Hyperbolic tapering is increasingly recommended for the gradual reduction of psychiatric drugs to minimise withdrawal symptoms, yet available formulations rarely accommodate the small dose regimens required. To evaluate whether pharmaceutical manipulation strategies - as proposed in clinical guidelines for hyperbolic tapering - can produce progressively smaller haloperidol doses with adequate accuracy and precision. Strategies included whole and split tablets, liquid dispensed via dropper or dosing syringe, diluted solutions and tablet suspension, applied under controlled laboratory conditions. Haloperidol was used as a model, following an exponential 10% dose reduction schedule from 5 to 0 mg, generating multiple tapering steps that mirrored real-world scenarios. Drug content was quantified by high-performance liquid chromatography and interpreted according to an adapted pharmacopoeial criterion. All strategies yielded mean doses within 90-110% of expected values, demonstrating satisfactory accuracy and reproducibility. Variability was higher with tablet splitting, drop-based measurements and tablet suspension (relative standard deviation of 8.0%), whereas the use of whole tablets, dosing syringe and diluted liquid improved precision (relative standard deviation of 3.3%). These findings demonstrate the technical feasibility of achieving progressively smaller doses through standardised manipulation strategies, providing experimental support for hyperbolic tapering in clinical practice. Although off-label, such approaches currently offer the only practical means for safe dose reduction in the absence of smaller dose formulations, highlighting a regulatory gap between product design and clinical needs. Aligned with clinical guidelines, our findings support manipulation strategies as a practical and reliable component of individualised dose reduction in psychiatric care.

Hypoprolactinemia, an often overlooked condition in psychiatric practice, has been suggested to be associated with potential adverse effects on sexual and metabolic functions, similar to those reported in hyperprolactinemia. Recently, numerous studies have indicated that oral aripiprazole can lead to hypoprolactinemia in patients with various psychiatric disorders. However, the frequency and severity of hypoprolactinemia in bipolar patients receiving a 400-mg dose of once-monthly long-acting injectable aripiprazole remain unknown. This study aimed to assess the effects of once-monthly long-acting (400 mg) injectable aripiprazole on prolactin levels in patients with bipolar disorder. Fifty patients with bipolar disorder (25 women and 25 men) receiving the 400-mg dose of once-monthly long-acting injectable aripiprazole, either as monotherapy or in combination with other psychiatric medications, were recruited for this study. Overall, the rate of hypoprolactinemia was 52% among the study participants. When stratified by sex, the prevalence was 68% in men and 36% in women. In addition, 28% of male patients and 4% of female patients had serum prolactin levels below 1 ng/mL. Mean serum prolactin levels were significantly higher in women than in men (z=- 3.435, p=0.001). No significant correlation was observed between serum prolactin concentrations and age or treatment duration in either sex. Once-monthly injectable aripiprazole treatment in bipolar disorder was associated with a relatively high prevalence of hypoprolactinemia in both female and male patients. Given emerging evidence of potential metabolic and sexual effects of hypoprolactinemia, monitoring prolactin levels may be clinically relevant in patients receiving injectable aripiprazole.

Who receives psychiatry-focused pharmacogenomic testing, and is it associated with prescribing patterns and acute care utilisation in depression? Real-world evidence from a large health system.

RFK Jr takes aim at "overprescribing" of psychiatric drugs.

