Psychiatry’s Biggest Antidepressant Trial Just Got Reanalyzed: “It May Have Misled Treatment for Decades”, Experts Claim

 Overmedication is one of fastest rising problems in psychiatry field worldwide

New findings challenge STAR*D, the 4,000-patient government study that shaped depression treatment guidelines for years. Reanalysis shows no clear benefit of follow-up antidepressants over placebo, and experts weigh in on the need for alternative treatment methods.

 A new analysis published in the Journal of Clinical Psychopharmacology casts doubt on one of the most influential studies in modern psychiatry. When re-evaluated against randomized, placebo-controlled trials, most of the medication strategies used in the STAR*D trial, long seen as the gold standard for stepwise antidepressant care, show no measurable benefit beyond placebo.

The review compared STAR*D’s major treatment steps to real-world randomized controlled trial outcomes. Raising the SSRI dose, switching to another antidepressant, and adding common medications like bupropion or buspirone all failed to outperform placebo in blinded trials. 

The only add-on with consistent clinical benefit was lithium – which is constantly prescribed less and is harder to access due to known toxic effects on, e.g., the thyroid gland and the kidneys.  

“This study is a wake-up call,” said Dr. Hannah Nearney, clinical psychiatrist and UK Medical Director at Flow Neuroscience, a company that develops neuromodulation therapies for depression treatment. “Patients who don’t respond to the first antidepressant are often placed on a carousel of tweaks – higher doses, add-on pills, lateral switches – that produce side effects without providing real relief.”

An estimated 70% of patients with depression do not achieve remission with their first medication. Yet existing guidelines, based heavily on the STAR*D trial, still recommend drug modifications that, as reanalysis revealed, appear scientifically weak.

The new findings suggest these treatment steps may be driven more by expectation and placebo effects than by pharmacological mechanisms.

“This mirrors what we see every day in practice,” added Dr. Kultar Singh Garcha, NHS GP and Flow’s Global Medical Director. “Patients are stuck in trial-and-error cycles, not because we lack alternatives – but because those alternatives haven’t been prioritized in funding or regulation.”

One of those alternatives is transcranial direct current stimulation (tDCS) – a wearable, non-invasive brain stimulation technology backed by clinical trials. Flow Neuroscience, whose CE-certified device is already used in the NHS, says the findings highlight an urgent need to expand access to safe, proven, non-drug interventions.

“While tens of millions continue to cycle through barely effective drug combinations, validated neuromodulation therapies are still being overlooked or overregulated,” added Dr. Nearney. “We must give patients options grounded in science, and it must stay up-to-date. We’re living in a time where depression is becoming the next epidemic.”

The study’s authors argue for a rethinking of depression treatment models. As it claims, not all medications are ineffective – but the common practice of escalating doses or stacking drugs without placebo-controlled evidence may be doing more harm than good.

“This doesn’t mean medication should be abandoned,” Dr. Garcha concluded. “But if we’re going to recommend a new drug step, it has to outperform staying the course – not just look promising in an unblinded study. Otherwise, we’re replacing one flawed approach with another.”

 

ten23 health® kickstarts new era with launch of industry-first robot-assisted pilot non-GMP sterile filling in its Basel facilities

  ten23 health®, the human-centric and sustainable contract development, testing and manufacturing organization (CDTMO), today announced the launch of its “Line 0” (non-GMP) pilot sterile fill & finish services from its Basel (BASE®) facilities. The first-of-its-kind, custom-designed and purpose-built pilot sterile filling line is a co-development with Optima. The robot-based, small-scale filling machine is suitable for ready-to-use (RTU) and bulk containers, including vials, syringes, and cartridges, in combination with a 1.1 m² sized freeze-dryer (lyophiliser).

With development and preclinical costs increasingly under pressure, Line 0 offers the pharmaceutical industry an exciting new option for a wide range of key tasks. Customers will be able to take advantage of perfectly scaled-down, time- and cost-efficient process development services, and access aseptically produced drug product batches that do not require GMP grade. The pilot line avoids the extra costs and constraints of performing such activities in GMP manufacturing facilities or using non-representative equipment in labs.

“We will add significant speed and value to our customers’ projects with this innovative technology and the additional services that seamlessly integrate with our sterile GMP manufacturing offerings. We can now provide complete solutions from the development and preclinical scale to clinical and commercial manufacturing scale, with purpose-built scaling and transfer in mind,” explains Prof. Dr. Hanns-Christian Mahler, Chief Enablement Officer (CEO) at ten23 health.

Operated under the ISO9001 quality management system, Line 0 is designed to provide aseptically filled batches which may be required for specific purposes such as the implementation of novel processes or primary packaging, stability testing, analytical reference materials, and preclinical study material.

