Erkan Kuru, Ilker Ozdemir, Bengu Yucens, M. Hakan Türkçapar
Background
The paliperidone palmitate 3-month (PP3M) formulation offers an extended dosing interval compared to the 1-month (PP1M) formulation. However, data on the comparative side effect profiles of PP1M versus PP3M in real-world settings remain limited. This study aimed to compare the side effect profiles in patients with schizophrenia receiving PP1M and those who switched from PP1M to PP3M.
Material and Methods
Of 473 patients with schizophrenia screened, 132 received long-acting injectable antipsychotics; 67 initiated PP1M, of whom 43 subsequently converted to PP3M and had evaluable data at both time points. The primary analysis used a within-patient mirror-image design (PP1M month-4 vs PP3M month-4). Side effects were assessed using the UKU Side Effect Rating Scale, and symptom severity was evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms, at 4 months after PP1M initiation and 4 months after PP3M switch.
Results
UKU side-effect profiles were broadly similar after conversion to PP3M, with no increase in the UKU total score. The most frequent side effects for both formulations were increased fatigability, hypokinesia, weight gain, and diminished sexual desire. The frequency of side effects remained mostly stable, with constipation showing a significant decrease after switching. Side effects were more prevalent in patients with schizophrenia using multiple antipsychotics compared to monotherapy.
Conclusion
In this within-patient cohort stabilized on PP1M, conversion to PP3M was not associated with an increase in overall UKU side-effect burden. Selecting the appropriate dose before switching and preferring monotherapy may enhance treatment comfort. These results may help guide clinicians in selecting long-acting injectable antipsychotics in practice.
{"title":"Comparison of Side Effects Between 3-Monthly and 1-Monthly Paliperidone Palmitate Formulations in Patients With Schizophrenia","authors":"Erkan Kuru, Ilker Ozdemir, Bengu Yucens, M. Hakan Türkçapar","doi":"10.1002/hup.70033","DOIUrl":"10.1002/hup.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The paliperidone palmitate 3-month (PP3M) formulation offers an extended dosing interval compared to the 1-month (PP1M) formulation. However, data on the comparative side effect profiles of PP1M versus PP3M in real-world settings remain limited. This study aimed to compare the side effect profiles in patients with schizophrenia receiving PP1M and those who switched from PP1M to PP3M.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>Of 473 patients with schizophrenia screened, 132 received long-acting injectable antipsychotics; 67 initiated PP1M, of whom 43 subsequently converted to PP3M and had evaluable data at both time points. The primary analysis used a within-patient mirror-image design (PP1M month-4 vs PP3M month-4). Side effects were assessed using the UKU Side Effect Rating Scale, and symptom severity was evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms, at 4 months after PP1M initiation and 4 months after PP3M switch.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UKU side-effect profiles were broadly similar after conversion to PP3M, with no increase in the UKU total score. The most frequent side effects for both formulations were increased fatigability, hypokinesia, weight gain, and diminished sexual desire. The frequency of side effects remained mostly stable, with constipation showing a significant decrease after switching. Side effects were more prevalent in patients with schizophrenia using multiple antipsychotics compared to monotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this within-patient cohort stabilized on PP1M, conversion to PP3M was not associated with an increase in overall UKU side-effect burden. Selecting the appropriate dose before switching and preferring monotherapy may enhance treatment comfort. These results may help guide clinicians in selecting long-acting injectable antipsychotics in practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brunno Freitas da Costa, Paula Hartmann, Daniel Pagnin
Objective
Anxiety is common in patients receiving end-of-life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficacy and safety of pharmacological treatments for anxiety in end-of-life care.
Design
Systematic review following PRISMA guidelines, prospectively registered in PROSPERO (CRD42024556913). Comprehensive searches were performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Eligible studies included adults receiving end-of-life care and evaluated pharmacological interventions targeting anxiety.
Results
Five studies met inclusion criteria: two assessing benzodiazepines combined with opioids and three evaluating psilocybin. Both benzodiazepine-opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin studies reported rapid and sustained anxiety relief, with approximately 60%–80% of participants experiencing clinically significant improvements. Both treatment categories showed good tolerability without serious adverse events. However, the evidence base was limited by small sample sizes and narrow study contexts.
Conclusions
Benzodiazepine-opioid combinations and psilocybin show promise for anxiety relief in end-of-life patients. Nevertheless, limited high-quality evidence highlights an important research gap. Further robust clinical trials are needed to confirm these findings and guide clinical practice in palliative care.
