Tag: depression

Long-term usage of antidepressant medications may protect from dementia

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Long-term treatment with certain antidepressants appeared associated with reduced dementia incidence, according to results of a case-control study published in Journal of Clinical Psychiatry.

“Depression could represent one of these potentially modifiable risk factors for all-cause dementia,” Claudia Bartels, PhD, of the department of psychiatry and psychotherapy at University Medical Center Goettingen in Germany, and colleagues wrote. “Numerous studies have concordantly demonstrated a strong association between depression and an increased risk [for] subsequent dementia. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depressive symptoms in [Alzheimer’s disease] dementia.

“Preclinical research in recent years has suggested that SSRIs reduce amyloid plaque burden in transgenic mouse models of [Alzheimer’s disease] and in cognitively healthy humans, attenuate amyloid-[beta]1-42–induced tau hyperphosphorylation in cell culture and improve cognition in mice.”

However, the effects of SSRIs on cognition in Alzheimer’s disease dementia were linked mostly to negative results in randomized clinical trials; research is sparse regarding which antidepressants may influence risk for developing dementia; and evidence is particularly rare for treatment duration effects on this risk. Thus, Bartels and colleagues sought to determine the effects of antidepressant drug classes and individual compounds with various treatment durations on the risk for developing dementia. The researchers analyzed data of 62,317 individuals with an incident dementia diagnosis who were included in the German Disease Analyzer database, and they compared outcomes to those of controls matched by age, sex and physician. They conducted logistic regression analyses, which were adjusted for health insurance status and comorbid diseases linked to dementia or antidepressant use, to evaluate the association between dementia incidence and treatment with four major classes of antidepressant drug, as well as 14 of the most commonly prescribed individual antidepressants.

Results showed an association between treatment for 2 years or longer with any antidepressant and a lower risk for dementia vs. short-term treatment among 17 of 18 comparison. Particularly for long-term treatment, herbal and tricyclic antidepressants were linked to a decrease in incidence of dementia. Long-term treatment with escitalopram (OR = 0.66; 95% CI, 0.5-0.89) and Hypericum perforatum (OR = 0.6; 95% CI, 0.51-0.7) were associated with the lowest risks for dementia on an individual antidepressant basis.

“Clinical trials — although well acknowledged as the gold standard procedure — have debunked numerous promising compounds and become increasingly challenging with longer treatment durations,” Bartels and colleagues wrote. “Thus, and in awareness of the controversy of this suggestion, analyzing data from registries in a naturalistic setting may be an attractive and feasible alternative. If individual datasets could be combined in a multinational effort, even more powerful analyses of merged big databases could be performed and an additive contribution with naturalistic data could be made.”

https://www.healio.com/news/psychiatry/20200828/longterm-treatment-with-certain-antidepressants-may-reduce-dementia-incidence

Regular Exercise Helps Patients Combat Cancer

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OUTRUNNING CANCER: Tumors on the lungs of sedentary mice (left) and animals that ran on wheels (right) after injection with melanoma cells.
L. PEDERSEN ET AL., CELL METAB, 2016

Bente Klarlund Pedersen

Mathilde was diagnosed with breast cancer at the age of 44. Doctors treated her with surgery, chemotherapy, and radiation, and Mathilde’s physician informed her that, among many other side effects of her cancer treatment, she could expect to lose muscle mass. To fight muscle wasting, Mathilde began the intensive physical training program offered to cancer patients at the Rigshospitalet University Hospital of Copenhagen. The program consists of 3.5-hour sessions of combined resistance and aerobic training, four times a week for six weeks. Although the chemotherapy made her tired, Mathilde (a friend of mine, not pictured, who requested I use her first name only) did not miss a single training session.

“In a way it felt counterintuitive to do intensive, hard training, while I was tired and nauseous, but I was convinced that the training was good for my physical and mental health and general wellbeing,” Mathilde told me in Danish. She followed the chemo- and radiotherapy strictly according to the prescribed schedule. She was not hospitalized, acquired no infections, and did not develop lymphedema, a failure of the lymphatic system that commonly occurs following breast cancer surgery and leads to swelling of the limbs.

Physical exercise is increasingly being integrated into the care of cancer patients such as Mathilde, and for good reason. Evidence is accumulating that exercise improves the wellbeing of these patients by combating the physical and mental deterioration that often occur during anticancer treatments. Most remarkably, we are beginning to understand that exercise can directly or indirectly fight the cancer itself.

