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Tag: depression

  • Study shows antipsychotic drugs increase health risks in dementia patients

    Study shows antipsychotic drugs increase health risks in dementia patients

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    In a recent British Medical Journal study, researchers assess the adverse effects associated with the use of antipsychotic drugs in people with dementia.

    Study: Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. Image Credit: Fahroni / Shutterstock.com

    The role of antipsychotics in dementia management

    Individuals diagnosed with dementia undergo functional disability and progressive cognitive decline. Some common psychological and behavioral symptoms of dementia include anxiety, depression, apathy, aggression, delirium, irritability, and psychosis.

    To manage psychological and behavioral symptoms of dementia, patients are commonly treated with antipsychotics. The United Kingdom National Institute for Health and Care Excellence currently recommends the use of antipsychotics only when non-drug interventions are ineffective in alleviating behavioral and psychological symptoms of dementia. However, there has been an increase in antipsychotic use during the recent coronavirus disease 2019 (COVID-19) pandemic, which has been attributed to lockdown measures and the unavailability of non-pharmaceutical treatments.

    In the U.K., risperidone and haloperidol are the only antipsychotics that have received approval for the treatment of behavioral or psychological symptoms of dementia. In 2003, the United States Food and Drug Administration (FDA) highlighted the risks, such as stroke, transient ischaemic attack, and mortality, associated with the use of risperidone in older adults with dementia. 

    Based on multiple study reports, regulatory guidelines have been formulated in the U.K., U.S., and Europe to reduce inappropriate prescriptions of antipsychotic drugs for the treatment of behavioral and psychological symptoms of dementia. To date, few studies have provided evidence of the association between antipsychotic drug prescriptions in older adults with dementia and risks of multiple diseases, such as myocardial infarction, venous thromboembolism, ventricular arrhythmia, and acute kidney injury.

    About the study

    The current study investigated the risk of adverse outcomes associated with antipsychotics in a large cohort of adults with dementia. Some adverse outcomes considered in this study were venous thromboembolism, stroke, heart failure, ventricular arrhythmia, fracture, myocardial infarction, pneumonia, and acute kidney injury.

    Over 98% of the U.K. population is registered with National Health Service (NHS) primary care general practice. All relevant data were collected from the electronic health records held at the Clinical Practice Research Datalink (CPRD), which is associated with over 2,000 general practices. CPRD comprises the Aurum and GOLD databases, which can be considered as broadly representative of the U.K. population.

    Individuals above 50 years of age and diagnosed with dementia were recruited. Importantly, none of the study participants were under antipsychotic intervention one year before their diagnosis.

    The researchers utilized a matched cohort design, in which each patient who used antipsychotics after their initial dementia diagnosis was matched using the incidence density sampling method. This method considered up to 15 randomly selected patients who were diagnosed with dementia on the same date but were not prescribed antipsychotic drugs.

    Antipsychotics increase the risk of adverse effects in dementia patients

    Across the two cohorts, the mean age of the participants was 82.1 years. A total of 35,339 participants were prescribed an antipsychotic during the study period.

    The mean number of days between the first diagnosis of dementia and the date of a first antipsychotic prescription was 693.8 and 576.6 days for Aurum and GOLD, respectively. The most commonly prescribed antipsychotics were risperidone, haloperidol, olanzapine, and quetiapine.

    The current population-based study revealed that adults with dementia prescribed antipsychotics are at a greater risk of venous thromboembolism, myocardial infarction, stroke, heart failure, pneumonia, fracture, and acute kidney injury than non-users. This observation was based on analyzing 173,910 adults with dementia selected from both databases. 

    The increased risk of adverse outcomes was most prevalent among current and recent users of antipsychotic drugs. After 90 days of antipsychotic use, the risk of venous thromboembolism, pneumonia, acute kidney injury, and stroke was higher than non-users. However, antipsychotic drugs did not impact the risk of ventricular arrhythmia, appendicitis, and cholecystitis.

    As compared to the use of risperidone, haloperidol was significantly associated with an increased risk of pneumonia, fracture, and acute kidney injury. Although the adverse effects of haloperidol were higher than quetiapine, no significant differences were observed between risperidone and quetiapine for the risk of fracture, heart failure, and myocardial infarction. The risk of pneumonia, stroke, acute kidney injury, and venous thromboembolism was lower for quetiapine as compared to risperidone.

    Conclusions 

    The current study highlights how antipsychotic drugs affect older adults with dementia. The use of these drugs was associated with many serious adverse outcomes, such as stroke, acute kidney injury, pneumonia, venous thromboembolism, heart failure, and myocardial infarction.

    In the future, these risks must be considered, along with cerebrovascular events and mortality, while making regulatory decisions about the use of antipsychotic drugs for the treatment of dementia in older adults.

    Journal reference:

    • Mok, L. H. P., Carr, M. J., Guthrie, B., et al. (2024) Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ. doi:10.1136/bmj.2023.076268

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  • Global disease burden study highlights COVID-19 impact and health inequities

    Global disease burden study highlights COVID-19 impact and health inequities

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    Rates of early death and poor health caused by HIV/AIDS and diarrhea have been cut in half since 2010, and the rate of disease burden caused by injuries has dropped by a quarter in the same time period, after accounting for differences in age and population size across countries, based on a new study published in The Lancet. The study measures the burden of disease in years lost to early death and poor health. The findings indicate that total rates of global disease burden dropped by 14.2% between 2010 and 2019. However, the researchers found that the COVID-19 pandemic interrupted these downward trends: rates of disease burden increased overall since 2019 by 4.1% in 2020 and by 7.2% in 2021. This is the first study to measure premature death and disability due to the COVID-19 pandemic globally and compare it to other diseases and injuries. 