Introduction: Poisoning cases represent a major category of medical emergencies and remain an important cause of mortality, as well as leading contributor to acute diseases in many developing countries. The aim of this study was to investigate the frequency distribution of poisonings and provide appropriate strategies to reduce poisoning cases. Methods: This descriptive cross-sectional study was conducted on 609 poisoned patients who were referred to Shahid Beheshti Hospital in Taft, Yazd Province, Iran, during the year 2019. Sampling was performed using the census method. Data were collected using a researcher-made checklist by reviewing medical records and the Medical Care Monitoring System (MCMC). Statistical analyses were conducted using SPSS version 20. Descriptive statistics, - including frequency, percentage, mean, standard deviation-were calculated, and the chi-square test was used to compare qualitative variables. A p-value of less than 0.05 was considered statistically significant. Results: Out of 609 patients admitted to Shahid Beheshti Hospital in Taft, 49.6% were male and 50.4% were female. The average age of the participants was 27.49 (±14.64) years, with the highest percentage (39.9%) in the 19-30 age groups. The most common poisoning agent was drugs, accounting for 66.2%, of which 19.7% were psychiatric medications. The average hospital stay was 2.34 (±1.33) days. The highest and lowest rates of poisoning occurred in spring and summer, with 35.1% and 16.4%, respectively. Conclusion: The highest rate of intentional poisoning and suicide attempts was observed among young female individuals. As psychiatric drugs constitute the most common agents involved in drug-related poisonings, it is recommended that access to these medications be restricted and regulated, preventing their purchase without a physician’s prescription. Overall, given the number of hospitalization days due to poisoning and the high cost of treatment, measures should be taken to prevent poisoning cases.

Long-term study retention of adolescents undergoing metabolic and bariatric surgery: lessons learned from the Teen-Longitudinal Assessment of Bariatric Surgery cohort.

There is a growing literature on the concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with psychiatric disorders, and their safety and risks, in addition to potential therapeutic benefits in some disorders. The 2 cases presented in this issue report on potential adverse reactions from the combination of a GLP-1 RA and the patient's current psychiatric medication regimen. The first case involves a woman with bipolar disorder who developed lithium toxicity after being started on tirzepatide, which normalized after both medications were discontinued. The second case reports on a man with major depressive disorder who developed mood lability, irritability, and aggression after starting tirzepatide, which abated after the medication was stopped. These cases highlight the importance of monitoring all patients' medications to ensure that a GLP-1A RA does not affect the metabolism of medications through its potential gastrointestinal effects, while also evaluating any possible mood changes that may occur with this class of medications, despite growing evidence that they are not associated with worsening depression or suicidal thoughts. Further studies are needed to better understand the effects of GLP-1A RAs in patients with comorbid psychiatric disorders.

Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are among the most commonly used medications worldwide. It has been suggested that the misuse of such medications is not uncommon. The objective of the present research was to explore prevalence, reported reasons and psychopathological concomitants related to NSAIDs/paracetamol misuse in a sample of users. The sample was made of 346 NSAIDs or paracetamol users (age range: 18-64years); assessments included the 4-item Perceived Stress Scale (PSS-4), the 10-item version of the Adverse Childhood Experiences International Questionnaire (ACE-IQ-10), the Body Image Concern Inventory (BICI), the Alcohol Use Disorders Identification Test-C (AUDIT-C), and questions related to NSAIDs/paracetamol misuse. Forty-eight individuals (13.9%) were categorized as NSAIDs/paracetamol misusers. A logistic regression model showed that higher scores in AUDIT-C, BICI and ACE-IQ-10, and the use of psychiatric medications, were significantly associated with the likelihood of NSAIDs/paracetamol misuse. Specific reasons related to the misuse are also reported. Our findings provide novel insights into the relationship between NSAIDs/paracetamol misuse and psychopathology, with potential clinical implications for prevention and treatment.