An increasing amount of epidemiological literature strongly indicates that exercise training may lower the risk of cancer, control disease progression, amplify the effects of anticancer therapy, and improve physical function and psychosocial outcomes. For example, a 2016 study of more than 1.4 million individuals in the US and Europe found that people could reduce their cancer risk with moderate to vigorous leisure-time exercise training. The phenomenon held across several different cancers, including breast, colon, rectum, esophagus, lung, liver, kidney, bladder, and head and neck. And the combined results of approximately 700 unique exercise intervention trials, involving more than 50,000 cancer patients in total, leave little doubt that patients benefit from physical activity, showing improvements such as reduced toxicity of anticancer treatment, decreased disease progression, and enhanced survival. The same studies showed that exercise training improves mood, decreases loss of muscle mass, and helps cancer patients return to work earlier after successful treatment. Some studies show that 150 minutes per week of moderate exercise nearly double the chance of survival compared with breast cancer patients who don’t exercise during treatment.

Hundreds of animal studies, conducted over decades, suggest that the link is likely causal: in mice and rats, exercise leads to a reduction in the incidence, growth rate, and metastatic potential of cancer across a large variety of models of different human and murine tumor types. But how exercise helps fight cancer is a bit of a black box. Exercise may improve the efficacy of anticancer treatment by boosting the immune system and thereby attenuating the toxicity of chemotherapy and immunotherapy. Cancer patients are also likely to benefit from the overall health-promoting properties of physical activity, such as improved metabolism and enhanced cardiovascular function.

Uncovering the mechanisms whereby exercise induces anticancer effects is crucial to fighting the disease. Exercise-related factors that have a direct or indirect anticancer effect could serve as valuable biomarkers for monitoring the amount, intensity, and type of exercise required to best aid cancer treatment. Such research could also potentially highlight novel therapeutic targets.

Each workout matters

Regardless of the nature of the training, the primary setting of exercise’s effect on cancer is the bloodstream. Long-term training has been associated with a reduction in the blood levels of systemic risk factors, such as sex hormones, insulin, and inflammatory molecules. However, this effect is only seen if exercise training is accompanied by weight loss, and researchers have not yet established causal direct links between regular exercise training and the reductions in the basal levels of these risk factors. Alternatively, the anticancer effect of exercise could also be the result of something that occurs within individual sessions of exercise, during which muscles are known to release spikes of various hormones and other factors into the blood.

To learn more about the effects of individual bouts of exercise versus long-term training regimens, Christine Dethlefsen, a graduate student in my laboratory, incubated breast cancer cells with serum obtained from cancer survivors at rest before and after a six-month training intervention that began after patients completed primary surgery, chemotherapy, and radiotherapy. For comparison, she incubated other cells with serum obtained from blood drawn from these patients immediately after a two-hour acute exercise session during their weeks-long course of chemotherapy. Her study revealed that serum obtained following an exercise session reduced the viability of the cultured breast cancer cells, while serum drawn at rest following six months of training had no effect.

These data suggest that cancer-fighting effects are driven by repeated acute exercise, and each bout matters. In Dethlefsen’s study, incubation with serum obtained after a single bout of exercise (consisting of 30 minutes of warm-up, 60 minutes of resistance training, and a 30-minute high-intensity interval spinning session) reduced breast cancer cell viability by only 10 to 15 percent compared with control cells incubated with serum obtained at rest. But a reduction in tumor cell viability by 10 to 15 percent several times a week may add up to clinically significant inhibition of tumor growth. Indeed, in a separate study, my colleagues and I found that daily, voluntary wheel running in mice inhibits tumor progression across a range of tumor models and anatomical locations, typically by more than 50 percent.

Exercise’s molecular messengers

One prime candidate for helping to explain the link between exercise and anticancer effects is a group of peptides known as myokines, which are produced and released by muscle cells. Several myokines are released only during exercise, and some researchers have proposed that these exercise-dependent myokines contribute to the myriad beneficial effects of physical activity for all individuals, not just cancer patients, perhaps by mediating crosstalk between the muscles and other parts of the body, including the liver, bones, fat, and brain.

Exercise’s Anticancer Mechanisms

Researchers are beginning to understand that not only can exercise improve cancer patients’ overall wellbeing during treatment, but it may also fight the cancer itself. Experiments on cultured cells and in mice hint at some of the mechanisms that may be involved in these direct and indirect effects.

1) Exercising muscles release multiple compounds known as myokines. Several of these have been shown to affect cancer cell proliferation in culture, and some, including interleukin-6, slow tumor growth in mice.

2) Exercise stimulates an increase in levels of the stress hormones epinephrine and norepinephrine, which can both act directly on tumors and stimulate immune cells to enter the bloodstream.

3) Epinephrine also stimulates natural killer cells to enter circulation.

4) In mice, interleukin-6 appears to direct natural killer cells to home in on tumors.

5) In lab-grown cells and in mice, epinephrine, norepinephrine, and some myokines hinder tumor growth and metastasis.

