Hero

Videos

Slideshows

Articles

Podcasts

Poll

 covered a wide variety of psychiatric issues and industry updates, from the cross-cultural dimensions of psychosis to the economic burden of schizophrenia. Here are some highlights from the week.

HIPAA vs Ethical Care: Accounting for Privacy With Neuropsychiatric Impairments

The law presumes that individuals are rational. The reasonable individual, a hypothetical figure whose actions judges and juries weigh against others, will lucidly consider risks versus benefits before acting. Yet, we know that neuropsychiatric impairment can impede the capacity for making these calculated judgments, and in some cases this impairment is associated with a lack of illness awareness (or “insight”) that affects adherence with treatment.

Nevertheless, patients, families, and clinicians must still make critical health care decisions, such as a patient’s determination to engage in or refuse treatment, often with urgency and limited information. The COVID-19 pandemic has compounded the obstacles physicians commonly face in gaining patient acceptance of treatment and psychiatric referral; physicians often encounter exacerbated suspicion, mistrust, and emotional isolation even in individuals who do not suffer from neuropsychiatric impairment. 

Study Identifies Promising Potential Treatment for Alzheimer Disease

A study found that intranasal (IN) delivery of an oxytocin derivative to the brain may be an effective treatment for cognitive disorders such as Alzheimer disease.

Leveraging previous research suggesting that introducing cell-penetrating peptides (CPPs) and a penetration-accelerating sequence (PAS) via structural modifications can benefit the nose-to-brain delivery pathway, the investigators created the oxytocin derivative PAS-CPPs-oxytocin. Their goal was to see if IN delivery of this oxytocin derivative would help improve cognitive function in mice similarly to the more invasive intracerebroventricular (ICV) administration method. 

Schizophrenia is a chronic, severe, disabling mental health disorder that is associated with significantly increased morbidity and premature mortality. Schizophrenia is also associated with a significant economic burden. In the early 2000s, the annual cost of schizophrenia in the US was estimated to be greater than those for all cancers combined. These costs include direct health (eg, outpatient, inpatient, emergency department, and pharmacy) and non-health care (eg, law enforcement and homeless shelters), and indirect (eg, unemployment and premature mortality) costs. A more recent study estimated the annual US societal cost of schizophrenia in 2013 as about $156 billion. However, this estimated does not reflect recent health care system reforms and treatment advances. 

The Cross-Cultural Dimensions of Psychosis

Psychiatrists have been interested in the cross-cultural dimensions of psychosis since Emil Kraepelin (1856-1926) sailed to Java in 1904 and published his pivotal Vergleichende Psychiatrie (Comparative Psychiatry). Kraepelin provided the first known comparison of psychotic symptoms across populations: “The early stages of a depression were rarely seen, and violent excitement was also uncommon, but at the same time the very severe forms of dementia, so common in our own mental hospitals and found among the Europeans in Java as well, seem rarely to develop among the indigenous population.” 

. And be sure to stay up-to-date by subscribing to the 

Do you have a comment on any of these or other articles? Have a good idea for an article and want to write? Interested in sharing your perspectives? Write to us at 

From the cross-cultural dimensions of psychosis to the economic burden of schizophrenia, here are highlights from the week in Psychiatric Times.

The Week in Review: November 7-11

Leveraging previous research suggesting that introducing cell-penetrating peptides (CPPs) and a penetration-accelerating sequence (PAS) via structural modifications can benefit the nose-to-brain delivery pathway, the investigators created the oxytocin derivative PAS-CPPs-oxytocin. Their goal was to see if IN delivery of this oxytocin derivative would help improve cognitive function in mice similarly to the more invasive intracerebroventricular (ICV) administration method.

“We have previously shown that oxytocin reverses amyloid 𝛽 peptide (25-35) (A𝛽

)-induced impairment of synaptic plasticity in rodents,” said corresponding author Jun-Ichiro Oka, PhD, in a press release. “We wanted to see if PAS-CPPs-oxytocin could be delivered more efficiently to the mouse brain for clinical application, and if it improved cognitive functional behavior in mice.”

