Tag: depression

Categories : Mental Health Metabolic DisordersTags :

Feeling Depressed Linked to Short-term Increase in Bodyweight

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Increases in symptoms of depression are associated with a subsequent increase in bodyweight when measured one month later, new research from the University of Cambridge has found.

The study, published in PLOS ONE, found that the increase was only seen among people with overweight or obesity, but found no link between generally having greater symptoms of depression and higher bodyweight.

Research has suggested a connection between weight and mental health – with each potentially influencing the other – but the relationship is complex and remains poorly understood, particularly in relation to how changes in an individual’s mental health influence their bodyweight over time.

To help answer this question, researchers at Cambridge’s Medical Research Council (MRC) Epidemiology Unit examined data from over 2,000 adults living in Cambridgeshire, UK, who had been recruited to the Fenland COVID-19 Study.

Participants completed digital questionnaires on mental wellbeing and bodyweight every month for up to nine months during the COVID-19 pandemic (August 2020 – April 2021) using a mobile app developed by Huma Therapeutics Limited.

Questions assessed an individual’s symptoms of depression, anxiety and perceived stress.

A higher score indicated greater severity, with the maximum possible scores being 24 for depression, 21 for anxiety and 40 for stress.

The team then used statistical modelling to explore whether having poorer mental wellbeing than usual was related to changes in bodyweight one month later.

The researchers found that for every increment increase in an individual’s usual score for depressive symptoms, their subsequent weight one month later increased by 45g.

This may seem small but would mean, for example, that in an individual whose depressive symptoms score rose from five to 10 (equal to an increase from ‘mild’ to ‘moderate’ depressive symptoms) it would relate to an average weight gain of 225g (0.225kg).

This effect was only observed in those individuals with overweight (defined as BMI 25-29.9kg/m2) or with obesity (BMI of over 30kg/m2). Individuals with overweight had on average an increase of 52g for each increment point increase from their usual depressive symptoms score and for those with obesity the comparable weight gain was 71g.

The effect was not seen in those individuals with a healthy weight.

First author Dr Julia Mueller from the MRC Epidemiology Unit said: “Overall, this suggests that individuals with overweight or obesity are more vulnerable to weight gain in response to feeling more depressed. Although the weight gain was relatively small, even small weight changes occurring over short periods of time can lead to larger weight changes in the long-term, particularly among those with overweight and obesity.

“People with a high BMI are already at greater risk from other health conditions, so this could potentially lead to a further deterioration in their health. Monitoring and addressing depressive symptoms in individuals with overweight or obesity could help prevent further weight gain and be beneficial to both their mental and physical health.”

The researchers found no evidence that perceived stress or anxiety were related to changes in weight.

Senior author Dr Kirsten Rennie from the MRC Epidemiology Unit said: “Apps on our phones make it possible for people to answer short questions at home more frequently and over extended periods of time, which provides much more information about their wellbeing. This technology could help us understand how changes in mental health influence behaviour among people with overweight or obesity and offer ways to develop timely interventions when needed.”

Although previous studies have suggested that poor mental health is both a cause and consequence of obesity, the research team found no evidence that weight predicted subsequent symptoms of depression.

The research was supported by the Medical Research Council.

The original text of this story is licensed under Creative Commons CC BY-SA 4.0.

Source: University of Cambridge.  Note: Content may be edited for style and length.

Journal Reference:

  1. Julia Mueller, Amy L. Ahern, Rebecca A. Jones, Stephen J. Sharp, Alan Davies, Arabella Zuckerman, Benjamin I. Perry, Golam M. Khandaker, Emanuella De Lucia Rolfe, Nick J. Wareham, Kirsten L. Rennie. The relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study. PLOS ONE, 2024; 19 (1): e0295117 DOI: 10.1371/journal.pone.0295117
Categories : Mental HealthTags :

Psychologists Reveal Magicians’ Secret Trick: A Low Risk of Depression

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Magicians are less likely to suffer from the mental health challenges faced by other creative people, like musicians and comedians, according to a new study published in the journal BJPsych Open. From comedians like Robin Williams, to poets and painters like Sylvia Plath and Van Gogh, many famous names have had well-publicised mental health disorders.