The best-characterized myokine is interleukin-6, levels of which increase exponentially during exercise in humans. At least in mice, interleukin-6 is involved in directing natural killer (NK) cells to tumor sites. But there are approximately 20 known exercise-induced myokines, and the list continues to grow. Preliminary studies show that myokines can reduce cancer growth in cell culture and in mice. For example, when treated with irisin, a myokine best known for its ability to convert white fat into brown fat, cultured breast cancer cells were more likely to lose viability and undergo apoptosis than were control cells. A study I led found that oncostatin M, another myokine that is upregulated in murine muscles after exercise, also inhibits breast cancer proliferation in vitro. And a team led by Toshikazu Yoshikawa of Kyoto Prefectural University determined that in a mouse model of colon cancer, a myokine known as secreted protein acidic and rich in cysteine (SPARC) reduced tumorigenesis in the colon of exercising mice. Overall, skeletal muscle cells may be secreting several hundred myokine types, but of these, only about 5 percent have been investigated for their biological effects. And researchers have tested fewer for whether they regulate cancer cell growth.

Not all of the molecular messengers released in response to exercise come from the muscles. Notably, exercise induces acute increases in epinephrine and norepinephrine, stress hormones released from the adrenal gland that are involved in recruiting NK cells in humans. Murine studies show that NK cells can signal directly to cancer cells. In Dethlefsen’s study, when breast cancer cells incubated with serum obtained after a bout of exercise were then injected into mice, they showed reduced tumor formation. The exercise-induced suppression of breast cancer cell viability and tumor formation were, however, completely blunted when we blockaded β-adrenergic signaling, the pathway through which epinephrine and norepinephrine work. These findings suggested that epinephrine and norepinephrine are responsible for the cancer-inhibiting effects we observed. Epinephrine and norepinephrine, which activate NK cells, have also been shown to act on cancer cells through the Hippo signaling pathway, which is known for regulating cell proliferation and apoptosis. Exercise-induced spikes in these stress hormones activate this pathway, which somehow inhibits the formation of new malignant tumors associated with metastatic processes.

Calling the immune system

In addition to acting directly on tumors, the myokines released during and after exercise are known to mobilize immune cells, particularly NK cells, which appear to be instrumental to the exercise-mediated control of tumor growth in mice.

The late molecular biologist Pernille Højman of the Centre for Physical Activity Research at Rigshospitalet was a leader in discerning this mechanism. In the study described above that compared tumor growth in active and sedentary mice, on which I was also an author, Højman looked more closely at the tumors and found that the running mice had twice as many cytotoxic T cells and five times more NK cells than those animals housed without a wheel.

Højman repeated the experiment on mice that had been engineered to lack cytotoxic T cells. Again, she found that mice with access to running wheels had smaller tumors. When she performed the same test on mice that had intact T cells but lacked NK cells, the tumors of all the mice grew to the same size. This suggested that the NK cells, and not the T cells, were the link between exercise and tumor growth suppression.

Work by other groups had demonstrated that epinephrine has the potential to mobilize NK cells, and Højman and the rest of our team wondered if epinephrine had a role in mediating the anticancer effects of exercise. We injected mice that had malignant melanoma with either epinephrine or saline and found that the hormone indeed reduced the growth of tumors, but to a lesser degree than what was observed in the mice that had access to a wheel. Something else had to be involved.


AND STAY OUT: Exercise activates natural killer cells (purple) and helps them home to tumors.

To find out what, our team tested the effects of interleukin-6, which we suspected was the additional exercise factor involved in tumor homing of immune cells. When we exposed inactive mice to both epinephrine and interleukin-6, the rodents’ immune systems attacked the tumors as effectively as if the animals had been running.

While much remains to be learned about how physical exercise influences cancer, evidence shows that exercise training is safe and feasible for patients with the disease and contributes to their physical and psychosocial health. (See “Exercise and Depression” on page 44.) Being active may even delay disease progression and improve survival. A growing number of patients, including Mathilde, are undergoing exercise training to fight physical deterioration during cancer treatment. As they do so, scientists are working hard to understand the pathways by which physical activity results in anticancer activity.

Exercise and Depression

Depression is a severe adverse effect of cancer and cancer therapy. The risk of depression can be as high as 50 percent for some cancer diagnoses, although this number varies a great deal depending on cancer type and stage (J Natl Cancer Inst Monogr, 32:57–71, 2004). In addition to its effects on a patient’s quality of life, depression can hinder compliance with treatment, and it’s a risk factor for mortality in cancer patients (Lancet, 356:1326–27, 2000). In recent years, healthcare providers have increasingly integrated physical exercise into the care of cancer patients with the aim of controlling disease and lessening treatment-related side effects, while researchers have amassed evidence supporting the assertion that such training can lower symptoms of depression in these patients (Acta Oncol, 58:579–87, 2019). The biological mechanisms behind this beneficial effect remain to be determined, although some clues have emerged.

