Clozapine Refractory Colonic Pseudo-Obstruction

The article discusses a case of clozapine-induced refractory colonic pseudo-obstruction in a patient with treatment-resistant schizophrenia (TRS), emphasizing the need for monitoring and potentially early surgical intervention due to severe gastrointestinal effects. Here's a summary of the key points:

- **Background**: Clozapine, an atypical antipsychotic used for TRS, has well-known hematological adverse effects requiring close monitoring. However, its gastrointestinal side effects, particularly on bowel motility, are less recognized but can lead to severe conditions like colonic pseudo-obstruction, necessitating total colectomy.
- **Case Presentation**: A 60-year-old female with TRS developed refractory colonic pseudo-obstruction, chronic ischemic colitis, and eventually required emergency total colectomy and end ileostomy after presenting with symptoms of fevers, hypotension, tachycardia, vomiting, overflow diarrhea, and reduced consciousness.
- **Treatment and Outcome**: Despite aggressive non-operative management including oral aperients, phosphate fleet enemas, neostigmine infusions, and optimization of electrolytes, the patient's condition did not improve. Surgical intervention was ultimately necessary due to the severe and life-threatening nature of her gastrointestinal complications.
- **Discussion**: Clozapine's anticholinergic effects lead to decreased gastrointestinal motility, increasing the risk for conditions like colonic pseudo-obstruction and stercoral colitis. The case underscores the importance of monitoring clozapine's gastrointestinal side effects and considering early surgical options in refractory cases.
- **Conclusions**: Clinicians should closely monitor patients on clozapine for gastrointestinal hypomotility and other adverse effects. Preventative measures and early intervention are crucial to avoid severe outcomes like the need for total colectomy.

This case highlights the critical need for awareness and proactive management of the gastrointestinal side effects of clozapine to prevent potentially life-threatening conditions.

Siriwardena D et al. Cureus. 2024

Dementia Prevention for Rheumatoid Arthritis Pt

Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects millions worldwide, potentially increasing the risk of developing dementia, a condition with significant social and economic impact. The link between RA and dementia suggests that inflammation plays a crucial role in both conditions. This has led scientists to explore whether medications used to treat RA, known as disease-modifying antirheumatic drugs (DMARDs), could also influence the risk of developing dementia.

A comprehensive review of existing research, involving nearly a million RA patients, discovered intriguing insights. The study found that patients treated with biological DMARDs (bDMARDs), which are advanced therapies targeting specific components of the immune system, had a notably lower risk of developing dementia compared to those on conventional synthetic DMARDs (csDMARDs), which are traditional medications used to treat RA. Specifically, the risk reduction was about 24% for those on TNF inhibitors, a type of bDMARD, and similarly for other non-TNF biologics.

Interestingly, different types of TNF inhibitors showed varying levels of effectiveness in reducing dementia risk, with etanercept being the most effective, followed by adalimumab and infliximab. This suggests that not all bDMARDs are equal in their potential neuroprotective effects. However, the study found no significant reduction in dementia risk for RA patients taking csDMARDs, like methotrexate or hydroxychloroquine, except for sulfasalazine, which was associated with an increased risk of dementia.

These findings highlight the possibility that bDMARDs, especially TNF inhibitors, might offer protective benefits against dementia in RA patients. This has important implications for selecting RA treatments for patients at high risk of dementia and suggests a new avenue for research into dementia prevention and treatment. Further clinical trials are needed to explore the neuroprotective potential of TNF inhibitors and other bDMARDs, potentially opening up new strategies for combating dementia.

Xie W et al. RMD Open. 2024

Cholesterol & Brain Health

Dyslipidemia, a condition marked by abnormal levels of blood lipids, has been scrutinized for its connection to cognitive impairments, such as memory loss and difficulty in thinking. In simpler terms, scientists have been exploring whether having high levels of bad cholesterol or fats in your blood might influence your brain's ability to function properly. 

A comprehensive review of numerous studies, involving more than 750,000 individuals, has shed light on this issue. The findings suggest that individuals with dyslipidemia are more prone to experiencing cognitive difficulties. Specifically, high total cholesterol levels were identified as a significant risk factor for cognitive impairment. Interestingly, this risk seemed to be more pronounced in older individuals and men. 

On the flip side, high levels of triglycerides, another type of fat in the blood, were surprisingly associated with a lower risk of cognitive disorders. However, the relationship between high levels of low-density lipoprotein cholesterol (often referred to as "bad" cholesterol) and cognitive impairment was not clear-cut, with the evidence suggesting no direct link.

These insights are crucial as they underscore the importance of managing cholesterol levels not just for heart health but also for maintaining cognitive function, especially as we age. The study suggests that tailored strategies to regulate lipid levels could potentially mitigate the risk of developing cognitive impairments in individuals at risk due to dyslipidemia. 