While not fully understood, there is growing evidence of a link between these health challenges and creativity. This new research led by Aberystwyth University shows that on some key measures, magicians are apparently an exception to this trend.

The study measured the psychological traits of 195 magicians and 233 people from the general population and compared with data from other creative groups. The academics’ work shows that on three key measures of psychosis or degrees of losing contact with reality, magicians are significantly less likely to suffer than artists, musicians and comedians. Magicians were less likely than all other creatives to have unusual experiences, such as hallucinations or cognitive disorganisation, which can make it hard to concentrate. Indeed, on many measures magicians appear to be less prone to these conditions than the general population. Their mental health profiles are most similar to those of mathematicians and scientists.

Dr Gil Greengross from the Department of Psychology at Aberystwyth University commented: “There is a common perception that many creative people have mental illnesses, and such illnesses make them more creative. This is the first study to show a creative group with lower scores on psychotic traits than the general population. Our research shows that members of at least one creative group, magicians, do not exhibit higher levels of mental disorders. The results demonstrate that the association between creativity and psychopathology is more complex than previously thought, and different kinds of creative work could be associated with either high or low psychoticism or autistic traits.

“The study highlights the unique characteristics of magicians, and the possible myriad associations between creativity and mental disorders among creative groups. One thing that distinguishes magicians from most other performing artists is the precision required in their performances. So, compared to other performers, it is more difficult to overcome errors. Magic tricks are largely ‘all or nothing’ acts that culminate in an ‘aha’ moment of surprise and awe. Failed magic tricks leave a greater impact than unfunny jokes, and are harder to compensate for, as they are few and far between. So, in addition to requiring highly technical skills, regardless of the type of magic performed, the high stakes of magic performances make magicians a unique creative group to study amongst all artistic professions.”

Dr Greengross from Aberystwyth University added: “What distinguishes magicians from most other creative people is that they not only create their own magic tricks but also perform them, while most creative groups are either creators or performers. For example, poets, writers, composers and choreographers create something that will be consumed or performed by others. In contrast, actors, musicians and dancers perform and interpret the creation of others. Magicians, like comedians and singer-songwriters, are one of the rare groups that do both.

“Magicians scored low on impulsive nonconformity, a trait that is associated with anti-social behaviour and lower self-control. These traits are valuable for many creative groups such as writers, poets and comedians whose creative acts are often edgy and challenge conventional wisdom. Magicians can also be equally innovative and push the limits of what is thought to be possible in magic, such as David Copperfield’s famous flying illusion. However, many magicians perform familiar tricks or some variations of them without feeling the need to innovate.”

Source: Aberystwyth University

Categories : Genetics Mental HealthTags :

Scientists Identify Stress-linked Gene in Treatment-resistant Depression

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It has long been appreciated that major depressive disorder (MDD) has genetic as well as environmental influences. In a new study in Biological Psychiatry, researchers identify a gene that interacted with stress to mediate aspects of treatment-resistant MDD in an animal model.

Jing Zhang, PhD, at Fujian Medical University and senior author of the study, said, “Emerging evidence suggests that MDD is a consequence of the co-work of genetic risks and environmental factors, so it is crucial to explore how stress exposure and risk genes co-contribute to the pathogenesis of MDD.”

To do that, the authors used a mouse model of stress-induced depression called chronic social defeat stress (CSDS) in which mice are exposed to aggressor mice daily for two weeks. They focused on a gene called LHPP, which interacts with other signalling molecules at neuronal synapses. Increased expression of LHPP in the stressed mice aggravated the depression-like behaviours by decreasing expression of BDNF and PSD95 by dephosphorylating two protein kinases, CaMKIIα and ERK, under stress exposure.

Dr Zhang noted, “Interestingly, LHPP mutations (E56K, S57L) in humans can enhance CaMKIIα/ERK-BDNF/PSD95 signaling, which suggests that carrying LHPP mutations may have an antidepressant effect in the population.”