The investigators conducted Y-maze and Morris water maze (MWM) tests and found that ICV delivery of oxytocin showed memory-improving effects on the Aβ

-induced amnesia in both the Y-maze and MWM tests, while IN administration of the oxytocin derivative showed memory-improving effects in the Y-maze test. The investigators also found evidence that, following its IN administration, the fluorescein isothiocyanate-labeled oxytocin derivative was distributed throughout the brain.

“My team is the first to show that the oxytocin derivative can improve the A𝛽

-induced memory impairment in mice,” Oka said in a press release. “This suggests that oxytocin may help reduce the cognitive decline we see in Alzheimer’s disease.”

Oka, who is on the faculty of pharmaceutical sciences at Tokyo University of Science, further clarified that these findings are clinically useful because “the oxytocin derivative enters the brain more efficiently. Furthermore, since IN delivery is a non-invasive procedure, this modified version of the hormone could potentially be a clinically viable treatment for Alzheimer’s disease.”

1. Takahashi J, Ueta Y, Yamada D, et al. 

Intracerebroventricular administration of oxytocin and intranasal administration of the oxytocin derivative improve β-amyloid peptide (25-23)-induced memory impairment in mice

2. Novel derivative of “love hormone” oxytocin improves cognition impairment in Alzheimer’s. Toyko University of Science. News release. October 24, 2022. Accessed November 4, 2022. 

https://www.tus.ac.jp/en/mediarelations/archive/20221021_1000.html

Results show comparisons between intranasal and intracerebroventricular distribution of an oxytocin derivative.

 covered a wide variety of psychiatric issues and industry updates, from the relationship between psychotic disorders and dementia risk to major differences between bipolar I and bipolar II. Here are some highlights from the week.

Psychotic Disorders May Nearly Triple Dementia Risk

According to new research, individuals with nonaffective psychotic disorders are 2.5 times more likely than those without a nonaffective psychotic disorder to eventually develop dementia, representing a new avenue of modifiable risk.

In the first high-quality systematic review looking at a range of psychotic disorders and their association with dementia risk, researchers pulled together evidence from close to 13 million participants from 11 studies from 9 countries. The population of interest included adults at least 18 years old with a clinical diagnosis of nonaffective psychosis based on ICD criteria. Results indicated that psychotic disorders may have a stronger link with dementia than other mental health disorders like depression or anxiety. 

Lithium is associated with risk of chronic kidney disease (CKD), with an estimated prevalence of 10% to 35%. Fortunately, only a small proportion of chronic lithium users (perhaps 0.5% to 1%) develop CKD stage 4 or 5 (requiring hemodialysis or transplant). Data on the effects of discontinuing lithium on renal function are sparse and conflicting, and they are based on small samples. However, a Danish cohort study found that continuing lithium after a diagnosis of CKD was not associated with increased risk of developing end-stage CKD. Therefore, an understanding of the effects of lithium discontinuation on renal function would be important for clinical decision-making. 

Bipolar I vs Bipolar II: What are the Major Differences in Presentation and Treatment?

“Unfortunately, in the great majority of people, both bipolar I disorder and bipolar II disorder—especially bipolar II disorder—are not detected in a timely fashion.”

Roger S. McIntyre, MD, FRCPC, discussed the major differences between bipolar I and bipolar II disorder in a presentation at the 2022 Neuroscience Education Institute (NEI) Congress on November 3. The aim of the presentation was to identify the differences in the clinical presentation and diagnostic criteria associated with each disorder, and to determine the most effective pharmacologic treatments for each one. 

Youth, for the most part, are viewed collectively as a vulnerable group. Many young adults are referred to as “at-risk youth.” The term

 is difficult to define. According to the United Nations, youth is the period of transition from the dependence of childhood to the independence of adulthood. There is no consensus as to what age group represents that period. YouthPolicy.org defines 

 as those under 25 years of age and categorizes them into 3 stages: early adolescence (under 14 years), middle adolescence (15 to 17 years), and late adolescence and early adulthood (18 to 24 years). Individuals are, therefore, considered youth when they are between the ages of 14 and 25 years.