In essence, this research highlights the complex interplay between blood lipids and brain health, suggesting that what's good for the heart might also be beneficial for the brain.

Zhao Y et al. J Integr Neurosci. 2024

Thyroid Dysfunction & Alzheimer's Disease

In recent research, scientists have been delving into the complex relationship between thyroid dysfunction and Alzheimer's disease (AD), uncovering a potential vicious cycle connecting the two conditions. The thyroid, a key gland in our endocrine system, plays a vital role in our central nervous system's development and function, affecting everything from our neurons to our memory. When thyroid function is disrupted—either producing too much hormone (hyperthyroidism) or not enough (hypothyroidism)—it can lead to significant health issues, including cognitive impairments that overlap with those seen in Alzheimer's disease.

Alzheimer's disease, a form of dementia, progressively deteriorates the brain, leading to memory loss, confusion, and other severe cognitive declines. Interestingly, both hyperthyroidism and hypothyroidism have been linked to an increased risk of developing AD. This connection is thought to be due to the broad range of effects that thyroid hormones have on the brain, including their influence on neuron health, synaptic plasticity (the brain's ability to form new connections), and the accumulation of proteins that are typically found in AD-affected brains.

The article suggests a "vicious circle" where thyroid dysfunction and Alzheimer's disease may exacerbate each other. For instance, thyroid dysfunction can lead to brain changes that resemble those seen in AD, such as neuron death and misfolded protein deposition. Conversely, AD can disrupt the body's regulation of thyroid hormones, potentially leading to thyroid dysfunction. This interplay suggests that each condition might accelerate the progression of the other, creating a cycle that could worsen both thyroid health and cognitive function over time.

Moreover, the article highlights the potential for treating thyroid dysfunction as a way to mitigate or possibly improve cognitive decline in AD patients. While current treatments for thyroid dysfunction can help with some symptoms, they do not fully reverse the cognitive impairments associated with AD. This underscores the complexity of AD and the need for more research to fully understand how best to treat or prevent it.

In summary, the research underscores the intricate link between thyroid health and brain function, particularly in the context of Alzheimer's disease. It suggests that maintaining balanced thyroid hormone levels could be crucial in preserving cognitive health and preventing or slowing the progression of neurodegenerative diseases like AD. As we continue to explore this connection, it becomes increasingly clear how interconnected our body's systems are and the importance of holistic approaches to health and medicine.

Li Z et al. Front Endocrinol (Lausanne). 2024

Constipation in Intellectual Disabilities

Chronic constipation is a prevalent and concerning issue among individuals with intellectual disabilities, affecting up to half of this population. This condition not only causes discomfort but can also lead to severe health complications and even premature death. A recent cross-sectional study sought to uncover the risk factors contributing to chronic constipation in individuals with intellectual disabilities living in the community.

The study involved distributing a questionnaire to the carers of people with intellectual disabilities who are under the care of four specialist intellectual disability services in England. This questionnaire was designed to identify potential risk factors for constipation.

The findings revealed that 42% of the 181 participants reported experiencing chronic constipation, which is defined as having two or fewer bowel movements per week or taking regular laxatives three or more times weekly. The study identified several significant risk factors associated with chronic constipation in this group:

- **Severity of Intellectual Disability:** Individuals with more severe intellectual disabilities were more likely to suffer from chronic constipation.
- **Dysphagia:** Difficulty swallowing was linked to a higher risk of constipation.
- **Cerebral Palsy:** Those with cerebral palsy showed a higher incidence of constipation.
- **Poor Mobility:** Limited mobility was a significant factor associated with constipation.
- **Polypharmacy:** The use of multiple medications, especially antipsychotics and antiseizure medications, was closely linked to constipation.
- **Toileting Support:** A greater need for support with toileting was associated with a higher risk of constipation.

Interestingly, the study found no significant associations between chronic constipation and factors such as age or gender, indicating that the risk factors are more closely related to the level of disability and associated health conditions.

The conclusions drawn from this study highlight the need for closer monitoring and proactive management of bowel health in individuals with intellectual disabilities, particularly those with severe disabilities, dysphagia, cerebral palsy, poor mobility, and those requiring substantial toileting support. Reducing the use of medications that may contribute to constipation, where possible, was also identified as a crucial, modifiable risk factor. The researchers suggest that by using the constipation questionnaire to screen patients, healthcare providers can implement individualized bowel care plans, potentially reducing the incidence and impact of chronic constipation in this vulnerable population.