    The study reveals how healthy life expectancy, which is the number of years a person can expect to live in good health, rose from 61.3 years in 2010 to 62.2 years in 2021. Pinpointing the factors driving these trends, the researchers point to rapid improvements within the three different categories of disease burden: communicable, maternal, neonatal, and nutritional diseases; non-communicable diseases; and injuries. Among communicable, maternal, neonatal, and nutritional diseases, the burden of disease declined for neonatal disorders (diseases and injuries that appear uniquely in the first month of life), lower respiratory infections, diarrhea, malaria, tuberculosis, and HIV/AIDS between 2010 and 2021, ranging from reductions of 17.1% for neonatal disorders to 47.8% for HIV/AIDS. In the category of non-communicable diseases, disease burden from stroke dropped by 16.9%, while disease burden from ischemic heart disease fell by 12.0% during this period. 

    For injuries, the years of healthy life lost due to road injuries was slashed by nearly a quarter (22.9%), while disease burden from falls was reduced by 6.9%. Progress in reducing disease burden varied by countries’ Socio-demographic Index – a measure of income, fertility, and education – underscoring inequities. For example, the burden of disease due to stroke dropped by 9.6% from 2010 to 2021 in countries with the lowest Socio-demographic Index, but it declined faster – by 24.9% – among countries with higher Socio-demographic Index. 

    Our study illuminates both the world’s successes and failures. It demonstrates how the world made huge strides in expanding treatment for HIV/AIDS and combatting vaccine-preventable diseases and deaths among children under 5. At the same time, it shows how COVID-19 exacerbated inequities, causing the greatest disease burden in countries with the fewest resources, where health systems were strained and vaccines were difficult to secure. Governments should prioritize equitable pandemic preparedness planning and work to preserve the momentum that we’ve seen in improving children’s health.” 


    Dr. Alize Ferrari, Affiliate Associate Professor at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Honorary Associate Professor at the School of Public Health at the University of Queensland, and co-first author of the study

    The research presents updated estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The GBD 2021 study analyzes incidence, prevalence, years lived with disability (years lived in less-than-ideal health), and disability-adjusted life years (lost years of healthy life) at global, regional, national, and subnational levels. It presents estimates of health and health loss in age-adjusted rates and total rates per 100,000 people. The study provides globally comparable measures of healthy life expectancy and is the first study to fully evaluate burden of disease amid the first two years of the COVID-19 pandemic. COVID-19 was the single leading cause of disease burden worldwide in 2021, accounting for 7.4% of total disease burden globally. 

    The study also examined how the COVID-19 pandemic affected males and females differently. The researchers found that males were more likely than females to die of COVID-19; the age-standardized disease burden rate for COVID-19 among males was nearly twice that of females. However, the secondary effects of the COVID-19 pandemic, including long COVID and mental disorders, hit females hardest. For example, females were twice as likely as males to develop long COVID. Depression, which increased sharply during the pandemic, was most likely to affect females between ages 15 and 65. Looking at differences between age groups, COVID-19 caused the most disease burden in older adults. For COVID-19, adults 70 years and older had more than double the levels of disease burden compared to adults between the ages of 50 and 69. 

    The study highlights not only the diseases and injuries that cut life short and cause poor health, and how the burden of disease from different causes has changed over time, but also examines how these patterns differ across countries and regions. “In essence,” the authors write, the study “provides a comprehensive toolkit to inform and enhance decision-making processes across various levels of governance and practice.” 

    GBD 2021 shines a light on the different causes of disease burden, showing which ones have improved and which are stagnating or worsening. It also tallies the number of years that people are living healthy lives. Healthy life expectancy rose significantly in 59 countries and territories between 2010 and 2021, with the greatest improvements in countries ranking lowest on the Socio-demographic Index, jumping from 52.2 years in 2010 to 54.4 years in 2021. In contrast, healthy life expectancy showed minimal change among countries in the highest levels of the Socio-demographic Index, decreasing slightly from 68.9 years in 2010 to 68.5 years in 2021. The findings on healthy life expectancy demonstrate that even though people are living longer lives all over the world, they aren’t spending all those years in good health. The researchers found that the main causes of poor health were low back pain, depressive disorders, and headache disorders. 

    “With low back pain, the leading cause of poor health globally, we see that the existing treatments aren’t working well to address it,” said Dr. Damian Santomauro, Affiliate Assistant Professor of Health Metrics Sciences at IHME; Stream Lead at Queensland Centre for Mental Health Research; Adjunct Fellow at the School of Public Health at the University of Queensland; and co-first author of the study. “We need better tools to manage this major cause of global disease burden.” 

    “In contrast, for depressive disorders, we know what can work: therapy, medication, or both in combination for an adequate period of time. However, most people in the world have little or no access to treatment, unfortunately,” he said. “Considering how depression increased dramatically during the COVID-19 pandemic, it’s urgent to ensure that everyone with this disorder can get treatment.” 

    Another way to understand what is making people ill is by looking at which diseases are growing fastest. GBD 2021 reveals that diabetes experienced the most rapid growth among the different causes of poor health, what the researchers call years lived with disability. Age-adjusted years lived with disability due to diabetes rose by 25.9% between 2010 and 2021. Poor health from diabetes increased in every country and territory that the researchers studied. 

    “Diabetes is a major contributor to stroke and ischemic heart disease, which are among the top three causes of disease burden worldwide,” said Dr. Theo Vos, Professor Emeritus at IHME and one of the study’s senior authors. “Without intervention, more than 1.3 billion people in the world will be living with diabetes by 2050. To counter the threat of diabetes, we must ensure that people in all countries can access preventive care and treatment, including to anti-obesity medications, which can lower a person’s risk of developing diabetes.” 