{"title":"Pharmacological Management of Anxiety in End-of-Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin","authors":"Brunno Freitas da Costa, Paula Hartmann, Daniel Pagnin","doi":"10.1002/hup.70032","DOIUrl":"10.1002/hup.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Anxiety is common in patients receiving end-of-life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficacy and safety of pharmacological treatments for anxiety in end-of-life care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Systematic review following PRISMA guidelines, prospectively registered in PROSPERO (CRD42024556913). Comprehensive searches were performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Eligible studies included adults receiving end-of-life care and evaluated pharmacological interventions targeting anxiety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five studies met inclusion criteria: two assessing benzodiazepines combined with opioids and three evaluating psilocybin. Both benzodiazepine-opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin studies reported rapid and sustained anxiety relief, with approximately 60%–80% of participants experiencing clinically significant improvements. Both treatment categories showed good tolerability without serious adverse events. However, the evidence base was limited by small sample sizes and narrow study contexts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Benzodiazepine-opioid combinations and psilocybin show promise for anxiety relief in end-of-life patients. Nevertheless, limited high-quality evidence highlights an important research gap. Further robust clinical trials are needed to confirm these findings and guide clinical practice in palliative care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan J. Stein, Alan E. Kazdin, David S. Baldwin, Meredith G. Harris, Irving Hwang, Julia R. Pozuelo, Nancy A. Sampson, Peter Woodruff, Maria Carmen Viana, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Jordi Alonso, Laura Helena Andrade, Corina Benjet, Ronny Bruffaerts, José-Miguel Caldas-de-Almeida, Stephanie Chardoul, Giovanni de Girolamo, Oye Gureje, Josep M. Haro, Elie G. Karam, Aimee Karam, Viviane Kovess-Masfety, Fernando Navarro-Mateu, Daisuke Nishi, José Posada-Villa, Annelieke Roest, Juan Carlos Stagnaro, Cristian Vladescu, Daniel V. Vigo, Ronald C. Kessler, the WHO World Mental Health Survey collaborators
<div> <section> <h3> Background</h3> <p>Anxiolytic medications, particularly benzodiazepines, are widely prescribed, giving impetus to long-standing debates about how often these agents should be employed in clinical practice. There are, however, few cross-country studies of the pharmacoepidemiology of these agents. We report on the frequency of anxiolytic medication use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.</p> </section> <section> <h3> Methods</h3> <p>Face-to-face interviews with community samples totaling <i>n</i> = 49,919 respondents in the World Health Organization World Mental Health (WMH) Surveys asked about anxiolytic medication use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses to all respondents.</p> </section> <section> <h3> Results</h3> <p>A weighted 5.6% (<i>n</i> = 4079) of respondents reported anxiolytic medication use within the past 12 months; the vast majority comprised benzodiazepine use, and use was highest amongst respondents with a subthreshold major depressive episode (MDE) (25.2%) and a 12-month MDE (19.8%). Rates were significantly higher in high-income countries (HICs) than low- and middle-income countries (LMICs) (8.5% vs. 2.2%, χ<sup>2</sup><sub>1</sub> = 559.6, <i>p</i> < 0.001). Short-acting benzodiazepines and z-drugs were most commonly used for sleep (66.5% and 85.5%), while intermediate-acting benzodiazepines and long-acting benzodiazepines were most commonly used either for sleep (37.9% and 30.1%) or anxiety (33.3% and 32.0%). Across all conditions, anxiolytic medications were reported as <i>very</i> effective by 55.7% of users and <i>somewhat</i> effective by an additional 32.2% of users, with similar proportions in HICs and LMICs. Negative predictors of high perceived effectiveness were a 12-month MDE and taking anxiolytic medication for comorbid anxiety and depression.</p> </section> <section> <h3> Conclusion</h3> <p>These data do not definitely answer the question of how often benzodiazepines should be prescribed in clinical practice, but they usefully inform discussions of how to optimize their use. It is noteworthy that anxiolytic medications, particularly benzodiazepines, are largely prescribed for anxiety and sleep, and that they are widely perceived to be either very or somewhat effective by users. However, more targeted prescription of these agents may be necessary; in particular antidepressant intervention should be pri