MDD is an extremely heterogeneous condition. Differences in the types of depression experienced by people influence the way they respond to treatment. A large subgroup of people with depression fail to respond to standard antidepressant medications and have “treatment-resistant” symptoms of depression. These patients often respond to different medications, such as ketamine or esketamine, or to electroconvulsive therapy. Notably, esketamine markedly alleviated LHPP-induced depression-like behaviours, whereas the traditional drug fluoxetine did not, suggesting that the mechanism might underlie some types of treatment-resistant depression.

John Krystal, MD, Editor of Biological Psychiatry, said of the work, “We have limited understanding of the neurobiology of treatment-resistant forms of depression. This study identifies a depression risk mechanism for stress-related behaviours that fail to respond to a standard antidepressant but respond well to ketamine. This may suggest that the risk mechanisms associated with the LHPP gene shed light on the poorly understood biology of treatment-resistant forms of depression.”

Dr Zhang added, “Together, our findings identify LHPP as an essential player driving stress-induced depression, implying targeting LHPP as an effective strategy in MDD therapeutics in the future.”

Source: Elsevier

Categories : Mental Health NeurologyTags :

The Eyes may Hold the Secret to the Greatest Benefits from TMS Therapy

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A pair of recently published studies from researchers at UCLA Health suggest that measuring changes in how pupils react to light could help predict recovery from depression and personalise transcranial magnetic stimulation (TMS) treatment of major depressive disorder.

TMS is a safe, non-invasive therapy that uses magnetic fields to stimulate parts of the brain involved in mood regulation. While TMS is proven effective, not all patients respond equally well to the therapy. The ability to predict who will benefit most could allow doctors to better customise and target treatments.

In two recent studies, UCLA scientists found that the pupil’s response to light before treatment correlated with improvements in depression symptoms over the course of therapy. Pupil size reflects activation of the autonomic nervous system, which controls involuntary functions and is negatively impacted in people with depression.

The first study, appearing in the Journal of Affective Disorders, reports on outcomes for 51 patients who underwent daily TMS sessions. Before receiving treatment, researchers measured the patients’ baseline pupillary constriction amplitude, or CA: how much the pupil shrinks when exposed to light. The pupil’s constriction is an indicator of parasympathetic nervous system function. The researchers found a significant association between baseline pupil constriction amplitude and symptom improvement, indicating that a greater constriction amplitude at baseline was associated with a better outcome. In other words, those with larger pupil constriction in response to light at baseline showed greater symptom improvement over their full treatment.

The second study, published in Brain Stimulation, went further and compared patients who were treated for depression with one of two common TMS protocols: 10Hz stimulation and intermittent theta burst stimulation (iTBS). In 10Hz stimulation, magnetic pulses are delivered in a continuous and relatively high-frequency stimulation. iTBS is a faster form of stimulation with bursts of three pulses at 50Hz, repeated with short breaks between bursts. This pattern is thought to mimic the natural rhythm of certain brain activities.

The researchers found that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10Hz treatment.

“These results suggest we may be able to use a simple test of the pupil to identify who is most likely to respond to electromagnetic stimulation of the brain to treat their depression,” said researcher Cole Citrenbaum, lead author of both studies.

Tailored TMS treatments

The researchers propose that measuring pupillary reactivity before starting TMS could guide treatment selection. “Additionally, we may be able to tailor the frequency of stimulation to the individual patient to maximise their benefit from treatment,” Citrenbaum said.

“At the present time, about 65% of patients treated with TMS have a substantial improvement in their depression,” said Dr Andrew F. Leuchter, senior author of both studies. “Our goal is to have more than 85% of patients fully recover from depression. As we better understand the complex brain activity underlying depression, we move closer to matching patients with the treatments that ensure their full recovery. Pupil testing may be one useful tool in reaching this goal.”