Postdiagnostic anxiety and depression's impact on management and outcomes in patients with unruptured intracranial aneurysms remains underexplored. We assessed associations with treatment patterns and outcomes using a large multi-institutional database. This retrospective cohort study used TriNetX Global Collaborative Network records (2015-2025; >130 million patients across ≈250 health care organizations), identifying 127 361 adults with unruptured intracranial aneurysms. Addressing immortal time bias, we used a 127-day landmark analysis (median time to psychiatric diagnosis), requiring event-free survival before cohort assignment. Of 119 211 patients surviving to the landmark, those with anxiety/depression diagnosed within 0 to 127 days (n=7250) were 1:1 propensity score matched to controls (n=111 961), yielding 6800 per cohort. Cox proportional hazards models evaluated outcomes from a landmark. Matched cohorts (6800 each) had balanced characteristics (all standardized mean differences <0.10) and comparable follow-up (median, 1550 versus 1600 days). Anxiety/depression was associated with higher all-cause mortality (6.3% versus 4.5%; hazard ratio [HR], 1.28 [95% CI, 1.11-1.48]; P<0.001) and rupture (3.1% versus 2.2%; HR, 1.33 [95% CI, 1.08-1.64]; P=0.007). Five-year survival was 93.7% in the anxiety/depression cohort versus 95.5% in matched controls. Preventive treatment showed nonsignificant trends toward lower rates (odds ratio, 0.80 [95% CI, 0.62-1.03]; P=0.082). Sensitivity analysis using a 365-day landmark (n=10 200 per cohort) expanded eligibility by including diagnoses between days 128 and 365, and confirmed findings (mortality HR, 1.22 [95% CI, 1.08-1.38]; rupture HR, 1.28 [95% CI, 1.08-1.52]). Fine-Gray competing risk models yielded consistent results (mortality subdistribution HR, 1.27; rupture subdistribution HR, 1.31). Dose-response patterns emerged for psychiatric medication adherence: low (mortality HR, 1.50 [95% CI, 1.12-2.00]; P=0.006), moderate (HR, 1.29 [95% CI, 0.98-1.70]; P=0.071), and high (HR, 1.16 [95% CI, 0.89-1.51]; P=0.270). E values were 1.88 for mortality and 1.99 for rupture. Postdiagnostic anxiety and depression are associated with increased rupture risk and mortality in patients with unruptured intracranial aneurysms. Residual confounding cannot be excluded. These findings require further investigation to establish causality and suggest that an integrated psychiatric assessment may be considered in unruptured intracranial aneurysm management.

Mild Behavioral Impairment (MBI) reflects later-life emergence of persistent neuropsychiatric symptoms and is increasingly recognized as an early manifestation of neurodegenerative disease, yet cerebellar correlates remain underexplored. We tested whether cerebellar morphometry is associated with incident MBI in mild cognitive impairment (MCI). Using longitudinal Alzheimer's Disease Neuroimaging Initiative data, MBI was derived from Neuropsychiatric Inventory/ Neuropsychiatric Inventory-Questionnaire items mapped to five diagnostic domains and defined as new symptoms persisting for ≥2 consecutive visits after a symptom-free baseline. Of 530 MCI participants without baseline symptoms, 181 who developed MBI were matched 1:1 to controls by age, sex, and education. DeepCERES quantified lobular cerebellar cortical thickness and asymmetry from 3T T1-weighted MRI. We used logistic regression with false discovery rate correction and conducted domain-specific analyses (affective dysregulation, impulse dyscontrol, decreased motivation). MBI cases had lower Mini Mental State Examination scores and higher dementia conversion than controls. Greater thickness in right cerebellar lobules IV (OR 1.215), V (OR 1.122), and VIIIB (OR 1.169), and greater asymmetry in right lobule V (OR 1.035), were associated with incident MBI. Affective dysregulation showed the strongest, largely right-lateralized associations and greater interhemispheric asymmetry. Main results were unchanged after separate sensitivity adjustments for Mini Mental State Examination scores and for index-visit psychiatric medication use. Incident MBI in MCI is linked to right-lateralized cerebellar cortical thickening and asymmetry, most prominently for affective dysregulation. These patterns may reflect early compensatory and/or neuroinflammatory processes within cerebello-cortical circuits relevant to affect regulation.

Pharmacy of the Mind: The Uncanny Origins of Psychiatric Drugs, and The World That Shaped Them.