{"title":"Anxiolytic Medication Use in Low- Middle- and High-Income Countries: A World Mental Health Surveys Report","authors":"Dan J. Stein, Alan E. Kazdin, David S. Baldwin, Meredith G. Harris, Irving Hwang, Julia R. Pozuelo, Nancy A. Sampson, Peter Woodruff, Maria Carmen Viana, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Jordi Alonso, Laura Helena Andrade, Corina Benjet, Ronny Bruffaerts, José-Miguel Caldas-de-Almeida, Stephanie Chardoul, Giovanni de Girolamo, Oye Gureje, Josep M. Haro, Elie G. Karam, Aimee Karam, Viviane Kovess-Masfety, Fernando Navarro-Mateu, Daisuke Nishi, José Posada-Villa, Annelieke Roest, Juan Carlos Stagnaro, Cristian Vladescu, Daniel V. Vigo, Ronald C. Kessler, the WHO World Mental Health Survey collaborators","doi":"10.1002/hup.70031","DOIUrl":"10.1002/hup.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anxiolytic medications, particularly benzodiazepines, are widely prescribed, giving impetus to long-standing debates about how often these agents should be employed in clinical practice. There are, however, few cross-country studies of the pharmacoepidemiology of these agents. We report on the frequency of anxiolytic medication use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Face-to-face interviews with community samples totaling <i>n</i> = 49,919 respondents in the World Health Organization World Mental Health (WMH) Surveys asked about anxiolytic medication use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses to all respondents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A weighted 5.6% (<i>n</i> = 4079) of respondents reported anxiolytic medication use within the past 12 months; the vast majority comprised benzodiazepine use, and use was highest amongst respondents with a subthreshold major depressive episode (MDE) (25.2%) and a 12-month MDE (19.8%). Rates were significantly higher in high-income countries (HICs) than low- and middle-income countries (LMICs) (8.5% vs. 2.2%, χ<sup>2</sup><sub>1</sub> = 559.6, <i>p</i> < 0.001). Short-acting benzodiazepines and z-drugs were most commonly used for sleep (66.5% and 85.5%), while intermediate-acting benzodiazepines and long-acting benzodiazepines were most commonly used either for sleep (37.9% and 30.1%) or anxiety (33.3% and 32.0%). Across all conditions, anxiolytic medications were reported as <i>very</i> effective by 55.7% of users and <i>somewhat</i> effective by an additional 32.2% of users, with similar proportions in HICs and LMICs. Negative predictors of high perceived effectiveness were a 12-month MDE and taking anxiolytic medication for comorbid anxiety and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data do not definitely answer the question of how often benzodiazepines should be prescribed in clinical practice, but they usefully inform discussions of how to optimize their use. It is noteworthy that anxiolytic medications, particularly benzodiazepines, are largely prescribed for anxiety and sleep, and that they are widely perceived to be either very or somewhat effective by users. However, more targeted prescription of these agents may be necessary; in particular antidepressant intervention should be pri","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145867110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive.
{"title":"Aroma of Genius Essential Oil Blend Significantly Enhances Cognitive Performance and Brain Metabolism in Healthy Adults","authors":"Mark Moss, Jake Howarth, Holly Moss","doi":"10.1002/hup.70027","DOIUrl":"10.1002/hup.70027","url":null,"abstract":"<p>This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, <i>Genius</i> to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: <i>Genius</i> aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the <i>Genius</i> and sage aroma conditions compared to no aroma with larger effects noted for the <i>Genius</i> blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and <i>Genius</i> blend enhanced metabolism during task performance with a greater impact from the <i>Genius</i> aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive.</p>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C-C motif chemokine ligand 5 (CCL5) and fibroblast growth factor 2 (FGF2) have been increasingly linked to neuroinflammation. This study evaluated the impact of escitalopram on serum CCL5 and FGF2 levels in patients with generalised anxiety disorder (GAD).
Methods
Thirty patients (18–50 years) with GAD diagnosed by DSM-5 criteria, and 30 healthy controls were included. All GAD patients received escitalopram and were followed up for 12 weeks. Serum CCL5 and FGF2 levels were measured before and after escitalopram treatment in GAD patients, with a baseline measurement in healthy controls using ELISA.
Results
We found that serum CCL5 levels were significantly increased (p = 0.001) in GAD patients compared to healthy controls and remained higher after treatment without any significant change. However, serum FGF2 levels were comparable and did not differ significantly between healthy controls and GAD patients before treatment, and increased significantly (p = 0.011) after escitalopram treatment in GAD patients.