The new offering is compatible with novel primary packaging as well as related process development and characterization assessments for filling, stopper setting and lyophilization processes. It seamlessly integrates different manufacturing scales at ten23, from the new Pilot “Line 0” (non-GMP) in BASE® (Basel) to the VIVA1® and VIVA2® GMP fill& finish lines (Visp), all of which Isolators in Class C environment in Annex 1 GMP compliance:  “Line 1” (for clinical and commercial use using ready-to-use (RTU)container) “Line 2” (for large-scale commercial and possibly clinical use using RTU container), to “Line 3” (for clinical and commercial bulk-vial liquid or lyophilizate manufacturing). All sterile manufacturing lines are based on Optima equipment platforms, enabling easy scale-up and ensuring they are fit-for-purpose for the specific needs of each customer.

“With the addition of the pilot line to our offering we can support our customers by supplying liquid and lyophilized batches early on in their development timeline, with a setup and process representative of later clinical or commercial GMP batches. Compatibility with our GMP filling lines allows seamless process scaleup and reliable supply throughout our customers’ molecules’ lifecycles,” adds Dr. Susanne Jörg, Chief Customer Delivery Officer (COO) at ten23 health.

HonorHealth Research Institute presents new findings in decades-long quest to conquer aggressive pancreatic cancer

 

Promising results of RMC-6236, in combination with other drug treatments, presented at annual meeting of AACR

 

HonorHealth Research Institute’s new downtown Phoenix laboratory has produced its first study, centered on a promising new treatment for pancreatic cancer, one of the most aggressive and difficult to treat of all malignancies. Study results were presented April 29 in Chicago at the annual meeting of the 58,000-member American Association for Cancer Research (AACR), the world’s largest professional organization of cancer investigators, caregivers and patient advocates. Study findings indicate that a newly discovered drug, RMC-6236, also known as Daraxonrasib, is a powerful inhibitor of RAS (including KRAS, NRAS and HRAS). These are commonly mutated cancer-causing genes that drive the formation of many types of tumors, including pancreatic cancer.  This study evaluated the effectiveness of RMC-6236 in patient-derived pancreatic tumors harboring KRAS mutations. New: Center for Translational Science According to this initial study to emerge from the Research Institute’s new Center for Translational Science laboratory, RMC-6236, when combined with other proven pancreatic cancer drugs, is a promising new agent against RAS, particularly KRASG12X. Existing KRASG12C inhibitors are unable to target other mutations and often have the unintended result of making patient tumors drug resistant. “The fibrotic tumor microenvironment in pancreatic cancer exacerbates therapy resistance, and combining RMC-6236 with other therapies could overcome both intrinsic and acquired resistances,” according to Taylor Bargenquast, a clinical research technician and lead author of the study abstract, which she presented at AACR. “These results demonstrate the efficacy of RMC-6236 when combined with other therapeutic agents in a pancreatic cancer model — a three-dimensional model of pancreatic cancer cells derived from patient biopsies,” said Sunil Sharma, M.D., director of the Center for Translational Science and the senior author of the study abstract. “The combination of RMC-6236 with standard chemotherapy and targeted therapies enhances its antitumor activity, suggesting a promising strategy for improving therapeutic outcomes in pancreatic cancer,” said Erkut Borazanci, M.D., another of the study’s authors, and medical director of the Institute’s Oncology Research Division. 52,000 Americans expected to die Pancreatic cancer is the third-leading cause of cancer-related death in the U.S., after lung and colorectal cancers, and is expected to contribute this year to the deaths of nearly 52,000 Americans. Contributing to this study — Evaluating the efficacy of RAS(ON) inhibitor RMC-6236 combined with chemotherapy and other targeted therapies in 3D models involving patients with KRAS-mutated pancreatic cancer — was the Phoenix-based Translational Genomics Research Institute (TGen), part of City of Hope. The study suggests that human clinical trials are warranted to further evaluate the safety and effectiveness of RMC-6236.

Researchers develop virtual reality-based system to improve psychiatric diagnosis

 

Researchers have developed a virtual reality-based system that shows promise in improving the differentiation between common mental health conditions, potentially paving the way for earlier and more personalised treatment. The work is published in the March edition of the peer-reviewed journal European Neuropsychopharmacology, with a subsequent (31 March) comment also being published in the same journal.

Accurate diagnosis remains one of the biggest challenges in psychiatry, with more than half of psychiatric patients changing their diagnosis within 10 years. Most psychiatric diagnoses rely on patients reporting their symptoms, but many mental health conditions share overlapping features. For example, apathy, hallucinations, and cognitive problems may be present in both schizophrenia and bipolar disorder, making it difficult to distinguish between the two. Misdiagnosis can lead to suboptimal treatment and poorer outcomes.

 Now, a group of Danish scientists have combined virtual reality with physiological measurements (such as skin conductivity) to explore a more objective method for identifying different mental health conditions.