Individuals with schizophrenia or bipolar disorder face a significantly elevated risk of obesity, primarily due to weight gain associated with psychiatric medications and lifestyle factors. While digital self-monitoring tools offer scalable solutions, their application remains underexplored in psychiatric populations. To address these gaps, this type 1 hybrid effectiveness-implementation study investigates the preliminary effectiveness and implementation feasibility of a mobile health-assisted weight management intervention for patients with severe mental illness. This study aims to evaluate the preliminary effectiveness and implementation feasibility of a mobile health-assisted weight management intervention for patients with severe mental illness transitioning from inpatient care to community-based recovery. This single-center, open-cohort stepped-wedge cluster randomized trial with a 2-month step duration will recruit 204 patients from 6 clinical units. Clusters are randomized into 2 waves, with staggered transitions to a digital intervention, including smart scales, health apps, and biweekly educational modules, over a 6-month observation period. The design evaluates the intervention across the transition from inpatient care to community-based recovery. The primary outcome is the proportion of participants achieving ≥5% weight loss at month 6. Implementation feasibility is assessed through device technical success and intervention adherence (defined as ≥50% completion of weekly weigh-ins and daily dietary logs). Participant data collection began in May 2023 and was completed by June 2025 with a total of 204 participants. The publication of key findings and results is anticipated in late 2026. This protocol describes a pragmatic, technology-supported intervention designed to address metabolic side effects in a tertiary psychiatric setting. By bridging the gap between acute hospitalization and community recovery, this hybrid stepped-wedge cluster randomized trial provides a crucial framework for integrating digital metabolic monitoring into routine clinical workflows for vulnerable populations.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition often associated with communication barriers, sensory sensitivities, and behavioral challenges, including agitation. Identifying the underlying causes of acute agitation in nonverbal individuals with ASD can be difficult, leading to diagnostic delays and unnecessary medical interventions. We present a case of a 36-year-old nonverbal male with ASD who was admitted for severe agitation, self-injurious behaviors, and increased aggression towards family members. His medical history included epilepsy, hypertension, and prior otitis media with tympanostomy tubes. Initial evaluations, including CT imaging and laboratory tests, were unremarkable. Despite escalation of psychiatric medications, including haloperidol and ziprasidone, along with dexmedetomidine infusion and physical restraints, his agitation persisted. Given his history of ear infections, further examination revealed cerumen impaction in his right ear. Following ear lavage, the patient's behavior significantly improved, agitation resolved, and he was safely discharged home. This case underscores the importance of a thorough diagnostic approach when evaluating agitation in individuals with ASD, particularly those with communication limitations. Sensory disturbances, such as cerumen impaction, may be overlooked contributors to distress. Additionally, maintaining a familiar environment and involving caregivers played a crucial role in the patient's stabilization. While pharmacologic and physical interventions were initially necessary for patient and provider safety, restraints may have exacerbated distress. This highlights the need for alternative strategies, including early sensory evaluations, behavioral interventions, and specialized ASD-friendly healthcare protocols. Agitation in ASD patients requires a multidisciplinary approach that considers sensory, medical, and environmental factors. Healthcare providers should remain vigilant for treatable conditions like cerumen impaction and prioritize nonpharmacologic interventions to minimize distress and improve patient outcomes. Incorporating a sensory-first bedside check, including an ear exam, can prevent unnecessary escalation and reduce restraint exposure.

Association of psychiatric drugs with cardiovascular symptoms in medical university students

Contemporary psychiatric research operates within a publication ecosystem marked by structural asymmetries of power, increasing entanglements with pharmaceutical interests, and limited tolerance for sustained methodological critique. In such contexts, critical perspectives that challenge biologically reductionist interpretations or foreground the adverse effects of widely prescribed medications may face implicit barriers, even when their arguments are scientifically sound. A recent case–control study by Magen et al. (2025) reported associations between acute urticaria and psychiatric disorders, primarily personality and anxiety disorders. While the authors speculated about biological pathways, they did not test or adequately discuss the role of psychiatric medications, despite having access to prescription data and despite urticaria being a well-documented adverse effect of several psychotropic drugs, including those commonly prescribed for anxiety. These validity concerns are compounded by the editorial handling of a letter to the editor we submitted in response. Although the critique was explicitly acknowledged as “valid,” it was rejected on the grounds that similar concerns had been raised in our previous commentaries on related studies by the same research group. Such reasoning shifts the focus away from the strength of the arguments toward the identity and persistence of the critics, effectively muting legitimate scrutiny while allowing methodological flaws to recur unchallenged. Together, these two issues—the systematic neglect of medication effects and the suppression of critical debate—threaten not only scientific progress but also public trust in mental health research, particularly in the presence of undisclosed conflicts of interest. More broadly, this case highlights the risk that the pursuit of biological explanations, when not accompanied by transparency and methodological rigor, may reinforce a narrow form of reductionism that obscures the complex reality of mind–body relations and encourages the overuse of potentially harmful medications.