The studies add to growing evidence on the benefits of biologically-based personalization in treating major depression. UCLA researchers plan further trials to confirm the value of pupillometry in optimizing transcranial magnetic stimulation.

Source: University of California – Los Angeles Health Sciences

Categories : Exercise Mental HealthTags :

Can Running Beat Antidepressants as a Treatment for Depression?

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The first study to compare effects of antidepressants with running exercises for anxiety, depression and overall health shows that they have about the same benefits for mental health, with health benefits for those assigned to running.

Professor Brenda Penninx from Vrije University, Amsterdam, presented the work at the ECNP conference in Barcelona (after recent publication in the Journal of Affective Disorders). Prof Penninx said, “We wanted to compare how exercise or antidepressants affect your general health, not just your mental health.”  

The 16-week course of running over the same period scores higher in terms of physical health improvement, whereas antidepressants lead to a slightly worse physical condition, as has been suggested by previous studies.  However, the drop-out rate was much higher in the group which initially chose exercise.

The researchers studied 141 patients with depression and/or anxiety. They were offered a choice of treatment; SSRI antidepressants for 16 weeks, or group-based running therapy for 16 weeks. 45 chose antidepressants, with 96 participating in running. The members of the group which chose antidepressants were slightly more depressed than the members of the group which chose to take running.

Professor Penninx said, “This study gave anxious and depressed people a real-life choice, medication or exercise. Interestingly, the majority opted for exercise, which led to the numbers in the running group being larger than in the medication group.”

Treatment with antidepressants required patients to adhere to their prescribed medication intake but this generally does not directly impact on daily behaviours. In contrast, exercise directly addresses the sedentary lifestyle often found in patients with depressive and anxiety disorders by encouraging persons to go outside, set personal goals, improve their fitness and participate in a group activity.  

The antidepressant group took the SSRI Escitalopram for 16 weeks. The running group aimed for two to three closely supervised 45-minute group sessions per week (over 16 weeks). The adherence to the protocol was lower in the running group (52%) than in the antidepressant group (82%), despite the initial preference for running over antidepressants.

At the end of the trial, around 44% % in both groups showed an improvement in depression and anxiety, however the running group also showed improvements in weight, waist circumference, blood pressure, and heart function, whereas the antidepressant group showed a tendency towards a slight deterioration in these metabolic markers.

“Both interventions helped with the depression to around the same extent. Antidepressants generally had worse impact on body weight, heart rate variability and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate for instance. We are currently looking in more detail for effects on biological aging and processes of inflammation’,” Prox Benninix said.

Physical activity is a good option, but antidepressants still have a role

Prof Benninx noted that it is not a case of one or the other when it comes to treating depression. “It is important to say that there is room for both therapies in care for depression. The study shows that lots of people like the idea of exercising, but it can be difficult to carry this through, even though the benefits are significant. We found that most people are compliant in taking antidepressants, whereas around half of the running group adhered to the two-times-a-week exercise therapy. Telling patients to go run is not enough. Changing physical activity behaviour will require adequate supervision and encouragement as we did by implementing exercise therapy in a mental health care institution.”

She added: “Antidepressants are generally safe and effective. They work for most people. We know that not treating depression at all leads to worse outcomes; so antidepressants are generally a good choice. Nevertheless, we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them. Our results suggest that implementing exercise therapy is something we should take much more seriously, as it could be a good – and maybe even better – choice for some of our patients.  

“In addition, let’s also face potential side effects our treatments can have. Doctors should be aware of the dysregulation in nervous system activity that certain antidepressants can cause, especially in patients who already have heart problems. This also provides an argument to seriously consider tapering and discontinuing antidepressants when depressed or anxious episodes have remitted. In the end, patients are only truly helped when we are improving their mental health without unnecessarily worsening their physical health.”

Source: EurekAlert!

Categories : Mental Health PaediatricsTags :

Is There a Risk of Manic Episodes in Children Taking Antidepressants?