 Lead researcher Professor Kamilla Miskowiak (University of Copenhagen) said, “This is an important step forward. Until now, diagnosis has largely depended on self-reporting of symptoms, but our findings suggest that virtual reality scenarios combined with physiological measures may help differentiate between similar conditions. This is an area where psychiatry has long faced difficulties.”

 The researchers recruited 100 participants, including individuals with bipolar disorder, borderline personality disorder, schizophrenia, and healthy controls. Participants were exposed to various immersive virtual reality scenarios designed to elicit emotional and physiological responses, such as a video of a crying baby, a discussion in a canteen, and a cramped elevator scenario. The researchers measured emotional responses and skin conductivity during these scenarios.

 Their results indicate that these responses differed systematically between diagnostic groups, suggesting that this approach has the potential to enhance diagnostic accuracy. However, larger studies are needed to confirm these findings and to explore how such methods might be used in clinical practice.

Professor Miskowiak said, “This study is part of the VIRDIS project, which aims to develop objective tools to support psychiatric diagnosis. Our initial findings are promising, but further large-scale research is needed to validate this approach and develop it into a practical clinical tool. We are now launching a follow-up study with 300 participants and implementing machine learning methods to improve individual-level diagnostic predictions. Our long-term goal is to improve early and personalised treatment for patients with mental health disorders.”

The European Neuropsychopharmacology paper has attracted attention since it was placed online, including a published commentary from Dr Sijia Liu at the Liaoning University of Traditional Chinese Medicine, Shenyang, China, stating:
 
“This study offers a groundbreaking approach to addressing the persistent challenges in psychiatric diagnosis and treatment by leveraging virtual reality (VR) technology. I suggest that future research should consider integrating artificial intelligence algorithms to analyse the extensive data generated from these VR scenarios. I believe this work holds significant promise for advancing our understanding and clinical practices in mental health care”.  
 
This project is a collaboration between the Copenhagen Mental Health Centre, Khora Virtual Reality and EXP360. This study was supported by the Ivan Nielsen Foundation. 

Travels: Domaine les Terres Bleues: a new luxury destination in the Hautes-Vosges (France)

                   

 

Adrien Feltz and his partner Alexia Courtois embark on a new hospitality adventure with the unveiling of Domaine les Terres Bleues, a preserved haven spanning 1 hectare in the heart of the Vallée des Lacs (Vosges), designed as an ode to contemplation and relaxation.

"We wanted to create a place that brings together everything we dream of finding during our own getaways as a couple — a space where every detail invites relaxation and intimacy" the couple shares.

Designed by architect Gérald Klauss and brought to life by the Decobois company, the property consists of two prestigious chalets, each accommodating two guests. Fully oriented outward to provide a constant connection with the surrounding nature, they combine noble materials, clean lines, and large bay windows, creating perfect harmony between the indoors and outdoors. Each chalet features a private 50m2 south-facing terrace with a jacuzzi, a cozy living area with a wood-burning fireplace, a freestanding bathtub, a sensory shower, and a king-size bed.

An ideal getawat to recharge and reconnect

This is the promise of a unique experience where luxury meets simplicity and authenticity. Eacg stay becomes an invitation to slow down, refocus, and savor the present moment. The property features an outdoor pool (heated from May to October), a mirror sauna nestled in the forest, a natural spring water bath, personalized treatments and massages by experienced practitioners, wellness activities (yoga, meditation, and sophrology sessions), and outdoor adventures (guided hikes, mountain bike rides, countryside picnics, and wildlife observation).

A rich territory, alive through the seasons

Nestled in the heart of the Vosges, nature lovers will be enchanted by the diversity of the landscapes, where deer, hinds, and foxes often make appearances. Gérardmer, the jewel of the Vosges, is home to the region’s largest natural lake, of glacial origin and situated at an altitude of 660m. Nicknamed the “lake of a thousand reflections,” it’s just a few minutes from the estate, with a well-marked 6 km walking trail allowing visitors to take in its full beauty. The town is also renowned for its Fantastic Film Festival, the Daffodil Festival (a bi-annual spring event), and the richness of its natural spaces.

In winter, the ski resorts of Gérardmer and La Bresse (the largest in Eastern France) are just a 10-minute drive away. The scenic Route des Crêtes, accessible by car or bike, offers breathtaking panoramas of the Vosges mountains, valleys, and lakes.

Domaine les Terres Bleues is located just a short distance from Alsace, 45 minutes from Colmar — the perfect opportunity to explore charming Alsatian villages and wander the vineyard trails to taste local wines.