For example, a study in mice found that exercise-dependent changes in metabolism result in reduced accumulation of some neurotoxic products (Cell, 159:33-45, 2014). In cancer patients, systemic levels of kynurenine, a neurotoxic metabolite associated with fatigue and depression, are upregulated (Cancer, 121:2129-36, 2015). In mice, exercise enhances the expression of the enzyme kynurenine aminotransferase, which converts kynurenine into neuroprotective kynurenic acid, thereby reducing depression-like symptoms.

Findings such as these, together with exercise’s well-documented effects in alleviating depression among patients without cancer, suggest that incorporating exercise into cancer treatment may benefit mental as well as physical health.

https://www.the-scientist.com/features/regular-exercise-helps-patients-combat-cancer-67317?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=86607989&_hsenc=p2ANqtz-8W-OrX7bn_MULo5_Jx-u7E1c2gVfZwwWCD26RHtjZT7CoZ9KWhz0zOuCD53QkfOvre5WKYWWxP0plIm4Lf56uABjYb0A&_hsmi=86607989

Children with less sleep experience increased depression and anxiety, and decreased cognitive performance

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Shorter sleep duration among children was associated with increased risk for depression, anxiety, impulsive behavior and poor cognitive performance, according to study findings published in Molecular Psychiatry.

“Sleep disturbances are common among children and adolescents around the world, with approximately 60% of adolescents in the United States receiving less than 8 hours of sleep on school nights,” Jianfeng Feng, PhD, of the department of computer science at University of Warwick in the UK, told Healio Psychiatry. “An important public health implication is that psychopathology in both children and their parents should be considered in relation to sleep problems in children. Further, we showed that brain structure is associated with sleep problems in children and that this is related to whether the child has depressive problems.”

According to Feng and colleagues, the present study is the first large-scale research effort to analyze sleep duration in children and its impact on psychiatric problems including depression, brain structure and cognition. They analyzed measures related to these areas using data from the Adolescent Brain Cognitive Development Study, which included structural MRI data from 11,067 individuals aged 9 to 11 years.

The researchers found that depression, anxiety and impulsive behavior were negatively correlated with sleep duration. Dimensional psychopathology in participants’ parents was correlated with short sleep duration in the children. Feng and colleagues noted that the orbitofrontal cortex, prefrontal and temporal cortex, precuneus and supramarginal gyrus were brain areas in which higher volume was correlated with longer sleep duration. According to longitudinal data analysis, psychiatric problems, particularly depressive problems, were significantly associated with short sleep duration 1 year later. Moreover, they found that depressive problems significantly mediated these brain regions’ effect on sleep. Higher volume of the prefrontal cortex, temporal cortex and medial orbitofrontal cortex were associated with higher cognitive scores.

“Our findings showed that 53% of children received less than 9 hours of sleep per night,” Feng said. “More importantly, the behavior problems total score for children with less than 7 hours of sleep was 53% higher on average and the cognitive total score was 7.8% lower on average than for children with 9 to 11 hours of sleep. We hope this study attracts public attention to sleep problems in children and provides evidence for governments to develop advice about sleep for children.” – by Joe Gramigna

https://www.healio.com/psychiatry/depression/news/online/%7B7440e93a-fe6a-4154-88f4-a5858d16c4cb%7D/children-with-less-sleep-experience-increased-depression-anxiety-decreased-cognitive-performance

AI is learning how to use brain scans to predict the right antidepressant for patients

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By Jason Arunn Murugesu

An AI can predict from people’s brainwaves whether an antidepressant is likely to help them. The technique may offer a new approach to prescribing medicines for mental illnesses.

Antidepressants don’t always work, and we aren’t sure why. “We have a central problem in psychiatry because we characterise diseases by their end point, such as what behaviours they cause,” says Amit Etkin at Stanford University in California. “You tell me you’re depressed, and I don’t know any more than that. I don’t really know what’s going on in the brain and we prescribe medication on very little information.”

Etkin wanted to find out if a machine-learning algorithm could predict from the brain scans of people diagnosed with depression who was most likely to respond to treatment with the antidepressant sertraline. The drug is typically effective in only a third of the people who take it.

He and his team gathered electroencephalogram (EEG) recordings showing the brainwaves of 228 people aged between 18 and 65 with depression. These individuals had previously tried antidepressants, but weren’t on such drugs at the start of the study.

Roughly half the participants were given sertraline, while the rest got a placebo. The researchers then monitored the participants’ mood over eight weeks, measuring any changes using a depression rating scale.

