Radically different
Background: Ambulatory assessment and active and passive monitoring all offer a real-time, flexible approach to assessing mood and behavior in mood disorders. Despite their potential, concerns remain regarding the performance, usability, adherence, and potential safety of these tools. Objective: This study synthesizes the findings from 7 systematic reviews, integrating quantitative and qualitative data from randomized trials, observational studies, and user experience research to evaluate the performance, feasibility, acceptability, and clinical impact of ambulatory assessment and mood monitoring in people with depression and bipolar disorder. We assessed studies over the medium or long term (3 months or more). Methods: A summary of a series of systematic reviews was carried out by the authors—including meta-analyses (for quantitative data) and meta-syntheses (for qualitative data). Eight electronic databases were searched, and mixed methods studies were included. Studies were assessed for risk of bias. The results were checked for coherence, and recommendations were made by individuals with lived experience, methodologists, and psychiatrists. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality and strength of the evidence. Results: The 111 included studies included 19,945 participants and used 69 different ambulatory assessment protocols or mood-monitoring interventions. Key barriers to implementation were identified, including performance inconsistency, adverse effects, and user disengagement. Evidence-based recommendations are provided to guide future clinical and research applications. Conclusions: Ambulatory assessment and mood monitoring hold promise in research and clinical practice, yet their implementation requires more rigorous evaluation, greater personalization, and responsible, user-centered design. Crucially, these measures can add granularity and confirmation, but additional context is often required, and none of these measures are robust enough yet to replace current outcomes.
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Background: There is a need for scalable and simple interventions for trauma-exposed people. In this case series, we built on our previous case study and case series findings and further explored the use and potential effectiveness of a brief novel intervention to reduce the number of past intrusive memories of trauma. The imagery competing task intervention consists of a memory reminder and the visuospatial task Tetris played with mental rotation, targeting 1 intrusive memory at a time. Here, we test remote delivery of the intervention, including guidance from researchers without specialist mental health training, in a sample of women in Iceland with current intrusive memories from trauma. Objective: In a case series of trauma-exposed women, we aimed to explore whether this brief novel intervention reduces the number of established intrusive memories (primary outcome) and improves general functioning and symptom reduction in posttraumatic stress, depression, and anxiety (secondary outcomes). The acceptability of the intervention along with adaptations, that is, delivery by psychology students without specialist mental health training and digital delivery, was explored. Methods: Participants (N=8) monitored the number of intrusive memories from an index trauma (occurring 3‐16 years previously) in a daily diary at baseline, during the intervention, and postintervention at 1-month and 3-month follow-ups. The intervention was delivered digitally with guidance from clinical psychologists or psychology students. A repeated AB design was used (“A”: preintervention baseline, “B”: intervention phase). Intrusions were targeted one by one, creating repetitions of an AB design (ie, length of baseline “A” and intervention “B” varied for each memory). Results: The number of intrusive memories reduced for all participants from the baseline phase compared with the intervention phase, although the reduction was minimal for 2 participants (6.3%‐93%). The number of intrusive memories continued to reduce for 6 out of 8 participants (58%‐100% reduction at 1-month follow-up; 72%‐100% reduction at 3-month follow-up). Symptoms of posttraumatic stress, depression, and anxiety were reduced for most participants postintervention and continued to decrease during the follow-up periods. Functioning was improved for 7 of the 8 participants from baseline to postintervention and continued to improve at the follow-up assessments for 3 participants. The intervention delivered digitally and partly by students was perceived to be an acceptable way to reduce the frequency of intrusive memories by all participants (mean rating 9.5 out of 10). Conclusions: Data from this case series of traumatized women provide preliminary evidence for the effectiveness of this novel brief intervention in reducing intrusive memories of trauma occurring several years ago and in improving functioning and reducing core symptom burden. This study will inform a randomized controlled trial of this novel intervention, which may have considerable implications for large-scale clinical management of traumatized populations. Trial Registration: ClinicalTrials.gov NCT04209283; https://clinicaltrials.gov/study/NCT04209283 International Registered Report Identifier (IRRID): RR2-10.2196/29873
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Researchers in Sweden report that a single dose of psilocybin, a psychedelic compound found in mushrooms, can provide rapid relief from depressive symptoms. Results from a small-scale Phase II trial, published today in JAMA Network Open, show that patients experienced an improvement as soon as two days after treatment, with effects persisting for longer than three months.
”Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” says Hampus Yngwe, MD, consultant psychiatrist and PhD student at the department of clinical neuroscience of the Karolinska Institutet in Stockholm.