Patients who have been exposed to psychological trauma during their lifetime, regardless of the severity of the trauma, are more likely to experience depression and anxiety. However, there are limited data on the prevalence of depression and anxiety disorders among females after exposure to trauma in Jordan. This is a cross-sectional study using an online survey that was conducted between the start of April 2025 and the end of June 2025. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 questionnaires were used to evaluate depression and anxiety after exposure to psychological trauma. A total of 1025 females participated in this study. The most reported type of trauma was death or loss of a loved one (38.6%), followed by betrayal trauma (27.1%) and sexual or physical assault (12.0% and 11.9%, respectively). Most participants had experienced trauma for 1 to 3 years (33.0%). Despite high levels of reported trauma, only a small fraction sought psychological help; 62 respondents (6.0%) sought psychological help for anxiety, and 59 (5.8%) for depression. Psychiatric medication was used by 183 participants (18.5%), but 113 (61.7%) of them reported no improvement. The majority (68.3%) stopped their medication mainly due to side effects (56.8%) and high costs (40.8%). In addition, higher education levels, such as holding a bachelor's degree, were associated with lower odds of anxiety (adjusted odds ratio = 0.4, 95% confidence interval: 0.3-0.7, P < .001) and depression (adjusted odds ratio = 0.6, 95% confidence interval: 0.4-1.0, P = .038). This study suggests that factors affecting depression are often unresolved grief or loss, a history of trauma, and chronic stress. Furthermore, people suffering from trauma and emotional and social problems are more likely to develop anxiety and depression than others. Also, a few people with depression or anxiety see psychiatrists. Patients who used psychiatric medications reported no improvement and discontinued their treatment due to side effects and the high cost of the medication. Moreover, people with higher levels of education are less likely to develop anxiety.

Systemic and ophthalmic drugs associated with glaucoma: an international, population-based observational study.

This study aims to identify readily available admission variables associated with unintentional medicinal discrepancies (UMDs) in psychiatric settings and to develop a feasible prioritisation rule with robust psychometric performance. This observational study collected information on items available at admission for patients admitted to six French psychiatric hospitals between June and August 2021. Based on the international literature and personal experience feedback, a multidisciplinary committee network and a psychiatry-mental health research federation elaborated a list of items potentially valuable for prioritisation and proposed a specific tool for psychiatric settings, named O-PsyConcil. Medication reconciliation (MR) was performed, and UMDs were identified. Items associated with UMDs were investigated through a backward stepwise logistic regression model, calculating adjusted ORs and their 95% CIs. The prioritisation rules were proposed using the more efficient combination in terms of feasibility and psychometric characteristics. The study included 513 patients (median age 48 years, IQR 33-68; 48% women). Factors associated with UMDs were comorbidities (OR 1.49 for one more comorbidity; 95% CI 1.23 to 1.82), psychiatric high-risk medications (HRMs) (2.64; 1.68 to 4.16), and somatic HRMs (3.43; 1.70 to 7.06). Based on these results, the prioritisation rule combining one comorbidity and/or one psychotropic HRM and/or one somatic HRM led to assessing 61% of the total population, with median performances of 82% (IQR 78-85%) for sensitivity and 48% (43-52%) for specificity. The O-PsyConcil tool demonstrated satisfactory performance, suggesting it could enhance the efficiency of psychiatric MR compared with standard non-prioritised MR.

