vagal tone is thought to be the most significant determinant of HRV. That is in line with several clinical observations including lower baseline heart rates in conditioned athletes and higher heart rates in people with less conditioning or in stressful situations. What happened to my heart rate and HRV during the recent cardiac ablation for atrial fibrillation and subsequent cardioversion? To answer that question, I had to figure out how to get the data off my Apple Watch 5.0. The only approach I could find was to downloaded all of the collected Health App data as a CSV file and then plot it in Excel. There are some online sites that you can download the data to and then use the remote software for plotting, but I preferred to retain control over the data. If you decide to do that and have several years of data like I did – it takes a long time. It took about 5 hours in my case to download about 1G of data to a zip file. From there it is easy to open that file with Excel or other software and do the plots. A useful addition to the Health App would be able to download specific time intervals. I have done 2 plots so far based on average daily HRV and hourly HRV as shown below. The plots are interesting because it clearly shows an effect from the ablation, a 96-hour period of atrial fibrillation and atrial flutter, and the cardioversion. At the minimum the baseline HRV drops to a different baseline after the ablation. That is followed by a significant spike with the recurrence of afib/flutter. And then there is a return to the lower baseline after the electrical cardioversion. I rarely had any significant episodes over the course of a year and whenever I went back and reviewed HRV it was not significantly changed. Since all those episodes were typically less than 2 or 3 hours it may not have been long enough to see an HRV effect. Conversely spikes of 50-100 msec in the HRV recording were common and not associated with arrhythmias. In the case of the post ablation period the sustained rates were associated with spikes, but since atrial flutter is regular, the associated R-R’ intervals probably showed a more characteristic HRV. I would expect to see an increase in vagal tone and therefore HRV just related to the sustained high rates over 4 days. If increased vagal tone correlates with increased HRV that does not seem to be the case in these graphs. The graphs also seem to indicate to me that there may be a structural element to HRV – either in the anatomical configuration of the conducting cells, their altered physiology, or a combination. The main implication for me at this point is to cautiously restart my conditioning efforts and see what impact that has on the HRV baseline. A second question is whether my HRV will approach the pre-ablation baseline. Electrocardiograms (ECG) may provide some clues in that direction. I have listed them below for references. Significant changes occurred in the immediate post ablation ECG and the post cardioversion ECG. An additional thought is whether non linear analysis of the RR intervals would yield more information and easily interpretable graphics. I have used some of these attractor plots in the past and also applied them to single electrode analyses of normal controls and patients with Alzheimer's disease. In terms of ECG analysis - see figure 5 in reference 2. In terms of theory - these attractor diagrams also imply changes in biological complexity at either the structural or functional level. George Dawson, MD, DFAPA ECG time course (1 -> 5 are in sequence): 1. Baseline - preop ECG 2. Post ablation ECG (following day): 3. Post ablation ECG - note anterior T wave changes thought to be consistent with procedure. 4. Precardioversion ECG showing atrial flutter at a high rate (day 5 of this arrhythmia; post op day 14). 5. Post cardioversion ECG showing NSR but flipped T waves in V1-V3. 6. ECG follow up 2 weeks after cardioversion showing T wave normalization in anterior leads. Heart Rate Variability Some recent recovery in HRV after a long period of low numbers in the 7-37 msec range following ablation and cardioversion.

Primum non nocere: above all, do no harm! KEY POINTS Autonomy, non-maleficence, beneficence, and justice are ethical principles that guide mental health care. Having an intentional process of ethical deliberation is essential. Clinicians need to act in the best interests of the people, families, and communities they serve. Ethical principles are especially pertinent to the conduct of professionals in psychology and psychiatry. The hard work comes when principles are in conflict, and clinicians must consider what values, biases, and obligations matter most. In the field of biomedical ethics, Tom Beauchamp and James Childress have had a seminal role in articulating fundamental ethical principles that guide professional conduct in a vast range of related specializations such as medicine, psychology, social work, and other health or social care services. Their book, Principles of Biomedical Ethics, has served as a practical guide for the development of many codes of ethics prepared by professional associations and regulatory bodies that oversee psychotherapy in various parts of the world. These four principles stand out: Autonomy: A person’s right to act as a free agent and the need to respect the rights of others to make free choices (respect for the client’s autonomy, dignity, and right to self-determination). Non-maleficence: “Above all, do no harm” (Latin: primum non nocere), i.e., not engaging in intentional physical or emotional harm or in actions with a high risk of harm. Beneficence: Engage in actions that benefit others and promote the welfare of the person who is suffering (including the prevention and the mitigation of harm). This means directing treatment in a way that promotes the best interests of the person you are working with; be careful not to project your perception of what is ‘best’ onto others. Justice: Treat people in similar circumstances similarly, and acknowledge when a person's circumstances differ and may require additional support. Justice means upholding the dignity and honoring the rights of all people. Practicing equity, inclusion, and attempting to address systematic inequalities are central components of justice. Ethical principles Other Ethical Principles to Consider: Trust: All relationships are built upon the foundation of trust. Being truthful, loyal, honest, and honouring one's commitments can create better outcomes for the individuals and communities we hope to support. Care: Always consider the unique interpersonal factors at play in a situation and act from a place of care, kindness, and responsibility—mental health providers should be attuned to others' needs. Transparency: sharing information and creating accessibility to knowledge in an honest, clear, and straightforward way at a level the person or family can understand is important. Societal interest: Upholding personal responsibility to always act in the best interests of society. This list of principles is not exhaustive, and many other ethical principles may be applicable to the context of different situations. However, the application of principles can sometimes come into conflict when making decisions, which is where the process of ethical deliberation truly begins. Ethical Deliberation If, after an evaluation of existing laws and guidelines, there is still no clear decision, further deliberation is required to explore values, personal biases, goals, and intentions to inform how we should make decisions. A deliberative ethical process requires us to understand the perspectives of the appropriate stakeholders and consider relevant values. Some values may feel right, but may not apply to the context of the situation. Once this information has been gathered, there are likely a couple of reasonable options on the table. To decide what option is the “best,” clinicians can deeply reflect on each available pathway forward. Practically, this may look like analyzing which action aligns best with the relevant values and principles previously identified. Some clinicians attempt to develop rational arguments for each ethical position in a given situation and attempt to choose the most logically defensible position. It is imperative for mental health care providers to also listen to their intuition and "gut feelings"—these will often elicit emotions that help us identify when an ethical conflict is being experienced. In learning to listen to your gut feelings or identifying an "ick factor," clinicians can create an intentional space to reflect on the context of the situation and unpack why such feelings are arising. This intuitive response can allow clinicians to practice critical reflectivity, identify how values may be at play or in conflict in client scenarios, and how different decisions within treatment may have risks or benefits that warrant substantial considerations. A suffering person’s well-being demands that mental health care providers act not on their own emotions, but rather deliberately focus on the best interests of the individuals, families, or communities they serve. This also means that professionals need to consider the interpersonal and cultural contexts in which people find themselves. After all, none of us exist in a social, cultural, or political vacuum. There are many processes of reflection and ethical frameworks that can help mental health professionals act with integrity, intentionality, and logic. Such reflection takes time and energy, but it is a choice clinicians get to make to ensure that our professions are held to the highest standard and that persons who are suffering receive the best care possible.