Major depressive disorder is commonly treated with selective serotonin reuptake inhibitors (SSRIs), but most patients do not respond to this treatment or become resistant. In addition, their effects can typically take several weeks to be noticeable, and side effects are common.
Previous research had shown that a single dose of psilocybin can have antidepressant effects in people with treatment-resistant depression or anxiety disorders in patients with advanced cancer. The current study looked instead at the effects of this compound on “common” forms of major depressive disorder.
The study recruited a total of 35 people with moderate to severe recurrent depression, between 20 and 65 years of age. They were randomly assigned to receive either a single 25mg dose of psilocybin or niacin, an active placebo that causes a noticeable physical reaction. All patients received psychotherapeutic support before, during, and after treatment.
Participants were evaluated using the Montgomery–Åsberg depression rating scale (MADRS) to assess treatment effects at multiple time points after dosing. After a week, the group who received psilocybin saw an average MADRS score reduction of 9.7 points, compared to 2.4 points in the placebo group, and these effects persisted after two weeks and six weeks. At this point, 53% of participants who received psilocybin were in remission, compared to 6% in the placebo group.
A self-reported version of the MADRS revealed that patients saw antidepressant effects as early as day two after dosing, and continued to experience these positive effects for over three months.
A year after treatment, all patients who received psilocybin treatment remained in remission. However, many of the patients who received the placebo had also recovered at that point, showing no major statistical difference between both groups.
“The long-term effects are uncertain,” says Yngwe. “Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”
Because the effects of psilocybin are strong and easily recognizable, many participants were able to tell whether they had received the treatment or the placebo. This is a common challenge scientists face when studying psychedelic treatments that can make it difficult for patients and researchers alike to separate the effects of the treatment from their expectations. “We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” notes Yngwe.
Next, the researchers will analyze data from PET scans, blood, and cerebrospinal fluid samples collected from all patients before and after dosing. This will help them understand the physiological changes induced by psilocybin, and how these influence its observed antidepressant effects.
”Research suggests that the interaction between parts of the brain is impaired in depression and that this may be linked to changes in the connections between nerve cells, known as synapses,” says Yngwe. “In preclinical studies, psychedelics have been shown to stimulate synaptic growth. We therefore want to investigate whether psilocybin alters synaptic density in the brain.”
The post Single Psilocybin Dose Relieves Depression for Over Three Months appeared first on Inside Precision Medicine.
Background: Large language models (LLMs) are poised to transform mental health care, offering advanced capabilities in diagnosis, prognosis, and decision support. Since their inception, numerous mental health-focused LLMs have emerged in the scientific literature, reflecting the growing interest in leveraging these models across various clinical applications. With a broad range of models available, diverse optimization strategies, and multiple use cases, reviewing the current landscape is critical to understanding where future impact lies. Objective: This study aimed to conduct a scoping review investigating the use of LLMs in mental health across diagnostic, prognostic, and decision support tasks. Methods: We screened 3121 papers from PubMed, Scopus, and Web of Science for studies published between January 2023 and October 2025, using terms related to LLM and mental health. After removing duplicates, 2 reviewers (MCL and WWBG) independently screened the studies, with a third (JJK) to resolve conflicting opinions. We extracted and synthesized information on the models, use cases, datasets, and adaptation methods from selected papers. Results: In total, 41 papers were selected. Many studies included evaluations on OpenAI’s GPT series applications: GPT-4 (24 studies, 58.5%) and GPT-3.5 (16 studies, 39%). Others included Bidirectional Encoder Representations from Transformers-derived models (9 studies, 22%), LLaMA (8 studies, 19.5%), and RoBERTa-derived models (6 studies, 14.6%). While all studies initially applied out-of-the-box LLMs, several adapted them through few-shot learning or fine-tuning to better align with specific research goals. The most common use case was in diagnostics (31 studies, 75.6%), while the most common target condition was depression (11 studies, 26.8%). While many studies reported superior performance of LLMs, only a minority of studies (13 studies, 31.7%) validated LLM performance against clinician assessments using real patient data, with the majority relying on proxy outcomes such as clinical vignettes, examination questions, or social media posts. Conclusions: Despite rapid growth and diversity of LLM applications in mental health, the field remains nascent and exploratory. Future developments must emphasize consistent model adaptation procedures to ensure safety and clinical workflow alignment. Models must also be evaluated on robust evaluation criteria by using standardized protocols and real clinical outcome measures.
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