Brain activity patterns
By comparing the EEG recordings of those who responded well to the drug with those who didn’t, the machine-learning algorithm was able to identify a specific pattern of brain activity linked with a higher likelihood of finding sertraline helpful.

The team then tested the algorithm on a different group of 279 people. Although only 41 per cent of overall participants responded well to sertraline, 76 per cent of those the algorithm predicted would benefit did so.

Etkin has founded a company called Alto Neuroscience to develop the technology. He hopes it results in more efficient sertraline prescription by giving doctors “the tools to make decisions about their patients using objective tests, decisions that they’re currently making by chance”, says Etkin.

This AI “could have potential future relevance to patients with depression”, says Christian Gluud at the Copenhagen Trial Unit in Denmark. But the results need to be replicated by other researchers “before any transfer to clinical practice can be considered”, he says.

Journal reference: Nature Biotechnology, DOI: 10.1038/s41587-019-0397-3

Read more: https://www.newscientist.com/article/2232792-brain-scans-can-help-predict-wholl-benefit-from-an-antidepressant/#ixzz6DeyTJYpK

FDA Calls Psychedelic Psilocybin a ‘Breakthrough Therapy’ for Severe Depression

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By Yasemin Saplakoglu

The FDA is helping to speed up the process of researching and approving psilocybin, a hallucinogenic substance in magic mushrooms, to treat major depressive disorder (MDD).

For the second time in a year, the U.S. Food and Drug Administration (FDA) has designated psilocybin therapy — currently being tested in clinical trials — as “breakthrough therapy,” an action that is meant to accelerate the typically sluggish process of drug development and review. It is typically requested by a drug company and granted only when preliminary evidence suggests the drug may be an enormous improvement over already available therapy, according to the FDA.

Last year, the FDA granted “breakthrough therapy” status to psilocybin therapy in the still-ongoing clinical trials run by the company Compass Pathways, which are looking into psilocybin’s potential to treat severe treatment-resistant depression, or depression in patients who have not improved after undergoing two different antidepressant treatments, according to New Atlas.

Now, the FDA has granted another “breakthrough therapy” status to the psychedelic treatment, this time for a U.S.-based clinical trial conducted by the nonprofit Usona Institute, according to a statement from the company. This clinical trial, which includes 80 participants at seven different sites across the U.S., focuses on the efficacy of treating patients with MDD with a single dose of psilocybin.

There are more than 17 million people in the U.S. who have major depressive disorder, or severe depression that lasts more than two weeks, according to the statement. Psilocybin, with a single dose, could profoundly impact the brain and have long-lasting impacts after wiping away depressive symptoms, according to the statement.

The phase 2 trial is expected to be completed by early 2021, and with the help of this status, Usona expects it to quickly move into a larger phase 3 trial, according to New Atlas. Around one in three treatments previously given a Breakthrough Therapy status have moved on to get market approval, New Atlas wrote.

“What is truly groundbreaking is FDA’s rightful acknowledgement that MDD, not just the much smaller treatment-resistant depression population, represents an unmet medical need and that the available data suggest that psilocybin may offer a substantial clinical improvement over existing therapies,” Dr. Charles Raison, the director of clinical and translational research at Usona, said in the statement.

This isn’t the first time that a psychedelic has been researched for its potential in treating depression. In March, the FDA approved a nasal spray depression treatment for treatment-resistant patients based on Esketamine, a substance related to ketamine — an anesthetic that’s also been used as an illicit party drug. But much is still unknown even of this approved drug. Though fast-acting, it’s unclear how Esketamine changes the brain and thus what its long-term effects will be, according to a previous Live Science report.

https://www.livescience.com/psilocybin-depression-breakthrough-therapy.html

New clinical trial shows that most common antidepressant barely helps improve depression symptoms

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he most commonly prescribed antidepressant barely relieves symptoms of modern depression, a major study reveals.

The largest independent investigation ever undertaken found patients taking sertraline experienced negligible improvements in mood.

Published in the Lancet Psychiatry, the study comes amid mounting controversy over increased use of antidepressants by GPs in recent decades, with roughly 7.3 million people in England issued a prescription each year.

Its authors said they were “shocked and surprised” by the results, and called for the development of new classes of medication.

However, in the absence of better drugs, they do not want current prescribing practice to be changed because the trial also showed sertraline is effective in reducing anxiety, which often accompanies depression.

The new trial is by far the largest to be conducted without the involvement of the pharmaceutical industry.

It is also the most in-depth examination of sertraline – a type of selective serotonin reuptake inhibitor (SSRI) – in patients with a range of depression severities, rather than just in severely depressed patients in specialist mental health units.