Laugharne R et al. BJPsych Open. 2024

New Study Sheds Light on Antidepressants & MS

This study delves into the effects of two different antidepressants, vortioxetine and fluoxetine, on metabolic parameters in patients with Major Depressive Disorder (MDD). Recognizing that MDD can increase the risk of developing metabolic syndrome (MS), a condition that includes a cluster of cardiovascular risk factors, this research is particularly significant. While there's been concern about the metabolic side effects of atypical antipsychotics, the impact of selective serotonin reuptake inhibitors (SSRIs) like fluoxetine on metabolic syndrome has been less clear.

The research was designed as a prospective, open-label, randomized controlled trial, where participants were assigned to receive either fluoxetine (20 mg) or vortioxetine (10 mg) daily. The study aimed to monitor changes in metabolic syndrome parameters over 24 weeks, including fasting plasma glucose (FPG), triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, waist circumference, and blood pressure.

Here's a breakdown of the findings:

- **Fasting Plasma Glucose (FPG):** Significant improvement was observed in the vortioxetine group (group A) at week eight when compared with the fluoxetine group (group B).
- **Triglycerides (TGs):** Both groups showed higher levels of triglycerides, but the study highlights a significant improvement at week 16 in group A.
- **High-Density Lipoprotein (HDL):** HDL levels improved significantly in group A by week 20.
- **Waist Circumference:** A significant reduction was noted in group A at week 24.
- **Blood Pressure:** No significant differences were found between the two groups in terms of systolic and diastolic blood pressure.
- **Depression Remission Rates:** Depression remission rates, measured by the Hamilton Depression Rating Scale (HAM-D), and medication adherence were similar in both groups, indicating that both medications were equally effective in treating MDD.

The study concludes that vortioxetine might offer a better profile in terms of certain metabolic parameters such as fasting glucose, HDL cholesterol, and waist circumference compared to fluoxetine, without compromising the effectiveness of depression treatment. However, both medications led to an increase in triglyceride levels, and neither had a significant impact on blood pressure.

These findings suggest that vortioxetine could be a preferable option for treating depression in patients at risk of metabolic syndrome, but the overall choice of antidepressant should consider both the psychiatric condition and the metabolic health of the patient. This study adds valuable insights into the complex interplay between antidepressant medication and metabolic health, underscoring the importance of holistic patient care.

Sankar K et al. Cureus. 2024

Intersection of Bipolar Disorder and T1DM

This case report shines a light on a fascinating and complex interaction between bipolar disorder, its treatment, and type 1 diabetes mellitus—a condition where the body cannot produce insulin and requires lifelong management including insulin therapy and continuous monitoring of blood sugar levels. The focus of this study is on a 41-year-old woman living with both bipolar II disorder and type 1 diabetes. She made a significant health decision: to stop her long-term mood-stabilizing medication, quetiapine, which is known to have metabolic side effects including impacting blood sugar levels.

What's particularly intriguing about this case is what happened to her blood sugar patterns before and after she stopped taking quetiapine. Using real-time continuous glucose monitoring—a method that provides a detailed picture of glucose levels throughout the day—the researchers discovered that while on quetiapine, despite its potential to negatively affect metabolism, her glucose levels were more stable and closer to normal. After discontinuing the medication, her glucose levels became higher and more variable.

This observation is critical for several reasons. First, it suggests that managing bipolar disorder with appropriate medication might also help stabilize blood sugar levels in patients with comorbid type 1 diabetes. The emotional instability, impulsivity, and stress associated with untreated bipolar disorder can lead to erratic eating and self-care behaviors, negatively impacting diabetes management and glucose control. This case underscores the potential "bipolar diabetes" phenomenon, where the interaction between bipolar disorder and diabetes can exacerbate both conditions, leading to a cycle of worsening mental and physical health.

The case report emphasizes the need for a holistic approach to treatment, considering both psychiatric and somatic aspects of health. For patients with comorbid conditions like bipolar disorder and type 1 diabetes, this means closely monitoring the impact of psychiatric medications not just on mental health symptoms but also on blood sugar control. It also highlights the potential for continuous glucose monitoring to play a role in tailoring psychiatric treatments to individual metabolic responses, paving the way for more personalized and effective care strategies.

Ultimately, this case adds to the growing body of evidence suggesting that mental health and physical health are deeply interconnected. It calls for further research into the bidirectional relationships between psychiatric disorders and metabolic diseases, which could lead to innovative approaches in clinical practice that improve outcomes for patients living with these complex comorbidities.

Breznoscakova D et al. Front Endocrinol (Lausanne). 2024

Understanding Fibromyalgia and the Impact of MH

 Fibromyalgia (FM) is a condition that causes widespread pain and fatigue, and it often coexists with psychiatric disorders. Researchers have been exploring the connection between the psychological aspects of fibromyalgia and its treatment outcomes, particularly in response to medications known as serotonin and norepinephrine reuptake inhibitors (SNRIs). SNRIs are a class of drugs commonly used to treat fibromyalgia, depression, and anxiety, among other conditions.