    Source:

    Institute for Health Metrics and Evaluation

    Journal reference:

    GBD 2021 Diseases and Injuries Collaborators., (2024) Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. doi.org/10.1016/S0140-6736(24)00757-8.

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  • Is spousal cardiovascular disease associated with an increased risk for depression?

    Is spousal cardiovascular disease associated with an increased risk for depression?

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    Cardiovascular disease (CVD) is among the leading causes of illness and death in the current age. While CVD has long been linked to the onset of depression, not much is known about whether the spouses of those affected are more likely to become depressed after such events.

    A study recently published in JAMA Network Open explored this topic, laying the foundation for future prospective studies in this field.

    Study: Depression Onset After a Spouse’s Cardiovascular Event. Image Credit: Chay_Tee/Shutterstock.comStudy: Depression Onset After a Spouse’s Cardiovascular Event. Image Credit: Chay_Tee/Shutterstock.com

    Depression and health

    Depression has become 65% more prevalent, and it stands as the predominant mental health disorder worldwide, not only diminishing quality of life but also adversely affecting overall health.

    Depression is associated with a higher risk of CVD, dementia, poor cognition, and death.

    How is CVD linked to depression?

    CVD and depression are both more common in people who are obese, and both share inflammation in the immune system. When someone suffers a CVD event such as a stroke or a heart attack, the family also suffers from mental stress, anxiety, and even depression.

    The current study was designed to explore the association between CVD and depression at the household level. The data came from a national database maintained by the Japan Health Insurance Association (JHIA).

    This included about 40% of the Japanese working-age population or 30 million individuals in this age group.

    What did the study show?

    The researchers found that among nearly 278,000 married couples matched for important characteristics, the vast majority (95%) reported a CVD-related event in the male partner. The mean age of the patients was 58 years.

    Those whose spouses had a CVD event were more likely to be diabetic, hypertensive, or depressed compared to the other group. The spousal group had an increased cumulative incidence of depression, between 4% to 5% for males and females, respectively.

    For spouses between 20 and 59 years, about 4% of spouses became depressed vs 3% of those aged 60 years or more.

    New-onset depression was observed in nearly 2% of individuals. Spousal risk for depression after a CVD was 13% higher than in the group without such an event.

    This did not show any change by age, sex, income, or a previous CVD history.

    However, depression risk was higher by 13% to 15% after spousal stroke or heart failure, but not after a heart attack.

    Other potentially confounding factors included smoking, drinking, exercise, or whether the index patient was using drugs to reduce blood pressure. None of these showed any impact on the risk of depression in the spouse, however.

    The researchers also checked for the possible interaction of these results with the spouse’s health status.

    They examined the body mass index (BMI), blood pressure, cholesterol levels, blood sugar concentrations, and kidney function. They found that the same increased risk was manifested after controlling for these factors.

    The study corroborates the depressive effect of a spousal CVD event, which could involve a need to be a caregiver for the sick spouse.

    This could mean inevitable lifestyle alterations, lack of other social interactions, sleep disruptions, and lack of exercise. All these are associated with chronic mental stress, which increases with the level and duration of caregiving.

    Financial problems due to the forced loss of employment to manage the spouse’s needs, with additional caregiving-related costs, are another source of stress.

    Finally, grief at the loss of a spouse or distress related to the stay of the loved one in the intensive care unit may trigger depression.

    Conclusions

    “These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.”

    By paying attention to possible confounders such as a history of other diseases, individual practice of healthy habits, and physical health parameters, the study fills a knowledge gap and provides stronger evidence.

    Community-level and multidisciplinary clinical support systems should be studied as a possible intervention to reduce this risk for spouses of CVD patients through a wide-spectrum preventive care approach.

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  • Ketamine’s rapid impact on depression linked to immune system pathways

    Ketamine’s rapid impact on depression linked to immune system pathways

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    In a recent study published in Molecular Psychiatry, researchers review the anti-inflammatory effects of ketamine in the peripheral and central nervous systems. To this end, all relevant articles were obtained from PubMed and Web of Science databases, with both animal and human studies published until September 2023 considered for the analysis.

    Study: Ketamine’s mechanism of action with an emphasis on neuroimmune regulation: Can the complement system complement ketamine’s antidepressant effects? Image Credit: Jack_the_sparrow / Shutterstock.com

    Treating major depressive disorder

    Major depressive disorder (MDD) is a mood disorder associated with persistent feelings of loss of interest and sadness. Current estimates indicate that over 300 million individuals are affected by MDD globally, about 700,000 of whom commit suicide each year. Altered neurotrophin levels and monoamine dysregulation are both mechanisms that have been attributed to manifestations of MDD.

    Monoamines associated with noradrenergic, serotoninergic, and dopaminergic activities can be regulated through certain pharmaceutical agents to improve the cognition, sleep, and mood of MDD patients. However, conventional monoamine antidepressant therapy has only been shown to be effective in 30-40% of patients with MDD. 

    According to the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a significant number of MDD patients do not respond to standard treatment. Patients who fail to respond to two antidepressants of suitable dosage are known to suffer treatment-resistant depression (TRD). 

    Racemic (R, S)-ketamine, which is more commonly referred to as ketamine, and (S)-ketamine (esketamine) have shown significant positive effects on MDD. As compared to conventional treatments, ketamine has been shown to exert antidepressant effects within a few hours. Many TRD patients have also responded positively to a single ketamine infusion.

    Mechanism of action of ketamine for MDD treatment

    The mechanisms that underlie the antidepressant effects of ketamine are associated with the N-methyl-D-aspartate (NMDA) receptor, opioid pathway, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and mechanistic target of rapamycin (mTOR). 