The study included 654 people aged 18 to 74 who were given either the antidepressant for 12 weeks or a placebo.

The results showed depressive symptoms were five per cent lower after six weeks in the sertraline group, which was “no convincing evidence” of an effect.

After 12 weeks, there was a 13 per cent reduction, a finding the experts described as “weak”.

But the drug did offer clear benefits in reducing anxiety, with a 21 per cent reduction in symptoms at six weeks and 23 per cent at 12 weeks.

This is likely to explain why patients taking sertraline were twice as likely to say they felt generally better compared to the placebo group, even once questioned on specific symptoms of depression the benefit was far weaker.

Symptoms of depression include poor concentration, low mood, trouble with sleep, lack of enjoyment, whereas anxiety is presents as worry, nervousness, irritability and restlessness.

Professor Glyn Lewis, who led the research at University College London, said: “We were shocked and surprised when we did our analysis.

“There is absolutely no doubt this is an unexpected result.’

“Our primary hypothesis was that it would affect those depressive symptoms at six weeks and we didn’t find that.

“We definitely need better treatments for depression, and we need more research in this area.”

He suggested that new, more effective classes of antidepressants could be based on ketamine, psilocybin, the psychedelic in magic mushrooms, and anti-inflammatories.

It is thought that roughly four million people in England are long-term users of antidepressants.

Prescribing data shows that SSRI’s such as sertraline make up 54 per cent of antidepressant prescriptions.

Scientists have responded to the new study by pointing out that some of the patients had very mild symptoms of depression to start with, making it less likely that sertraline would cause an improvement.

However, others have pointed out that this is exactly the basis upon which GPs tend to hand out the drugs in practice.

Dr Gemma Lewis, who co-authored the new research, said: “I think it’s really important to understand that anxiety symptoms are very, very common among people with depression.”

She added: “It appears that people taking the drug are feeling less anxious, so they feel better overall, even if their depressive symptoms were less affected.

“We hope that we have cast new light on how antidepressants work, as they may be primarily affecting anxiety symptoms such as nervousness, worry and tension, and taking longer to affect depressive symptoms.”

Professor Helen Stokes-Lampard, Chair of the Royal College of GPs, said: “It is well-established that it often takes a while for patients to feel the full benefits of modern antidepressants and that they work best when taken for significant periods of time, which is one reason why doctors will often review patients after several weeks of use and then prescribe a fairly long course of the drugs, if they appear to be beneficial.”

https://www.telegraph.co.uk/science/2019/09/19/common-antidepressant-barely-helps-improve-depression-symptoms/

Thanks to Kebmodee for bringing this to the It’s Interesting community.

Hyperthermic temperament may affect 4-5% of the population

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by David N. Osser, MD

Current estimates are that 4% to 5% of the population is at risk for a disorder on the bipolar spectrum. Among the patients in the so-called soft portion of that spectrum are those with a disturbance of temperament in the direction of hypomania.

The concept of temperament is a product of German nosological research from a century ago starting with Kraepelin. In the US, the concept has been championed by Hagop Akiskal, MD and his colleagues. Akiskal is now the editor emeritus of the Journal of Affective Disorders. The notion of depressive temperament has been incorporated into DSM-5 nosology in the form of “persistent depressive disorder” (previously called dysthymia). The other pole was called hyperthymia by the Germans. DSM committees have considered adding hyperthymia but have not done so. The research base on it is still, to many, unconvincing. However, it seems that in clinical practice one encounters individuals who have chronic low-grade hypomanic symptoms—high energy, need for less sleep than others, chronic optimism, chronic risk taking. These individuals can be prone to major depressions and can become severely suicidal.

Akiskal and colleagues have been describing these patients for almost 40 years. Their research criteria for hyperthymic temperament include onset before age 21, habitual sleep of less than 6 hours even on weekends, excessive use of denial, and traits (described originally by Schneider et al) that include being overoptimistic, self-assured, grandiose, overtalkative, warm and people-seeking, uninhibited, promiscuous, and meddlesome (1). Neurobiological studies have suggested the individuals have dopaminergic dysregulation (2),

Treatment issues have focused on what medications to use when hyperthymic individuals become depressed. The studies have all been uncontrolled. However, it seems that antidepressants are ineffective for these depressions and often trigger a mixed state or frank mania at times. Mood stabilizers and medications effective for bipolar depression may be more appropriate for the depressions in these patients.Usually their sunny temperament itself doesn’t require treatment and may, in fact, foster excellent productivity and creativity during much of their lifespan.

Disclosures:
Dr Osser is a Consulting Psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA.

References:
1. Akiskal HS, Mallya G. Criteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull. 1987;23:68-73.