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Mania is a possible but rare side effect of treatment with antidepressant medication in adults, but there is little known about its occurrence in children and adolescents. A newly published paper in JAMA Psychiatry investigated this, finding no evidence of mania/hypomania induced by antidepressants by 12 weeks after treatment initiation. However, caution is necessary in treatment for children with more severe depression or where a parent has bipolar disorder.

“In children and adolescents with unipolar depression, we did not find evidence of antidepressant-induced mania/hypomania by 12 weeks after treatment initiation”, says first author Suvi Virtanen, postdoctoral researcher at Karolinska Insitutet. “This corresponds to the timeframe for antidepressants to exert their psychotropic effect and when treatment-induced mania is expected to emerge. Hospitalisations, parental bipolar disorder, and the use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania.”

Antidepressants are increasingly prescribed to paediatric patients with unipolar depression (as opposed to bipolar depression which is seldom diagnosed in childhood), but little is known about the risk of treatment-emergent mania (ie, the transition from depression into mania shortly after the initiation of antidepressant treatment). Previous research suggests paediatric patients may be particularly vulnerable to this adverse outcome. The results provide complementary information to randomised clinical trials (RCTs) from a large cohort of patients treated in a real-world setting.

The researchers conducted a register-based study on children and adolescents, aged 4–17, diagnosed with unipolar depression between 2006 and 2019. They applied the emulation of target trial framework to guide the study design and analysis, reducing the bias of observational studies and mimicking a RCT.

Antidepressant treatment was unrelated to the risk of mania/hypomania, suggesting other characteristics are more relevant when evaluating which patients may have an increased risk of switching from unipolar depression into mania. “Our model using administrative information from several national registers had a moderate predictive ability, suggesting it is possible to identify patients at high risk for mania/hypomania with a prognostic clinical prediction model. The model has potential to be improved in later work”, says senior author Zheng Chang, Principal Researcher at the Department of Medical Epidemiology and Biostatistics.

Source: Karolinska Institute

Categories : Mental Health NeurologyTags :

Aripiprazole Improves Sleep in Psychiatric Disorders by Entrainment to Light/Dark Cycles

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Researchers in Japan have shown that the commonly prescribed antipsychotic drug aripiprazole helps reduce sleep disruptions in patients with certain psychiatric disorders by improving their natural entrainment to light and dark cycles. Their findings are published in Frontiers in Neuroscience.

Many patients with psychiatric conditions, such as bipolar disorder and major depressive disorder, frequently experience disruptions in their sleep–wake cycles. Research has shown that the administration of aripiprazole, a commonly prescribed antipsychotic drug, alleviates the symptoms of circadian sleep disorders in these patients. This improvement may be attributed to the effects of aripiprazole on the circadian central clock, specifically the hypothalamic suprachiasmatic nucleus (SCN), which regulates various circadian physiological rhythms, including the sleep–wake cycle, in mammals. However, the precise mechanism through which aripiprazole addresses these sleep disorder symptoms remains elusive.

Researchers from the University of Tsukuba have discovered that aripiprazole can directly affect the mammalian central circadian clock; specifically, it can modulate the photic entrainment in mice. Located in the hypothalamic suprachiasmatic nucleus (SCN), the central circadian clock comprises clock neurons that synchronize with each other, maintaining a roughly 24-hour rhythm. Simultaneously, SCN is receptive to external inputs like light, aligning itself with the environmental light-dark cycle. The researchers have found that aripiprazole disrupts the synchronization among the clock neurons in the SCN, heightening the responsiveness of these neurons to light stimuli in mice. Additionally, aripiprazole influences intracellular signalling within the SCN by targeting the serotonin 1A receptor, a prominent receptor in the SCN.

These findings suggest that the efficacy of aripiprazole in alleviating circadian rhythm sleep disorder symptoms in psychiatric patients might be attributed to the modulation of the circadian clock by the drug. This study expands the potential clinical usage of aripiprazole as a treatment for circadian rhythm sleep disorders.