    Various neuronal cells, including microglia and astrocytes, regulate neuroinflammation. Individuals with MDD often exhibit lower levels of glial fibrillary acidic protein (GFAP) and glutamate transporter-1 (GLT-1). In these patients, an acute administration of ketamine normalized these levels, thus improving their mood. 

    In vivo experimental findings have also shown that ketamine has an inhibitory effect in lipopolysaccharide (LPS)-induced microglial activation, which led to improvements in depressive-like behaviors. Rodent studies have also reported that transforming growth factor β (TGF)-β, an anti-inflammatory molecule inhibiting excessive microglial activation, is associated with the differential antidepressant effects of ketamine enantiomers.

    Mouse models have revealed that (R)-ketamine, and not (S)-ketamine, alleviates stress-induced reduction in the expression of Tgfb1 and its receptors Tgfbr1 and Tgfbr2. Nevertheless, additional research is needed to clarify the microglia-based mechanisms underlying the antidepressant effects of ketamine.

    Patients with MDD exhibit higher interleukin 6 (IL-6) and tumor necrosis factor ⍺ (TNF-⍺) levels than non-depressed individuals. One rodent study revealed ketamine administration normalized these levels and improved MDD symptoms.

    Higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) have been observed in patients with MDD. Administration of 0.5 mg/kg ketamine infusions for twelve days led to symptomatic improvement that was associated with significant downregulation of GM-CSF. 

    Ketamine and the immune response

    The antidepressant effects of ketamine have been linked with the complement system, which is a vital component of synaptic plasticity. The complement system comprises 30 proteins that are involved in the classical, alternate, and lectin pathways, all of which converge in C3 cleavage, a major complement component.

    Complement proteins play a crucial role in the regulation of cell proliferation, maturation, and responsiveness. Activation of the complement system results in the release of complement and immune molecules that are linked with inflammatory responses.

    Increased levels of serum complement components C3a and C5a have been observed in bipolar disorder. Similarly, a high concentration of serum C1q levels is found in patients with MDD.

    An in vivo experiment with C5a receptor knockout mice highlighted the neuroprotective role of C5a against glutamate excitotoxicity-induced apoptosis through elevated expression and regulation of glutamate receptor subunit 2 (GluR2). Glutamatergic modulation has been established as a mechanistic commonality between the complement system and ketamine. 

    Ketamine also activates mTORC1 by triggering the brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and NMDA receptors. Additionally, the the C3a ligand-C3a receptor in CD4 + T-cells leads to mTOR activatiwhich is on, essential for cell survival. Complement-mTOR activation also modulates many stress and metabolic pathways, such as cytokine secretion, oxidative phosphorylation, and inflammasome activation.

    Conclusions

    The current study indicated the potential association between the complement system and the antidepressant effects of ketamine. Nevertheless, additional studies are needed to improve treatment outcomes for MDD using ketamine.

    Journal reference:

    • Quintanilla, B., Zarate, C. A., and Pillai, A. (2024) Ketamine’s mechanism of action with an emphasis on neuroimmune regulation: Can the complement system complement ketamine’s antidepressant effects? Molecular Psychiatry; 1-10. doi:10.1038/s41380-024-02507-7

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  • Breakthrough brain stimulator could revolutionize treatment for neurological disorders

    Breakthrough brain stimulator could revolutionize treatment for neurological disorders

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    Rice University engineers have developed the smallest implantable brain stimulator demonstrated in a human patient. Thanks to pioneering magnetoelectric power transfer technology, the pea-sized device developed in the Rice lab of Jacob Robinson in collaboration with Motif Neurotech and clinicians Dr. Sameer Sheth and Dr. Sunil Sheth can be powered wirelessly via an external transmitter and used to stimulate the brain through the dura ⎯ the protective membrane attached to the bottom of the skull.

    The device, known as the Digitally programmable Over-brain Therapeutic (DOT), could revolutionize treatment for drug-resistant depression and other psychiatric or neurological disorders by providing a therapeutic alternative that offers greater patient autonomy and accessibility than current neurostimulation-based therapies and is less invasive than other brain-computer interfaces (BCIs).

    In this paper we show that our device, the size of a pea, can activate the motor cortex, which results in the patient moving their hand. In the future, we can place the implant above other parts of the brain, like the prefrontal cortex, where we expect to improve executive functioning in people with depression or other disorders.”


    Jacob Robinson, professor of electrical and computer engineering and of bioengineering, Rice University

    Existing implantable technologies for brain stimulation are powered by relatively large batteries that need to be placed under the skin elsewhere in the body and connected to the stimulating device via long wires. Such design limitations require more surgery and subject the individual to a greater burden of hardware implantation, risks of wire breakage or failure and the need for future battery replacement surgeries.

    “We eliminated the need for a battery by wirelessly powering the device using an external transmitter,” explained Joshua Woods, an electrical engineering graduate student in the Robinson lab and lead author on the study published in Science Advances. Amanda Singer, a former graduate student in Rice’s applied physics program who is now at Motif Neurotech, is also a lead author.

    The technology relies on a material that converts magnetic fields into electrical pulses. This conversion process is very efficient at small scales and has good misalignment tolerance, meaning it does not require complex or minute maneuvering to activate and control. The device has a width of 9 millimeters and can deliver 14.5 volts of stimulation.

    “Our implant gets all of its energy through this magnetoelectric effect,” said Robinson, who is founder and CEO of Motif, a startup working to bring the device to market. “The physics of that power transfer makes this much more efficient than any other wireless power transfer technologies under these conditions.”

    Motif is one of several neurotech companies that are probing the potential of BCIs to revolutionize treatments for neurological disorders.