Youth do not live in a vacuum, and their issues should not be viewed, or addressed, in isolation of the bigger familial and societal contexts. Most human suffering happens due to ruptures in interpersonal relations, and most human healing takes place when ruptures are repaired through healing the relationships. This is not an easy task, but to change the current status quo of family dysfunction and human disconnection, it is important that youth be viewed as part of the solution—not only as part of the problem. 

From the relationship between psychotic disorders and dementia risk to the major differences between bipolar I and bipolar II, here are highlights from the week in Psychiatric Times.

The Week in Review: October 31-November 4

According to new research, individuals with nonaffective psychotic disorders are 2.5 times more likely than those without a nonaffective psychotic disorder to eventually develop 

, representing a new avenue of modifiable risk.

In the first high-quality systematic review looking at a range of psychotic disorders and their association with dementia risk, researchers pulled together evidence from close to 13 million participants from 11 studies from 9 countries. The population of interest included adults at least 18 years old with a clinical diagnosis of nonaffective psychosis based on ICD criteria. Results indicated that 

 may have a stronger link with dementia than other mental health disorders like depression or anxiety. Studies with typical and late-onset psychotic disorders, those with a higher percentage of women, those with a younger minimum age at baseline showed the strongest associations. As such, the study authors wrote, “Our narrative synthesis provided some evidence that people with psychotic disorders tended to be younger at dementia diagnosis and that the association between psychotic disorders and dementia was stronger when the interval between the two diagnoses was shorter.”

Despite speculations of the possible role of 

 in the development of dementia, the investigators only found 2 studies exploring this link. Moreover, those studies showed mixed results. One found a protective effect; the other found an increased risk associated with second generation antipsychotics but a protective effect for first generation antipsychotics.

“Cognitive impairment and hallucinations can be symptoms of both dementia and psychotic disorders, so it is possible there could be a link between the two illnesses. This impairment could also limit people’s cognitive reserve, and increase their vulnerability to dementia symptoms,” said lead author Sara El Miniawi of University College London.

Regardless of the age at which an individual first develops their mental illness, those with psychotic disorders are at a higher risk of dementia later in life. Additionally, individuals with a 

 tend to be younger than average at dementia diagnosis, as young as their 60s.

Previous research indicates that 4 in 10 dementia cases could be prevented or delayed by targeting risk factors from across the lifespan. This study’s findings add to the list of modifiable risk factors for dementia.

“People with psychotic disorders are more likely to have other health conditions such as cardiovascular disease or 

, which can increase the risk of dementia, while they are also more likely to have a poor diet, smoke or use drugs, which may harm their health in ways that could increase their likelihood of developing dementia,” said Vasiliki Orgeta, PhD, an associate professor at the Division of Psychiatry, Faculty of Brain Sciences at University College London.

The researchers were not able to determine whether effective treatment for psychotic disorders could mitigate the dementia risk, or whether antipsychotic medication could be a factor, as there was limited and conflicting evidence.

Non-affective psychotic disorders and risk of dementia: a systematic review and meta-analysis.

2. Schizophrenia may increase dementia risk by 2.5 times. UCL News. October 6, 2022. Accessed November 2, 2022. 

https://www.ucl.ac.uk/news/2022/oct/schizophrenia-may-increase-dementia-risk-25-times

Individuals with a psychotic disorder are 2.5 times more likely than those without one to develop dementia. 

Psychotic Disorders May Nearly Triple Dementia Risk 

According to a new study, treating depression could lower the risk of dementia for certain patients.

Using data collected by the UK Biobank, researchers examined more than 350,000 participants, including 46,280 participants with depression. During the study, 725 of the patients with depression also developed dementia. Participants were categorized into 1 of 4 courses of depression: increasing course, with mild initial symptoms that steadily increase; decreasing course, with moderate- or high-severity symptoms that decrease; chronically high course, with ongoing severe depressive symptoms; and chronically low course, with mild or moderate depressive symptoms that are consistently maintained.