Conclusion
In GAD patients, serum levels of CCL5 remained elevated and FGF2 increased significantly post-treatment with escitalopram. This suggests that escitalopram could exert a partial immunomodulatory effect on CCL5 and FGF2, thus modulating inflammation-driven mechanisms of GAD. Future research in larger populations and longer follow-ups is needed to further examine these findings.
{"title":"Immunomodulatory Potential of Escitalopram on C-C Motif Chemokine Ligand 5 and Fibroblast Growth Factor 2 in Patients With Generalised Anxiety Disorder","authors":"Swathi Suresh, Rachna Gupta, Shruti Srivastava, Sumita Halder, Seema Garg","doi":"10.1002/hup.70023","DOIUrl":"10.1002/hup.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>C-C motif chemokine ligand 5 (CCL5) and fibroblast growth factor 2 (FGF2) have been increasingly linked to neuroinflammation. This study evaluated the impact of escitalopram on serum CCL5 and FGF2 levels in patients with generalised anxiety disorder (GAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty patients (18–50 years) with GAD diagnosed by DSM-5 criteria, and 30 healthy controls were included. All GAD patients received escitalopram and were followed up for 12 weeks. Serum CCL5 and FGF2 levels were measured before and after escitalopram treatment in GAD patients, with a baseline measurement in healthy controls using ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that serum CCL5 levels were significantly increased (<i>p</i> = 0.001) in GAD patients compared to healthy controls and remained higher after treatment without any significant change. However, serum FGF2 levels were comparable and did not differ significantly between healthy controls and GAD patients before treatment, and increased significantly (<i>p</i> = 0.011) after escitalopram treatment in GAD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In GAD patients, serum levels of CCL5 remained elevated and FGF2 increased significantly post-treatment with escitalopram. This suggests that escitalopram could exert a partial immunomodulatory effect on CCL5 and FGF2, thus modulating inflammation-driven mechanisms of GAD. Future research in larger populations and longer follow-ups is needed to further examine these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145395385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph C. C. Chen, Rachael L. Sumner, Eric B. Thorstensen, Jacqueline A. Hannam, Nicholas Hoeh, Hafis Adetokunbo Ayeni, Vikrant Singh, Andrew Wilson, Douglas Campbell, Frederick Sundram, Suresh Muthukumaraswamy
Objective
Scopolamine disrupts cholinergic mechanisms via nonspecific muscarinic antagonism. Centrally, excitatory neocortical innervations are antagonised causing spectral electroencephalography (EEG) changes and cognitive impairment. Peripherally, parasympathetic control of heart rate variability (HRV) is disrupted, although acute HRV effects of scopolamine are not well-defined.
Methods
Forty adults with depression received scopolamine hydrobromide (N = 24, 4–6 μg/kg) or glycopyrronium bromide (N = 16, 4–6 μg/kg) infusions. Twelve healthy adults received scopolamine (4–6 μg/kg) infusions. EEG and electrocardiography were recorded across 4 hours post-infusion. EEG spectral, aperiodic, Lempel Ziv complexity (LZC), and microstates analyses were performed. Electrocardiographic HRV metric: proportion of high frequency power (pHF) was calculated and modelled via pharmacokinetic-pharmacodynamic models to ascertain the HRV concentration-effect relationship.
Results
Scopolamine increased delta power between 0.5 and 3.5 h (at 35 min: t = 3.6, p = 0.002). At 3 hours post-infusion, scopolamine increased aperiodic slope (t = −3.4, p = 0.047) and offset (t = −3.93, p = 0.003) parameters, reduced LZC (t = −4.5, p = 2 × 10−4), and microstate D mean duration (t = −3.0, p = 0.039). EEG metrics correlated with drowsiness and alcohol-like stimulant ratings. Peripherally, scopolamine reduced HRV, with two-compartment pharmacokinetic models describing a delayed pHF effect via an effect compartment.
Conclusions
These effects corresponded to increased drowsiness, reduced excitation-inhibition ratio, and reduced HRV—implicating central and peripheral muscarinic mechanisms reminiscent of Alzheimer's-like cholinergic disruption.
Trial Registration
anzctr.org.au identifier: ACTRN12619000569101 and ACTRN12622000228785.