    “Neurostimulation is key to enabling therapies in the mental health space where drug side effects and a lack of efficacy leave many people without adequate treatment options,” Robinson said.

    The researchers tested the device temporarily in a human patient, using it to stimulate the motor cortex ⎯ the part of the brain responsible for movement ⎯ and generating a hand movement response. They next showed the device interfaces with the brain stably for a 30-day duration in pigs.

    “This has not been done before because the quality and strength of the signal needed to stimulate the brain through the dura were previously impossible with wireless power transfer for implants this small,” Woods said.

    Robinson envisions the technology being used from the comfort of one’s home. A physician would prescribe the treatment and provide guidelines for using the device, but patients would retain complete control over how the treatment is administered.

    “Back home, the patient would put on their hat or wearable to power and communicate with the implant, push ‘go’ on their iPhone or their smartwatch and then the electrical stimulation from that implant would activate a neuronal network inside the brain,” Robinson said.

    Implantation would require a minimally invasive 30-minute procedure that would place the device in the bone over the brain. Both the implant and the incision would be virtually invisible, and the patient would go home the same day.

    “When you think about a pacemaker, it’s a very routine part of cardiac care,” said Sheth, professor and vice-chair of research, McNair Scholar and Cullen Foundation Endowed Chair of Neurosurgery at the Baylor College of Medicine. “In neurological and psychiatric disorders, the equivalent is deep brain stimulation (DBS), which sounds scary and invasive. DBS is actually quite a safe procedure, but it’s still brain surgery, and its perceived risk will place a very low ceiling on the number of people who are willing to accept it and may benefit from it. Here’s where technologies like this come in. A 30-minute minor procedure that is little more than skin surgery, done in an outpatient surgery center, is much more likely to be tolerated than DBS. So if we can show that it is about as effective as more invasive alternatives, this therapy will likely make a much larger impact on mental health.”

    For some conditions, epilepsy for example, the device may need to be on permanently or most of the time, but for disorders such as depression and OCD, a regimen of just a few minutes of stimulation per day could suffice to bring about the desired changes in the functioning of the targeted neuronal network.

    In terms of next steps, Robinson said that on the research side he is “really interested in the idea of creating networks of implants and creating implants that can stimulate and record, so that they can provide adaptive personalized therapies based on your own brain signatures.” From the therapeutic development standpoint, Motif Neurotech is in the process of seeking FDA approval for a long-term clinical trial in humans. Patients and caregivers can sign up on the Motif Neurotech website to learn when and where these trials will begin.

    The work was supported in part by The Robert and Janice McNair Foundation, the McNair Medical Institute, DARPA and the National Science Foundation.

    Source:

    Journal reference:

    Woods, J. E., et al. (2024) Miniature battery-free epidural cortical stimulators. Science Advances. doi.org/10.1126/sciadv.adn0858.

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  • Can psychedelics improve sexual functioning and satisfaction?

    Can psychedelics improve sexual functioning and satisfaction?

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    In a recent study published in the journal Scientific Reports, researchers explored the influence of psychedelics on sexual functioning using a large, naturalistic study and a controlled clinical trial that compared the impacts of psilocybin and selective serotonin reuptake inhibitors (SSRI) on various facets of sexual functioning in patients with major depressive disorders.

    Study: Psychedelics and sexual functioning: a mixed-methods study. Image Credit: Cannabis_Pic/Shutterstock.comStudy: Psychedelics and sexual functioning: a mixed-methods study. Image Credit: Cannabis_Pic/Shutterstock.com

    Background

    Research on psychedelic substances has followed a relatively unsteady trajectory, with various clinical studies through the 1950s and up to the 1970s examining the use of lysergic acid diethylamide (LSD) for treating alcohol dependence and mood disorders.

    Psychedelics also played a major role in the social movements of the 1960s, such as the anti-war protests and hippy culture. The 1971 Act on Controlled Substances passed by the United Nations, however, brought most of the scientific research on psychedelics to a halt.

    Recent studies indicate a revival of research interest in the use of psychedelics as therapeutic avenues for mental health disorders. Studies have examined the effectiveness of psilocybin therapy in alleviating symptoms of depression and anxiety.

    Psilocybin also showed comparable efficacy to the SSRI escitalopram in lowering symptoms of depression, with significantly better performance in secondary outcomes such as anhedonia, general functioning, and well-being.

    Given that sexual dysfunction is a common symptom in patients with major depressive disorder, and it is also the side effect of most SSRIs, it is essential to explore the impact of psychedelics on sexual function.

    About the study

    In the present study, the researchers examined the use of psychedelics in naturalistic settings and ceremonies to understand its effect on various aspects of sexual functioning.

    The association was further investigated in a six-week-long clinical trial comparing psilocybin with escitalopram. Sexual functioning was explored along the domains of sexual satisfaction, pleasure, arousal, body image, importance of sex, and sexual desires.

    The researchers also aimed to understand whether psychedelics influenced sexual openness and desires for sexual exploration using a set of self-constructed questions. Additionally, the study evaluated the differences in this association among male and female patients.

    Although not a core symptom, sexual dysfunction is very common in individuals with major depressive disorders, with the most frequently reported symptoms being difficulty getting aroused, lower libido, and a delay in or absence of orgasms in patients of both sexes.

    Furthermore, sexual dysfunction is also known to be a common side effect of SSRIs such as fluoxetine, citalopram, and escitalopram.

    Impairments in sexual function due to SSRIs are thought to be due to the downstream impact of SSRIs on dopaminergic and serotoninergic. Sexual dysfunction can also significantly lower self-esteem and impact the quality of relationships and life.

    Sexual satisfaction has also been linked to lower depression rates among individuals of both sexes.