Source: University of Tsukuba

Categories : Injury & Trauma Mental HealthTags :

Depression from Traumatic Brain Injury may be a Distinct Disease

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A new study suggests that depression after traumatic brain injury (TBI) could be a clinically distinct disorder rather than traditional major depressive disorder. The findings, which are published in Science Translational Medicine, hold important implications for patient treatment.

“Our findings help explain how the physical trauma to specific brain circuits can lead to development of depression. If we’re right, it means that we should be treating depression after TBI like a distinct disease,” said corresponding author Shan Siddiqi, MD, from Brigham and Women’s Hospital,. “Many clinicians have suspected that this is a clinically distinct disorder with a unique pattern of symptoms and unique treatment response, including poor response to conventional antidepressants – but until now, we didn’t have clear physiological evidence to prove this.”

Siddiqi, who led the study, was motivated by a patient he shared with David Brody, MD, PhD, a co-author on the study and a neurologist at Uniformed Services University. The two started a small clinical trial that used personalised brain mapping to target brain stimulation as a treatment for TBI patients with depression. In the process, they noticed a specific pattern of abnormalities in these patients’ brain maps.

The current study included 273 adults with TBI, usually from sports injuries, military injuries, or car accidents. People in this group were compared to other groups who did not have a TBI or depression, people with depression without TBI, and people with posttraumatic stress disorder. Study participants went through a resting-state functional connectivity MRI, a brain scan that looks at how oxygen is moving in the brain. These scans gave information about oxygenation in up to 200 000 points in the brain at about 1000 different points in time, leading to about 200 million data points in each person. Based on this information, a machine learning algorithm was used to generate an individualised map of each person’s brain.

The location of the brain circuit involved in depression was the same among people with TBI as people without TBI, but the nature of the abnormalities was different. Connectivity in this circuit was decreased in depression without TBI and was increased in TBI-associated depression. This implies that TBI-associated depression may be a different disease process, leading the study authors to propose a new name: “TBI affective syndrome.”

“I’ve always suspected it isn’t the same as regular major depressive disorder or other mental health conditions that are not related to traumatic brain injury,” said Brody. “There’s still a lot we don’t understand, but we’re starting to make progress.”

With so much data, the researchers were not able to do detailed assessments of each patient beyond brain mapping. To overcome this limitation, investigators would like to assess participants’ behaviour in a more sophisticated way and potentially define different kinds of TBI-associated neuropsychiatric syndromes.

Siddiqi and Brody are also using this approach to develop personalized treatments. Originally, they set out to design a new treatment in which they used this brain mapping technology to target a specific brain region for people with TBI and depression, using transcranial magnetic stimulation (TMS). They enrolled 15 people in the pilot and saw success with the treatment. Since then, they have received funding to replicate the study in a multicentre military trial.

“We hope our discovery guides a precision medicine approach to managing depression and mild TBI, and perhaps even intervene in neuro-vulnerable trauma survivors before the onset of chronic symptoms,” said Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine, and co-author on the study.

Source: Brigham and Women’s Hospital

Categories : Cancer Mental HealthTags :

Robust Analysis Challenges the Link Between Cancer and Anxiety and Depression

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Depression and anxiety are thought to increase a person’s risk of developing cancer, but research results have been inconclusive. In an analysis of multiple studies from the Netherlands, the UK, Norway, and Canada, investigators found that depression and anxiety are not linked to higher risks for most types of cancer among this population. The analysis is published in the journal CANCER.

Experts have suspected that depression and anxiety may increase cancer risk by affecting a person’s health-related behaviours or by having biological effects on the body that support cancer development. Some research has supported an association between depression, anxiety, and cancer incidence, while other investigations have found no or negligible associations.

To provide additional insights, Lonneke A. van Tuijl, PhD, of the University Medical Center Groningen, and her colleagues examined data from the international Psychosocial Factors and Cancer Incidence consortium, which includes information from 18 prospective study groups with more than 300 000 adults from the Netherlands, the United Kingdom, Norway, and Canada.