A study conducted between December 2020 and November 2022 aimed to deepen our understanding of this connection. It looked into the variety of psychological symptoms present in people with fibromyalgia and investigated how these symptoms might influence the effectiveness of SNRI treatment.

Participants included 30 fibromyalgia patients who responded well to SNRIs, 32 patients who did not respond to SNRIs, and 30 healthy individuals without fibromyalgia. To assess their psychological state, participants completed several questionnaires designed to measure levels of depression, anxiety, anhedonia (the inability to feel pleasure), symptoms of bipolar disorder, and experiences of dissociation.

The findings revealed that those with fibromyalgia who did not respond to SNRI treatment had higher levels of depression, anxiety, and anhedonia compared to those who did respond to the treatment. Moreover, a significant proportion of the non-responsive group showed scores indicative of an anxiety disorder.

This indicates that the severity of certain psychological symptoms, such as depression, anxiety, and anhedonia, can predict how well a person with fibromyalgia might respond to SNRI medications. The study suggests that integrating psychological assessments into the standard care for fibromyalgia could be beneficial. This approach could help tailor treatment plans more effectively, considering both the physical and psychological aspects of fibromyalgia, to improve outcomes for patients.

Krupa AJ et al. Psychiatr Pol. 2024

COVID-19 and the Risk of Pulmonary Aspergillosi

In recent times, a new challenge has emerged in the fight against COVID-19: a fungal infection known as COVID-19-associated pulmonary aspergillosis (CAPA). This complication can be serious and even fatal for those with severe cases of COVID-19. Recognizing the importance of identifying those at risk, a thorough review and analysis have been conducted to pinpoint the factors that might increase a patient's likelihood of developing CAPA.

Researchers sifted through thousands of studies, eventually focusing on 27 that met their criteria, involving a total of 6,848 COVID-19 patients. Of these, 1,324 (19.3%) were diagnosed with CAPA. Through their meticulous work, they identified eight major risk factors for CAPA:

1. **Pre-existing comorbidities**, including chronic liver disease, hematological malignancies (like leukemia), chronic obstructive pulmonary disease (COPD), and cerebrovascular disease (related to blood flow in the brain).
2. **The use of invasive mechanical ventilation**, highlighting the increased risk for those needing assistance with breathing.
3. **Renal replacement therapy** (like dialysis), indicating kidney issues as a contributing factor.
4. **Treatment with interleukin-6 inhibitors and corticosteroids**, which are used to reduce inflammation but may inadvertently increase the risk of infections.

Additionally, it was found that patients with CAPA were generally older and required mechanical ventilation for longer periods than those without CAPA. Unfortunately, CAPA also correlated with a higher mortality rate.

This analysis points to the potential of using targeted antifungal prophylaxis, or preventive treatment, in high-risk COVID-19 patients to mitigate the risk of developing CAPA. Identifying these risk factors is a crucial step toward better managing and treating severe COVID-19 cases, ensuring that patients receive the most appropriate and effective care.

Francesca Gioia et al. THE LANVET Respiratory Medicine. 2024.

Breaking Down the Complexities of FEP

Understanding how psychosis affects the mind, especially before any treatment begins, is crucial for developing effective care. A recent comprehensive review delved into this by examining people experiencing their first episode of psychosis (FEP) who have not yet received any antipsychotic medications. The aim was to measure how their cognitive functions—like memory, attention, and problem-solving—compare to those of healthy individuals, without the complicating effects of medication.

Researchers scoured PubMed for studies on this topic and analyzed data from fifty studies, involving over 2,500 individuals with FEP and nearly 3,000 healthy controls. They looked into various cognitive areas using a standard set of tests known for assessing cognitive function in schizophrenia and related disorders.

The findings were significant. Across all areas of cognitive function tested—ranging from how fast people process information, to verbal and visual learning, working memory, attention, problem-solving, and executive functions (like planning and flexibility)—those with FEP showed substantial impairments compared to healthy controls. The differences weren't minor; they were marked and consistent across all cognitive domains.

Moreover, there was a notable variability within the FEP group itself. This means that while, on average, individuals with FEP struggle more with cognitive tasks than healthy individuals, the degree of struggle varies widely among them. Some may face relatively minor challenges, while others may experience profound difficulties that could significantly affect their daily lives and long-term outcomes.

This variability underscores a critical point: identifying individuals with more severe cognitive impairments early on could be key. These individuals might benefit most from targeted interventions like cognitive remediation therapies, which aim to improve cognitive functions. The findings highlight the importance of early cognitive assessment in psychosis care, aiming not just at treating psychosis symptoms but also at addressing cognitive impairments to improve overall outcomes and quality of life.

Lee M et al. JAMA Psychiatry. 2024