    For the first part of the study, the researchers gathered data from individuals who attended a ceremony that involved the consumption of psychedelics such as magic mushrooms, psilocybin, ayahuasca, LSD, N, N-Dimethyltryptamine, etc.

    The second part of the study involved data obtained from a double-blinded, controlled, phase II clinical trial that compared the effectiveness of psilocybin therapy against that of escitalopram therapy against major depressive disorder.

    Results

    The results from the naturalistic study showed that the use of psychedelics brought about improvements in various domains of sexual satisfaction and functioning, including body image, partner satisfaction, and improvements in communication and pleasure during sex.

    The clinical trial included in the study also supported these findings and reported that the post-acute effects of psilocybin therapy with respect to sexual functioning were positive, while those of escitalopram therapy were not.

    The findings suggested that while both psilocybin and escitalopram therapy resulted in comparable reductions in the symptoms of depression, escitalopram had a significant negative impact on sexual functioning.

    However, the researchers also stated that these results on the negative impact of escitalopram must not be generalized to all SSRIs since various SSRIs have been developed that do not cause sexual dysfunction to the same extent as escitalopram.

    The difference in the impacts of escitalopram and psilocybin on sexual functioning could be linked to the different mechanisms by which they alleviate depression.

    SSRIs inhibit serotonin re-intake, increasing serotonin concentrations and promoting serotonin activity in the post-synaptic phase.

    This impacts the downstream serotoninergic and dopaminergic functioning, subsequently impacting acetylcholine, testosterone, and nitric oxide levels that affect libido.

    Conclusions

    Overall, the results showed that the use of psilocybin in treating major depressive disorder might have a positive impact on sexual functioning.

    While this association needs to be explored further through validated measures, the findings do support the fact that psychedelics not only reduce the symptoms of major depressive disorder but could also be potentially important treatment options for other disorders that have reduced sexual functioning.

    Journal reference:

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  • Esketamine after childbirth cuts risk of postnatal depression by three-quarters

    Esketamine after childbirth cuts risk of postnatal depression by three-quarters

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    In a recent study published in the British Medical Journal, researchers investigated whether low-dose esketamine delivered after labor improves post-delivery depression in women with prenatal depression.

    Study: Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. Image Credit: christinarosepix / ShutterstockStudy: Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. Image Credit: christinarosepix / Shutterstock

    Background

    Perinatal depression is common among women, particularly in low-income nations, and has negative consequences for both the mother and her child. Mothers with depression frequently feel anxiety, weaker connections, and lower attachment. Their kids are more likely to experience behavioral and emotional issues, as well as long-term psychological and developmental disorders. Poor physical health, a lack of social support, a low socioeconomic level, insufficient education, and a history of violent exposure are all risk factors for prenatal depression.

    Prenatal depression is a primary predictor of postnatal depression, and pharmacological therapies are occasionally required. Esketamine, a rapid-onset antidepressant, offers potential advantages for treatment-resistant depression, but its effect on women with perinatal depression is unknown. Previous studies have mainly focused on cesarean births, omitting moms who are depressed or at high risk of developing depression after delivery.

    About the study

    In the present randomized, placebo-controlled, double-blinded, controlled trial, researchers evaluated whether low-dose esketamine administered immediately after birth lowers depression in moms suffering from prenatal depression for 42 days.

    The researchers conducted the trial at five hospitals across China between June 19, 2020, and August 3, 2022. They included pregnant women aged 18 years and above with mild, moderate, or severe prenatal depression [defined as Edinburgh postnatal depression scale (EPDS] scores equal to or above 10) hospitalized for delivery. They excluded women with pre-pregnancy mood disorders, severe pregnancy complications, physical status III or higher, or contraindications to ketamine or esketamine use, such as severe cardiovascular disease, refractory hypertension, or hyperthyroidism. Exclusion criteria included American Society of Anesthesiologists (ASA) physical status III or higher.

    The researchers randomized the individuals in a 1:1 ratio to the esketamine group (0.20 mg per kg body weight) or placebo group, with drugs administered intravenously during the initial 40 minutes post-delivery while clipping the birth cord. The primary research outcomes were major depressive events after 42 days of delivery, identified using mini-international neuropsychiatric interviews.

    Secondary study outcomes included EPDS scores on days one and 42 after childbirth and the Hamilton Depression Rating Scale (HDRS) score 42 days after delivery. The researchers monitored adverse occurrences until 24 hours after delivery. They used logistic regression to determine the relative risk (RR) values. They used imputed missing primary outcome data in post-hoc sensitivity analyses.

    The researchers measured anxiety using the Zung self-rating anxiety scale, social assistance using the social support rating scale, marital satisfaction using the ENRICH (evaluation and nurturing relationship issues, communication, and happiness) scale, and agitation-sedation using the Richmond agitation-sedation scale. Maternal data included epidural analgesia acceptance, delivery style, fluid infusion, and blood loss, as well as the use of additional analgesics and sedatives. Bodyweight, sex, Apgar scores at one and five minutes after delivery, and initial destination were all recorded.

    Results

    The researchers screened 14,243 women and randomly assigned 364 to the study groups. The average participation age was 32 years. After 42 days, 12 (6.7%) esketamine recipients and 46 (25%) placebo recipients experienced a severe depressive episode (RR 0.3). After accounting for missing data, 14 (7.7%) of esketamine recipients and 46 (25%) of placebo recipients experienced severe depressive episodes (RR 0.3). The protocol analysis yielded comparable results.

    Esketamine-treated women had lower EPDS scores on day 7 and day 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4). Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.

    Esketamine-treated women had lower EPDS scores on day seven and 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4). Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.