The team found no associations between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers during a follow-up of up to 26 years. The presence of depression or anxiety was linked with a 6% higher risk of developing lung cancer and smoking-related cancers, but this risk was substantially reduced after adjusting for other cancer-related risk factors including smoking, alcohol use, and body mass index. Therefore, this analysis supports the importance of addressing tobacco smoking and other unhealthy behaviours including those that may develop as a result of anxiety or depression.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” said Dr van Tuijl. “However, further research is needed to understand exactly how depression, anxiety, health behaviours, and lung cancer are related.”

Source: Wiley

Categories : Mental HealthTags :

Generic Ketamine Performs Strongly for Treatment-resistant Depression

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A low-cost version of ketamine to treat severe depression has performed strongly in a placebo-controlled double-blind trial. Results published in the British Journal of Psychiatry showed that more than one in five participants achieved total remission from their symptoms after a month of bi-weekly injections, while a third had their symptoms improve by at least 50%.

“For people with treatment-resistant depression – so those who have not benefitted from different modes of talk-therapy, commonly prescribed antidepressants, or electroconvulsive therapy – 20 per cent remission is actually quite good,” lead researcher Professor Colleen Loo says.

“We found that in this trial, ketamine was clearly better than the placebo – with 20 per cent reporting they no longer had clinical depression compared with only 2 per cent in the placebo group. This is a huge and very obvious difference and brings definitive evidence to the field which only had past smaller trials that compared ketamine with placebo.”

How the trial worked

The researchers, led by UNSW Sydney and the affiliated Black Dog Institute, recruited 179 people with treatment-resistant depression. All were given an injection of either a generic form of ketamine that is already widely available in Australia as a drug for anaesthesia and sedation – or placebo. Participants received two injections a week in a clinic where they were monitored for around two hours while acute dissociative and sedative effects wore off, usually within the first hour. The treatment ran for a month and participants were asked to assess their mood at the end of the trial and one month later.

In this double-blind trial, a placebo was chosen that also causes sedation, to improve treatment masking. Midazolam is a sedative normally administered before a general anaesthetic, while in many previous studies the placebo was saline.

“Because there are no subjective effects from the saline, in previous studies it became obvious which people were receiving the ketamine and which people received placebo,” Prof Loo says.

“In using midazolam – which is not a treatment for depression, but does make you feel a bit woozy and out of it – you have much less chance of knowing whether you have received ketamine, which has similar acute effects.”

Other features of the recent trial that set it apart from past studies included accepting people into the trial who had previously received electroconvulsive therapy (ECT).

“People are recommended ECT treatment for their depression when all other treatments have been ineffective,” Prof. Loo says.

“Most studies exclude people who have had ECT because it is very hard for a new treatment to work where ECT has not.”

Another difference about this trial was that the drug was delivered subcutaneously (injected into the skin) rather than by drip, thus greatly reducing time and medical complexity. The study is also the largest in the world to date that compares generic ketamine with placebo in treating severe depression.

Much more affordable

Apart from the positive results, one of the standout benefits of using generic ketamine for treatment-resistant depression is that it is much cheaper than the patented S-ketamine nasal spray currently in use in Australia. Where S-ketamine costs about AUS$800 (R9 600) per dose, the generic ketamine is a mere fraction of that, costing as little as AUS$5 (R60), depending on the supplier and whether the hospital buys it wholesale. On top of the cost for the drug, patients need to pay for the medical care they receive to ensure their experience is safe – which at Black Dog Institute clinics, comes to AUS$350 (R4200) per session.

“With the S-ketamine nasal spray, you are out of pocket by about AUS$1200 for every treatment by the time you pay for the drug and the procedure, whereas for generic ketamine, you’re paying around AUS$300-350 for the treatment including the drug cost,” Prof Loo says.

She adds that for both S-ketamine and generic ketamine treatments, the positive effects often wear off after a few days to weeks, so ongoing treatment may be required, depending on someone’s clinical situation. But the prohibitive costs of the drug and procedure make this an unsustainable proposition for most.

The researchers will next be looking at larger trials of generic ketamine over longer periods, and refining the safety monitoring of treatment.

Source: University of New South Wales