Practical Information

Opening: May 12 

Address: 560 Rte du Valtin, 88400 Xonrupt-Longemer - Vallée des Lacs, Hautes Vosges 

Website: www.domaine-lesterresbleues.com 

Instagram: www.instagram.com/domaine_les_terres_bleues/

Rates: from 450€/night

 

New independent studies show that ColdZyme addresses the root cause of respiratory infections, reducing sick days and symptoms

 Today, results from two independent studies on the medical device ColdZyme were published in the peer-reviewed scientific journal The Journal of Physiology. The findings reveal that ColdZyme targets the underlying cause of upper respiratory infections by inhibiting viruses' ability to infect cells and limiting their spread. Study participants who used the active product experienced significantly lower symptom rating scores and sick days due to colds.

The publication is a collaboration between researchers at the universities of Kent and Vienna. They examined ColdZyme's effects using complementary approaches: a randomized, double-blind, placebo-controlled study involving active athletes and a new in vitro model of the human upper respiratory tract.

The research team at Kent enrolled 164 active athletes who were randomized to use either ColdZyme or a placebo spray in their throat at the first signs of upper respiratory infection symptoms. Participants also submitted throat swabs for researchers to analyze the presence of viruses during symptom periods. The final results are based on 154 participants, as 10 of the 164 enrolled athletes were lost in follow-up. The results showed that athletes using the active product had significantly lower symptom score ratings and fewer lost training days due to colds compared to the placebo group (see figure below). Additionally, the findings demonstrated a significant reduction in viral load (94%) for rhinovirus—the most common cause of colds—when treated with ColdZyme, along with lower symptom scores.

-          This shows that ColdZyme addresses the underlying cause of upper respiratory infections by inhibiting viruses' ability to infect cells and limiting their spread. This results in less tissue damage in the airways and milder symptoms. The findings are very promising, and the reduced illness duration can be of practical benefit to both athletes and the general population, says Glen Davison, professor of Sport and Exercise Sciences in the School of Natural Sciences at the University of Kent, UK.

The in vitro study, conducted by the research team in Vienna, illustrated that ColdZyme effectively blocked cold viruses from adhering to the cell types present in the upper respiratory tract. Using human epithelial cells in models simulating different parts of the upper respiratory tract, such as the nose and throat, these models were infected with rhinovirus—the most common cause of colds. The researchers compared the effects of spraying the epithelial cells with either ColdZyme or a control (standard saline solution). When the cells were treated with ColdZyme, a significant reduction in viral load was observed.

-          These results are remarkable because ColdZyme not only significantly reduced the viral load for SARS-CoV-2 variants and Influenza A and B as previously demonstrated, but also for rhinoviruses in our upper respiratory tract model. After treatment with ColdZyme, previously infected tissue cultures appeared almost uninfected, with intact cell nuclei, undamaged cilia, and only a few remaining virus particles compared to infected cultures mock-treated with saline solution before infection says Doris Wilflingseder, professor of infectious diseases at the Ignaz Semmelweis Institute and the Vetmeduni Vienna.

 

-          Most people see colds as something you just have to endure. Therefore, we are very positive about the results from two independent, researcher-initiated studies, which in different ways show that ColdZyme addresses the root cause – the virus – rather than just alleviating the symptoms. The product shortens the duration of the illness and relieves discomfort, which we believe is valuable for everyone," says Claus Egstrand, CEO of Enzymatica.

 

The results from the studies:

ColdZyme – Viral load was 94% lower in ColdZyme group vs placebo (clinical study)

The results show the amount of rhinovirus in participants with a cold in the study (n = 50 confirmed cases of upper respiratory tract infection, URTI). Throat swabs were taken at several points during the first week of illness (day 1, 3, 5, and 7). The viral load was measured using PCR analysis, and the total viral burden over this 7-day period (7 days) was then calculated. The chart shows median values and the variation between participants. The results showed a significant difference between ColdZyme and placebo – the viral load was 94% lower in the ColdZyme group (P = 0.029). 

  

 

Amount of virus (in pink) lost in respiratory tissues when pre-treated with ColdZyme (in vitro study)

The images show how the amount of virus (pink color) was significantly reduced in airway cells treated with ColdZyme before being exposed to the virus. For each test, three independent samples were taken from different parts of the cell culture. The image shows an example of how the cells appeared in one of these samples.

 

 

ColdZyme – lower symptom ratings during infection compared to placebo (clinical study)

The graph shows how participants in the study rated their cold symptoms day by day. Each participant assessed eight different symptoms, which were then summed to a total score (Jackson score). The chart compares the average symptom levels of those who used ColdZyme with those who received placebo. The results show that those who used ColdZyme experienced milder symptoms during the infection.

 

ColdZyme – Fewer sick days during infection (clinical study)

The graph shows how many sick days participants in each group had during a cold period, based on 50 laboratory-confirmed cases in the study. It also shows how many of these days affected participants' training—either by forcing them to cancel their workouts entirely or by needing to train at a lower intensity than usual. The results indicate that those who used ColdZyme had fewer sick days and fewer training days affected compared to the placebo group.

Read the published article here: https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP288136