Abstract Introduction Gradual dosage reduction (tapering) is the recommended approach for reducing and/or stopping the use of psychiatric medication in order to minimise the risk of withdrawal symptoms. A previous James Lind Alliance Priority Setting Partnership highlighted several gaps in the current evidence base on tapering psychiatric medication.[1] To date, the evidence base for mobile phone applications (‘apps’) and app-based interventions in supporting safe and effective discontinuation of psychiatric medications has not been examined. Aim To examine the content, underpinning evidence base, and impact of mobile phone apps and app-based interventions that focused on supporting the tapering of psychiatric medication. Methods A scoping review was conducted using the Joanna Briggs Institute guidance and results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guideline.[2] Seven electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, ACM, IEEE Xplore) and two app stores (Apple’s App Store (iOS) and Google Play Store (Android)) were searched. To meet inclusion criteria, studies of any design identified from peer-reviewed literature (i.e. ‘non-commercial’ apps) and apps identified from searches of commercial app stores (i.e. ‘commercial’ apps) had to focus on supporting the tapering of psychiatric medication. Following screening, key information was extracted from included studies and apps. Identified apps were coded in terms of their functionalities and components of the Behaviour Change Technique Taxonomy version 1 (BCTTv1). The findings were described using narrative synthesis. Results Seven apps met inclusion criteria comprising two non-commercial apps, and five commercial apps. Two non-commercial apps were evaluated using randomised controlled trials (RCTs); one RCT was ongoing and the other was stopped prematurely due to recruitment challenges. All seven apps focused on supporting the tapering of psychiatric medication. Eight functionalities and seventeen BCTs were identified across the seven included apps and app companion websites. The four most common BCT codes were: 1.3 ‘Goal setting (outcome), 2.3 ‘Self-monitoring of behaviour,’ 4.1 ‘Instructions on how to perform the behaviour,’ and 8.7 ‘Graded tasks.’ Most of the identified apps did not provide information about the app development process or specify any theoretical underpinning. Given the lack of reported outcomes for the evaluation studies of app-based interventions and commercial apps, it was not possible to report the impact from a qualitative or quantitative perspective. Conclusion This scoping review demonstrated a paucity of mobile phone apps and studies of app-based interventions that support tapering psychiatric medication. The review’s main strength was that it followed a published protocol, and data extraction and app coding was conducted by two reviewers independently. In terms of limitations, the lack of studies evaluating app-based interventions made it difficult to address the objective relating to the impact of the identified apps. By outlining the key functionalities offered by the identified apps and characterising them in terms of component BCTs, as well as raising awareness of the shortcomings of commercially available apps, the review findings will guide future research on the development and evaluation of apps to support individuals who want to reduce or stop psychiatric medication use.

For the past half-century, psychiatric drug development has largely focused on tweaking neurotransmitter receptors and chemical pathways. Yet despite billions of dollars invested and major advances in neuroscience, truly innovative treatments for mental illness remain scarce. Disorders like depression, schizophrenia, and post-traumatic stress disorder (PTSD) continue to be managed with drugs discovered decades ago that often provide only partial relief, with remission rates of approximately 30-40% for treatment-resistant depression and 60-70% of schizophrenia patients experiencing persistent symptoms despite medication. This stagnation has prompted a paradigm shift - what if the key to treating mental illness is not just which receptor a drug targets, but how it changes the brain's processing of sensory information? In this treatise, I propose that many psychiatric conditions stem from breakdowns in the brain's sensory filtering mechanisms, the neural circuits that gate irrelevant stimuli before they consume valuable processing resources, and that effective therapies must restore these filtering functions. While computational psychiatry has long recognized that mental illness may reflect failures in predictive filtering, the specific neural substrate implementing this gating remains underspecified. Here the cerebellum emerges as a critical hub: neuroanatomically positioned to perform bottom-up sensory gating before cortical processing, housing more than half the brain's neurons in an architecture ideally suited for distilling signal from noise and showing state-dependent disruption of cerebellar-cortical connectivity during symptom provocation in PTSD. Intriguingly, psychedelic drugs may act as recalibration triggers for these neural filters, acutely disrupting entrenched filtering architectures and reopening windows of plasticity through which maladaptive sensory weightings can be reset. This cerebellar filtering framework offers a neuroanatomically specified extension of predictive processing theory, generates falsifiable predictions, and suggests novel therapeutic targets for conditions that have resisted a half-century of receptor-focused drug development.