2. Rihmer Z, Akiskal KK, Rihmer A, Akiskal HS. Current research on affective temperaments. Curr Opin Psychiatry. 2010;23:12-18.

Cholesterol-lowering statins may also have antidepressant efficacy

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by Bruce Jancin

The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

https://www.the-hospitalist.org/hospitalist/article/207875/depression/statins-may-do-double-duty-antidepressants?channel=51329

A consortium of US universities aims to examine how best to help graduate students, a vulnerable population that is affected by anxiety and depression.

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An ambitious research project aims to assess the state of mental-health resources and support for graduate students. The 22-month initiative is a joint venture of the Council of Graduate Schools (CGS) in Washington DC and the Jed Foundation, a non-profit organization in New York City that focuses on the mental health of young adults. The initiative will explore current schemes and programmes centred on student wellness at CGS member universities in the United States and Canada, and provide recommendations for future approaches to promote mental and emotional well-being in students.

“We want to create a road map for moving forward,” says Suzanne Ortega, CGS president and the principal investigator of the project, called Supporting Mental Health and Wellness of Graduate Students. “We’ll be offering advice about policies and resources that will help students in crisis while also creating an environment where graduate students can thrive.”

The project, supported by nearly US$280,000 in grants from the Alfred P. Sloan Foundation and the Andrew W. Mellon Foundation, will gather input through surveys of administrators at CGS’s 500 or so member institutions across the world, along with focus groups that will probably involve students as well as those advocating on behalf of students. A key part of the conversation will take place at a workshop for students, administrators and mental-health specialists that is tentatively scheduled for October next year in Washington DC. An initial report of findings and recommendations for policies is scheduled to be published in December next year.

Unmet needs

The pressure, competition and stress experienced by graduate students puts them at high risk for mental-health issues, Ortega says. Precise estimates of the prevalence of anxiety and depression in this population remain elusive, she notes, and graduate students need and deserve thoughtful, evidence-based support. “We’re convinced by the need,” she says. “We know that a significant minority of graduate students have clinical symptoms of distress.”

Nance Roy, the Jed Foundation’s chief clinical officer, says that few effective mental-health programmes aimed at graduate students are currently offered at academic institutions. The Jed Foundation assisted universities in developing guidelines that will help to address undergraduate mental health, but Roy points out that graduate students have different needs and life situations that could require tailored approaches. For example, graduate students might find it especially difficult to take time off when they’re feeling overwhelmed. “They may not be able to just step away from a research project,” she says. “We want to promote people taking time off if they need it.”

Roy is also concerned about mentorship, a crucial aspect of graduate training that doesn’t always receive much scrutiny. “That relationship needs a tremendous amount of attention,” she says.

Ortega and other investigators have identified some innovative approaches that deserve a closer look. Boston University in Massachusetts, for example, instituted a holiday policy this year that ensures two weeks, or ten working days, of paid holiday every year for PhD students on annual stipends. “The idea is that this will foster work–life balance, which is a big part of student wellness,” says Ortega.

Another is the Mental Health Bill of Rights and Responsibilities that was adopted by the graduate education department at Vanderbilt University in Nashville, Tennessee, in February. The document states that, among other things, any student who seeks mental-health treatment through the university will be assigned a care coordinator who can help them to navigate the system and connect with resources.

Mark Wallace, a neuroscientist and dean of the Vanderbilt University Graduate School, says that the bill of rights was a product of many discussions between graduate students and university leaders. “This approach ensures that everyone has a role to play in tackling mental-health issues on our campus, whether they be students, faculty or staff,” he says.

Covering new ground

Ortega says that the CGS initiative is the first of its kind in the United States and Canada. She and other investigators were partly inspired by other mental-health schemes, including the UK Council For Graduate Education’s first International Conference on the Mental Health & Wellbeing of Postgraduate Researchers, which took place in May (and was supported by Nature Research).

The CGS will co-host a global summit, Cultural Contexts of Health and Well-Being in Graduate Education, at the University of Manchester, UK, on 1–3 September. “There’s a growing recognition of these issues in Europe,” Ortega says.

Ortega and Roy hope that their project will inspire universities around the United States to take a closer look at at what they’re doing — or not doing — to promote the mental health of graduate students. The results should also lay the foundation for a future of better support for graduate students, including more scientifically rigorous studies of issues that this group faces, Ortega says.

“Graduate-student mental health and well-being has become one of the hottest topics that our graduate dean members want to see addressed,” Ortega says. “Clearly, we have a lot of work to do in the next 22 months.”

https://www.nature.com/articles/d41586-019-02584-7?utm_source=Nature+Briefing&utm_campaign=0a58fd4efb-briefing-dy-20190902&utm_medium=email&utm_term=0_c9dfd39373-0a58fd4efb-44039353

Reported Symptoms of Anxiety, Hearing Voices Most Common Reasons for Misdiagnosis of Schizophrenia

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In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), researchers report that about half the people referred to the clinic with a schizophrenia diagnosis did not actually have schizophrenia. People who reported hearing voices or having anxiety were the ones more likely to be misdiagnosed, according to the study published in the Journal of Psychiatric Practice.