“For subjects with late-life depression, it is crucial to receive timely treatment. The onset of dementia reduced most significantly among patients with an increasing course, while treatment turned out to be disappointing for those with persistent high symptoms. Thus, timely treatment might be essential for subjects [with depression],” study leader Jin-Tai Yu, MD, PhD, exclusively told 

The study results suggested that depression elevated the risk of dementia by 51% as compared with participants without depression. Participants with increasing, chronically high, or chronically low course depression were found to be more prone to dementia, while those with decreasing course faced no greater risk than participants without depression. Participants with depression who received treatment had a 30% reduced risk of dementia compared to untreated participants.

“This indicates that timely treatment of depression is needed among those with late-life depression,” said study lead Wei Cheng, PhD. “Providing depression treatment for those with late-life depression might not only remit affective symptoms but also postpone the onset of dementia.”

As to further research, the study leaders shared with Psychiatric Times that future studies are needed to unravel the effect of different treatment types.

“In our study, we did not find any comparable difference between treatment types. However, since only 725 participants developed dementia, after being stratified by specific treatment types and depression courses, the statistical power might be insufficient to yield significant conclusions,” said Dr Yu. “Therefore, future research should stratify subjects [with depression] by types of treatment, for example, cognitive behavioral therapy, interpersonal therapy, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, etc.”

Depression, depression treatments, and risk of incident dementia: a prospective cohort study of 354,313 participants.

2. Timely interventions for depression might lower the future risk of dementia. Elsevier. News release. October 17, 2022. Accessed November 2, 2022. 

https://www.biologicalpsychiatryjournal.com/pb/assets/raw/Health%20Advance/journals/bps/BPS_221017_PR_Yang_et_al_FINAL-1666034440127.pdf

According to new research, treating depression in older adults could decrease risk of dementia by 51%. 

Treating Depression to Prevent Dementia

 covered a wide variety of psychiatric issues and industry updates, from the psychiatric implications of the Parkland School mass shooting to what psychiatrists need to know about herbal medicine. Here are some highlights from the week.

App Intervention May Reduce Insomnia in Health Care Workers

Researchers studied an app-based Yoga of Immortals (YOI) intervention on the mental health of health care workers, including sleep disruption, and found that it produced a measurable benefit. There is a need to help health care workers with sleep trouble, as recent literature suggests that approximately 38% experienced insomnia during the COVID-19 pandemic.

“There is a compelling societal interest in developing interventions targeting the emotional needs of health care workers who are facing a public health crisis,” wrote Currie et al.

The YOI intervention teaches specific practices based on ancient yogic teachings and the 3 core components of the YOI program—breathwork, whole body movements, and postures—have multiple emotional benefits. 

On my most recent flight home (I know, I usually end up writing a new article every time I fly), I sat next to a middle-aged woman and her father who seems to be struggling with some kind of cognitive impairment, possibly dementia. I was very impressed with how, throughout our 2.5-hour long flight, that she was quite attentive to his every need and kept him both engaged and entertained. She did that through asking questions and sharing pictures saved on her phone that seemed to fill his soul with joy. 

The Parkland School Mass Shooting and Its Psychiatric Implications

Coincidentally, around the same time as the Sandy Hook School shooting trial of Alex Jones ended, a trial about the Parkland School mass shooting ended. We discussed some of the psychological implications of the former in Friday’s column, “The Psychological Heroism of the Sandy Hook Families.” Today we will primarily cover Parkland, with an added overall perspective on mental dysfunction and crime.

In the Parkland School trial, the major mental health issue seemed to be whether whatever mental health problems the shooter had should influence whether or not he got the death penalty. He did not. 

Herbal Medicine: What Psychiatrists Need to Know

Herbal medicines have been used to treat mental health disorders since ancient times. Many of the medications used in contemporary medicine originated from plants—salicylic acid from the willow tree, for example, and morphine from poppies. Numerous botanical treatments are useful in general psychiatry. This article discusses the most beneficial and commonly used herbal medicines to treat mental health concerns.

Americans spent $11.3 billion on herbal supplements in 2020, which represented a record increase in spending of 17.3% from 2019 to 2020. According to the 2020 COVID-19 consumer survey of the Council for Responsible Nutrition, among those who increased supplement intake, nearly a quarter cited mental health–related reasons, including stress and anxiety. 

From herbal medicine for psychiatrists to the psychiatric implications of the Parkland School massing shooting, here are highlights from the week in Psychiatric Times.