    Overall, the study found that a single modest dosage of 0.2 mg/kg of esketamine administered soon after childbirth reduces major depressive events among women with prenatal depressive symptoms by almost three-quarters at 42 days postpartum. Esketamine increased the frequency of neuropsychiatric symptoms, but they were brief and lasted <24 hours, requiring no medication. The antidepressant effect of low-dose esketamine appears to continue longer in women with prenatal depression than in the overall population with depression. Further analysis is required to establish whether the reaction continues after 42 days.

    Journal reference:

    • Shuo Wang et al., Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial, BMJ 2024;385:e078218, DOI: 10.1136/bmj-2023-078218, https://www.bmj.com/content/385/bmj-2023-078218

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  • Low dose esketamine injection after childbirth reduces postpartum depression

    Low dose esketamine injection after childbirth reduces postpartum depression

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    A single low dose injection of esketamine given immediately after childbirth reduces major depressive episodes in individuals with depressive symptoms during pregnancy (prenatal depression), finds a clinical trial published by The BMJ today.

    The results suggest that low dose esketamine should be considered in new mothers with prenatal depressive symptoms.

    Depression is common during pregnancy and shortly after giving birth and can have several adverse effects on new mothers and their infants.

    Esketamine is made from a drug called ketamine. It’s used as an anesthetic and to treat depression, yet the effect for mothers with perinatal depression is unclear.

    To examine this further, researchers based in China and the USA wanted to find out if a single low dose injection of esketamine given just after childbirth might reduce subsequent depression in mothers with pre-existing prenatal depression.

    Their findings are based on 361 mothers (average age 32 years) enrolled from five Chinese hospitals from June 2020 to August 2022 with no medical history of depression and no diagnosis of depression in pregnancy, but who had scores on a scale consistent with mild prenatal depression and were preparing for childbirth. 

    None of the participants had severe pregnancy complications, or any condition that meant they couldn’t be given esketamine.

    Information on factors including age, weight (BMI), education level, family income and existing health conditions was recorded at the start of the trial and participants were randomly assigned to either esketamine or placebo intravenously infused over 40 minutes after childbirth.

    Participants were interviewed 18 to 30 hours after giving birth and again at 7 and 42 days. 

    Major depressive episode was diagnosed with the Mini-International Neuropsychiatric Interview at 42 days. Depression was also assessed using the Edinburgh depression score at 7 and 42 days, and the Hamilton Depression Rating Scale score at 42 days. No participant took antidepressants or received psychotherapy during the follow-up period.

    At 42 days after giving birth, 12 of 180 (6.7%) of mothers given esketamine experienced a major depressive episode compared with 46 of 181 (25.4%) of those given placebo (a relative risk reduction of about three-quarters). 

    As expected, mothers given esketamine had lower Edinburgh depression scores at 7 and 42 days, and a lower Hamilton depression score at 42 days.

    Based on these figures, the researchers estimate that, for every five mothers given esketamine, one major depressive episode would be prevented.

    More neuropsychiatric adverse events such as dizziness and diplopia (double vision) occurred with esketamine (45% v 22%). However, symptoms lasted less than a day and none needed drug treatment. 

    The researchers acknowledge that excluding mothers with pre-pregnancy mood disorders may have affected the validity of their results, and the short follow-up period may have led to under-reporting of neuropsychiatric symptoms and other adverse events.

    What’s more, most participants had only mild prenatal depressive symptoms, so it’s unclear whether esketamine is equally effective in those with more severe depressive symptoms.

    Nevertheless, they conclude that for mothers with prenatal depressive symptoms, a single low dose of esketamine given shortly after childbirth decreases major depressive episodes at 42 days postpartum by about three quarters. 

    These results are generally consistent with previous work investigating the effects of low dose ketamine or esketamine on postpartum depression, mainly in mothers after cesarean delivery, and, importantly, the researchers say their trial “extends existing understanding by targeting women with pre-existing prenatal depression, who were therefore at high risk of postnatal depression.”

    As such, they conclude that low dose esketamine should be considered in mothers with symptoms of prenatal depression.

    Source:

    Journal reference:

    Wang, S., et al. (2024). Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ. doi.org/10.1136/bmj-2023-078218.

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  • Study confirms the mental health benefits of weight training for older individuals

    Study confirms the mental health benefits of weight training for older individuals

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    Weight training can help reduce body fat and increase muscle strength and mass in older people, contributing to functional autonomy and avoidance of falls and injury. Furthermore, recent studies have shown that it can also benefit the mental health of older people, especially those who suffer from anxiety and depression.

    These benefits were confirmed by a study reported in the journal Psychiatry Research. The study involved a systematic review and meta-analysis of more than 200 articles on the subject. The analysis was conducted by Paolo Cunha, a postdoctoral fellow with a scholarship from FAPESP at the Albert Einstein Jewish-Brazilian Institute of Education and Research (IIEPAE) in São Paulo, Brazil. 

    “Resistance training has been shown to be one of the most effective non-pharmacological strategies for healthy aging. It promotes countless health benefits, including improvements to mental health,” Cunha said.

    The findings of the study are highly promising, he continued. Besides improvements to symptoms of anxiety and depression in the general population, weight training appears to have a more significant effect on people with a confirmed diagnosis of anxiety or depression disorder.

    “Epidemiological studies have shown that the decrease in muscle strength and mass that occurs naturally as we age may be associated with an increase in mental health problems, given the existence of various physiological mechanisms that bring about functional and structural changes and that are controlled by the brain,” Cunha said.

    Another important mental health benefit, he added, is that when weight training is done in a group, it contributes to more social interaction among those involved.