The researchers say that therapies can vary widely for people with schizophrenia, bipolar disorder, major depression or other serious types of mental illness, and that misdiagnosis can lead to inappropriate or delayed treatment.

The findings, the researchers say, suggest that second opinions at a specialised schizophrenia clinic after initial diagnosis are wise efforts to reduce the risk of misdiagnosis, and ensure prompt and appropriate patient treatment.

“Because we’ve shined a spotlight in recent years on emerging and early signs of psychosis, diagnosis of schizophrenia is like a new fad, and it’s a problem especially for those who are not schizophrenia specialists because symptoms can be complex and misleading,” says Krista Baker, LCPC, Johns Hopkins Medicine, Baltimore, Maryland. “Diagnostic errors can be devastating for people, particularly the wrong diagnosis of a mental disorder,” she adds.

According to the National Institute of Mental Health, schizophrenia affects an estimated 0.5% of the world population, and is more common in men. It typically arises in the late adolescences, 20s and even as late as the early 30s in women. Symptoms such as disordered thinking, hallucinations, delusions, reduced emotions and unusual behaviours can be disabling, and drug treatments often create difficult side effects.

The new study was prompted in part by anecdotal evidence among healthcare providers in Baker’s specialty clinic that a fair number of people were being seen who were misdiagnosed. These patients usually had other mental illnesses, such as depression.

To see if there was rigorous evidence of such a trend, the researchers looked at patient data from 78 cases referred to EPIC for consultation between February 2011 and July 2017. Patients were an average age of 19, and about 69% were men, 74% were white, 12% African American and 14% were another ethnicity. Patients were referred to the clinic by general psychiatrists, outpatient psychiatric centres, primary care physicians, nurse practitioners, neurologists or psychologists.

Each consultation by the clinic took 3 to 4 hours, and included interviews with the patient and the family, physical exams, questionnaires, and medical and psychosocial histories.

Of the patients referred to the clinic, 54 people came with a predetermined diagnosis of a schizophrenia spectrum disorder. Of those, 26 received a confirmed diagnosis of a schizophrenia spectrum disorder following their consultation with the EPIC team, which is composed of clinicians and psychiatrists. Of the 54 cases, 51% were rediagnosed by clinic staff as having anxiety or mood disorders. Anxiety symptoms were prominent in 14 of the misdiagnosed patients.

One of the other most common symptoms that the researchers believe may have contributed to misdiagnosis of schizophrenia was hearing voices, as almost all incorrectly diagnosed patients reported auditory hallucinations.

“Hearing voices is a symptom of many different conditions, and sometimes it is just a fleeting phenomenon with little significance,” says Russell L. Margolis, MD, Johns Hopkins Schizophrenia Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. “At other times when someone reports ‘hearing voices’ it may be a general statement of distress rather than the literal experience of hearing a voice. The key point is that hearing voices on its own doesn’t mean a diagnosis of schizophrenia.”

In speculating about other reasons why there might be so many misdiagnoses, the researchers say that it could be due to overly simplified application of criteria listed in the Diagnostic Statistical Manual of Mental Disorders, a standard guide to the diagnosis of psychiatric disorders.

“Electronic medical record systems, which often use pull-down diagnostic menus, increase the likelihood of this type of error,” says Dr. Margolis, who refers to the problem as “checklist psychiatry.”

“The big take-home message from our study is that careful consultative services by experts are important and likely underutilised in psychiatry,” says Dr. Margolis. “Just as a primary care clinician would refer a patient with possible cancer to an oncologist or a patient with possible heart disease to a cardiologist, it’s important for general mental health practitioners to get a second opinion from a psychiatry specialty clinic like ours for patients with confusing, complicated or severe conditions. This may minimise the possibility that a symptom will be missed or overinterpreted.”

Dr. Margolis cautioned that the study was limited to patients evaluated in 1 clinic. Nonetheless, he was encouraged by the willingness of so many patients, their families and their clinicians to ask for a second opinion from the Johns Hopkins clinic. If further study confirms their findings, it would lend support to the belief by the Johns Hopkins team that overdiagnosis may be a national problem, because they see patients from across the country who travel to Johns Hopkins for an opinion. They hope to examine the experience of other specialty consultation clinics in the future.

Reference: doi: 10.1097/PRA.0000000000000363

SOURCE: Johns Hopkins Medicine

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