The Week in Review: October 17-21

On my most recent flight home (I know, I usually end up writing a new article every time I fly), I sat next to a middle-aged woman and her father who seems to be struggling with some kind of cognitive impairment, possibly 

. I was very impressed with how, throughout our 2.5-hour long flight, that she was quite attentive to his every need and kept him both engaged and entertained. She did that through asking questions and sharing pictures saved on her phone that seemed to fill his soul with joy.

Very few of us pay attention to our parents when they grow older, especially those with dementia. We seem to either take them for granted or get easily frustrated with them. Some of us even abandon them and then we wish for a different outcome when they are no longer with us.

I lost my mom in 2016. She was diagnosed with dementia during the ugly civil war in my home country, Libya. I do strongly believe that her memory quickly deteriorated because of the many times her heart broke losing loved ones to that nonsense. I was lucky to spend the last week of her life with her; I was holding her hand when she passed. She might have not remembered who I was, but I know deep in my heart that she felt I was there. I would have never had it any other way.

 before his death too. I remember him passing by my grandma’s room who died before him and him asking, “Where is the lady who used to be here?”

Maybe I am projecting my own fears about this ugly disease given that both my mom and her dad died of dementia-related complications. There is nothing I can do right now to change my genes or reduce my risk, but here are a few things I will do and encourage you to reflect on if one or both of your parent(s) is/are still alive:

1. Enjoy the current moment. Even if they do not have factual memories, create emotional memories for and with them, through moments of bonding, care, and tenderness.

2. Repair any damage in the relationship. Heal old wounds if there is room for healing. Forgive old ruptures if you can.

3. Focus on your spouse and children. Be emotionally available for them, so together you create long-lasting memories that they can cherish when they miss you.

4. Refuse the dysfunctional status quo. There is nothing normal about family breakdown.

5. Show respect, love, and compassion to the old people in your life and those around you. Not only your parents, but also your grandparents, uncles, aunts, older siblings and relatives, neighbors, and all seniors in your community. The global pandemic showed us how painful isolation is. The best cure for 

 is to build bridges and be a source of safety and solace for others.

6. And finally, do not forget to take care of yourself. Caregiving can bring joy, but can also lead to burnout if your neglect your own needs and boundaries.

Dementia is a mental health condition that can make or break families. Remember that behind the difficult behavior is your loved one—a human who deserves to be found, held, comforted, and tended to with the utmost love and compassion.

 is a practicing psychiatrist with Providence Healthcare System in Portland, Oregon. He is the author of 

The Wounded Healer: The Pain and Joy of Caregiving

A reminder to cherish your parents and the older adults in your life.

Dementia: A Social Death Sentence

The US Food and Drug Administration (FDA) sent a Complete Response Letter (CRL) regarding the supplemental new drug application (sNDA) for pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with Alzheimer disease psychosis (ADP), according to Acadia Pharmaceuticals.

The CRL indicated that the FDA has completed review of the application and could not approve the sNDA in its present form. The FDA recommended that Acadia conduct an additional trial in ADP.

“We are disappointed with this outcome. The treatment of Alzheimer disease psychosis continues to be an area of high unmet need, for which there is no approved therapy,” said Steve Davis, chief executive officer. “We want to express our gratitude to all of the patients, their families and investigators who have participated in our clinical trials.”

In Study 019, the FDA agreed the results demonstrated a statistically significant treatment effect on its primary endpoint, but the agency concluded there are limitations in the interpretability of said results. The FDA also stated that the positive treatment effect of pimavanserin on dementia-related psychosis in Study 045 (HARMONY) appeared to be driven by the robustly positive results in the Parkinson disease dementia subgroup, a condition they stated is subsumed within the currently approved Nuplazid Parkinson disease psychosis (PDP) indication.

This recent sNDA was Acadia's second attempt to secure approval for expanded use of the drug. In early 2021, the FDA rejected Acadia’s clinical trial data, which they stated were not sufficient to support approval of pimavanserin in patients with dementia-related psychosis.