    Recommended exercises

    The investigation also pointed to the best ways of structuring one’s training to improve mental health. “How the training is done appears to influence the results achieved. The information obtained so far suggests that older people should ideally do weight training exercises three times a week, with three sets of each exercise and sessions that are not too long – six exercises would seem to be sufficient. Do less, but do it well: a short set produces better results. This is meaningful information, as we lack guidelines with specific recommendations for resistance training that focuses on mental health parameters,” Cunha said.

    While there are many possible ways to prescribe resistance training programs designed to improve the health, autonomy and quality of life for older people, most result directly or indirectly in improvements to symptoms of anxiety and depression, regardless of the intensity and volume of the exercises involved, according to Edilson Cyrino, last author of the article and principal investigator for the study. He is a professor at the State University of Londrina (UEL) and coordinates the Active Aging Longitudinal Study, a project begun in 2012 to analyze the impact of resistance training on parameters relating to the health of older women.

    Another point observed by the researchers was that the use of training machines and free weights appears to be more beneficial for mental health than exercises that involve elastic bands or calisthenics (using the weight of the person’s body), for example. 

    We don’t have statistics comparing the two kinds of training, but the analysis showed that resistance training with weights and other gear is more effective in terms of improving the mental health of older people, largely because the intensity and volume of the exercises can be more precisely controlled.”


    Paolo Cunha, postdoctoral fellow, Albert Einstein Jewish-Brazilian Institute of Education and Research (IIEPAE), São Paulo, Brazil

    In the article, the researchers note that despite the incontestable mental health benefits of weight training, important gaps remain and should be filled by further studies. “Generally speaking, most studies have involved a small number of volunteers, which hinders an understanding of how the phenomenon occurs and the main mechanisms that explain it. This research field has expanded in recent years and has ample room for more advances,” Cunha said.

    Cunha is currently conducting a project in partnership with the Research Group on Clinical Intervention and Cardiovascular Disease (GEPICARDIO) at the Albert Einstein Jewish Brazilian Hospital (HIAE) to analyze the impact of long periods of sedentarism on vascular and cognitive functions in older people.

    Source:

    São Paulo Research Foundation (FAPESP) 

    Journal reference:

    Cunha, P. M., et al. (2024). Can resistance training improve mental health outcomes in older adults? A systematic review and meta-analysis of randomized controlled trials. Psychiatry Research. doi.org/10.1016/j.psychres.2024.115746.

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  • Study shows association between childhood loneliness and first-episode psychosis

    Study shows association between childhood loneliness and first-episode psychosis

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    A new study suggests that children who felt lonely for more than 6 months before the age of 12 are more likely to experience an episode of psychosis than children who did not, with women more affected than men.

    Psychosis refers to a collection of symptoms that affect a person’s mind, where there has been some loss of contact with reality. During an episode of psychosis, a person may have difficulty recognising what is real and what is not. Symptoms of psychosis include hallucinations, delusions and confused thoughts. In some instances, psychosis may be a symptom of other mental health conditions, such as schizophrenia, bipolar disorder, or severe depression. Symptoms of schizophrenia are often categorised as positive (any change in behaviour or thoughts, such as hallucinations or delusions), negative (where people appear to withdraw from the world around them).

    Loneliness is defined as the subjective feeling of distress associated with a lack of meaningful relationships, regardless of the amount of social contact, whereas social isolation is defined as the objective lack of social contact or support.

    In an observational, case-control study, researchers assessed loneliness in children with the question “Have you ever felt lonely for more than 6 months before the age of 12” and differentiated this from social isolation by using the ‘peer relationships’ item from the Premorbid Adjustment Scale. The study sample comprised 285 patients who had experienced their first episode of psychosis and 261 controls.

    Key findings from the study include:

    • Loneliness in childhood was associated with an increased likelihood of experiencing a psychotic episode (adjusted odds ratio; aOR: 2.17, 95% CI [1.40-3.51], p=.002) and this association remained significant after controlling for objective social isolation in childhood (aOR:2.70, IC 95% [1.58-4.62], p<.001).

    • The association between loneliness and experiencing a psychotic episode was stronger in women (aOR:4.74, 95% CI [2.23-10.05], p<.001) than in men (aOR:1.17, IC 95% [0.63-2.19], p=.623).

    • In women who had experienced a psychotic episode, loneliness in childhood was associated with a significantly reduced likelihood of being diagnosed with schizophrenia spectrum disorders (aOR:0.155, 95% CI [0.048-0.506], p=.002) relative to other forms of psychosis.

    • In those who had experienced a psychotic episode, loneliness in childhood was associated with a greater severity of positive psychotic symptoms as well as affective symptoms (disturbance of mood) and worse functioning.

    Dr Covadonga Díaz-Caneja of the Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain, said “There is increasing evidence of the negative health and social consequences of loneliness in adults, but much less is known about the long-term effects of loneliness in young people. Despite their preliminary nature, our results suggest that childhood loneliness may serve as an early risk factor for later psychotic disorders and support its role as a potential target for preventive mental health interventions from an early age. This may be especially relevant considering that childhood loneliness is a prevalent phenomenon that appears to be increasing in recent years”.

    This study offers valuable insight into the association between childhood loneliness and first-episode psychosis. With the rise of digitalisation and social isolation, loneliness has become a pervasive issue affecting young individuals. The compelling findings of this study, which establish a direct connection between childhood loneliness and the onset of psychosis, highlight a concerning trend and underscore the importance of addressing social connectedness and emotional well-being from an early age.”


    Professor Andrea Fiorillo, President Elect of the European Psychiatric Association

    The European Congress of Psychiatry takes place from 6-9 April 2024 in Budapest, Hungary, and represents Europe’s largest congress dedicated to psychiatry, with over 4000 participants: epa-congress.org.

    Source:

    European Psychiatric Association

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