1. Acadia Pharmaceuticals receives complete response letter from U.S. FDA for supplemental new drug application for pimavanserin for the treatment of hallucinations and delusions associated with Alzheimer’s disease psychosis. Business Wire. August 4, 2022. Accessed August 8, 2022. 

https://www.businesswire.com/news/home/20220804006095/en/Acadia-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-FDA-for-Supplemental-New-Drug-Application-for-Pimavanserin-for-the-Treatment-of-Hallucinations-and-Delusions-Associated-with-Alzheimer’s-Disease-Psychosis

2. U.S. FDA declines to approve expanded use of Acadia's antipsychotic drug. Reuters. August 5, 2022. Accessed August 8, 2022. 

https://www.reuters.com/business/future-of-health/us-fda-declines-approve-expanded-use-acadias-antipsychotic-drug-2022-08-05/

Alzheimer disease psychosis treatment pimavanserin receives Complete Response Letter from the FDA. 

Caution Ahead: FDA Asks for More Info on Expanded Use of Antipsychotic Drug

Brent Forester, MD, MSc, shares more about the neurocognitive epidemic of our time: dementia. As the baby boomer population ages, we are starting to see a rapid escalation of individuals with neurocognitive disorders both in America and worldwide. 

is the chief of the Division of Geriatric Psychiatry at McLean Hospital and medical director for Dementia Care and Behavioral & Mental Health Population Health Management at Mass General Brigham. He is also associate professor of psychiatry at Harvard Medical School. 

If we don't find a cure or adequate treatments, the number of individuals impacted by dementia could skyrocket to nearly 14 or 15 million Americans by 2050. 

Dementia: The Epidemic of Our Time

The first patient has been dosed in the TRANQUILITY II study of an acute treatment for agitation in patients with Alzheimer disease.

The TRANQUILITY II study, led by BioXcel Therapeutics, focuses on BXCL501, an orally dissolving thin film formulation of dexmedetomidine. In research incorporating multiple measurement scales, BXCL501 has demonstrated statistically significant reductions in agitation with no severe adverse events at doses of both 30 mcg and 60 mcg.

 The US Food and Drug Administration (FDA) granted BXCL501 breakthrough therapy designation for the acute treatment of agitation in connection with dementia in March 2021.

“We believe the recent FDA approval of BXCL501 for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults has laid a strong foundation for pursuing this Alzheimer’s-related agitation program to potentially address this debilitating symptom for patients,” Robert Risinger, MD, chief medical officer of BioXcel Therapeutics, said in a press release. “Importantly, we are also expanding TRANQUILITY II to more than 10 clinical trial sites in the US, and with no current FDA-approved treatments for agitation associated with this disease, we are making strong and swift efforts to potentially bring BXCL501 and its proven ability to address agitation to this large market.”

TRANQUILITY II is 1 of 2 studies—along with TRANQUILITY III—in BioXcel Therapeutics’ Phase 3 TRANQUILITY program, in which both studies measure the efficacy of BXCL501 in adults aged 65 years and older currently in assisted living facilities or nursing homes. BioXcel has reported that top-line data for TRANQUILITY II is expected in late 2022 or early 2023, and patient enrollment in TRANQUILITY III will begin later in 2022.

BioXcel Therapeutics announces first patient dosed in TRANQUILITY II phase 3 trial for acute treatment of agitation in patients with Alzheimer’s disease

. News release. GlobeNewswire. May 3, 2022. Accessed May 3, 2022.

BioXcel Therapeutics receives FDA Breakthrough Therapy Designation for BXCL501 for the acute treatment of agitation associated with dementia

. News release. BioSpace. March 15, 2021. Accessed May 3, 2022.

Top-line data for study is expected in late 2022, early 2023.

Dementia

The Week in Review: November 7-11

Study Identifies Promising Potential Treatment for Alzheimer Disease

The Week in Review: October 31-November 4

Psychotic Disorders May Nearly Triple Dementia Risk

Treating Depression to Prevent Dementia

The Week in Review: October 17-21

Dementia: A Social Death Sentence

Caution Ahead: FDA Asks for More Info on Expanded Use of Antipsychotic Drug

Dementia: The Epidemic of Our Time

Phase 3 Study on Treatment of Agitation in Alzheimer Disease Doses First Patient