目的：东莨菪碱通过非特异性毒蕈碱拮抗破坏胆碱能机制。中枢，兴奋性新皮质神经支配被拮抗，引起脑电图（EEG）变化和认知障碍。外周，副交感神经对心率变异性（HRV）的控制被破坏，尽管东莨菪碱的急性HRV效应还不明确。方法：40例成人抑郁症患者分别给予氢溴酸东莨菪碱（N = 24, 4 ~ 6 μg/kg）或溴化甘溴铵（N = 16, 4 ~ 6 μg/kg）输注。12名健康成人注射东莨菪碱（4 ~ 6 μg/kg）。记录输注后4小时的脑电图和心电图。进行了脑电图谱、非周期、Lempel Ziv复杂度（LZC）和微态分析。心电图HRV测量：计算高频功率比例（pHF），通过药代动力学-药效学模型建立模型，确定HRV浓度-效应关系。结果：东莨菪碱在0.5 ~ 3.5 h （35 min: t = 3.6, p = 0.002）增加δ功率。在注射后3小时，东莨菪碱增加了非周期斜率（t = -3.4, p = 0.047）和偏移量（t = -3.93, p = 0.003）参数，降低了LZC （t = -4.5, p = 2 × 10-4）和微状态D平均持续时间（t = -3.0, p = 0.039）。脑电图指标与嗜睡和酒精类兴奋剂评级相关。外周，东莨菪碱降低了HRV，双室药代动力学模型描述了通过效应室延迟的pHF效应。结论：这些影响与嗜睡增加，兴奋抑制比降低，以及hrv相关的中枢和外周毒蕈碱机制降低相对应，使人联想到阿尔茨海默病样胆碱能破坏。试验注册：anzctr.org.au标识符：ACTRN12619000569101和ACTRN12622000228785。
{"title":"Scopolamine's Anticholinergic Effects on EEG Spectral, Aperiodic, Complexity, Microstates, and Heart Rate Variability","authors":"Joseph C. C. Chen, Rachael L. Sumner, Eric B. Thorstensen, Jacqueline A. Hannam, Nicholas Hoeh, Hafis Adetokunbo Ayeni, Vikrant Singh, Andrew Wilson, Douglas Campbell, Frederick Sundram, Suresh Muthukumaraswamy","doi":"10.1002/hup.70022","DOIUrl":"10.1002/hup.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Scopolamine disrupts cholinergic mechanisms via nonspecific muscarinic antagonism. Centrally, excitatory neocortical innervations are antagonised causing spectral electroencephalography (EEG) changes and cognitive impairment. Peripherally, parasympathetic control of heart rate variability (HRV) is disrupted, although acute HRV effects of scopolamine are not well-defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty adults with depression received scopolamine hydrobromide (<i>N</i> = 24, 4–6 μg/kg) or glycopyrronium bromide (<i>N</i> = 16, 4–6 μg/kg) infusions. Twelve healthy adults received scopolamine (4–6 μg/kg) infusions. EEG and electrocardiography were recorded across 4 hours post-infusion. EEG spectral, aperiodic, Lempel Ziv complexity (LZC), and microstates analyses were performed. Electrocardiographic HRV metric: proportion of high frequency power (pHF) was calculated and modelled via pharmacokinetic-pharmacodynamic models to ascertain the HRV concentration-effect relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Scopolamine increased delta power between 0.5 and 3.5 h (at 35 min: <i>t</i> = 3.6, <i>p</i> = 0.002). At 3 hours post-infusion, scopolamine increased aperiodic slope (<i>t</i> = −3.4, <i>p</i> = 0.047) and offset (<i>t</i> = −3.93, <i>p</i> = 0.003) parameters, reduced LZC (<i>t</i> = −4.5, <i>p</i> = 2 × 10<sup>−4</sup>), and microstate <i>D</i> mean duration (<i>t</i> = −3.0, <i>p</i> = 0.039). EEG metrics correlated with drowsiness and alcohol-like stimulant ratings. Peripherally, scopolamine reduced HRV, with two-compartment pharmacokinetic models describing a delayed pHF effect via an effect compartment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These effects corresponded to increased drowsiness, reduced excitation-inhibition ratio, and reduced HRV—implicating central and peripheral muscarinic mechanisms reminiscent of Alzheimer's-like cholinergic disruption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>anzctr.org.au identifier: ACTRN12619000569101 and ACTRN12622000228785.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marina Krylova, Sarah Alizadeh, Hamidreza Jamalabadi, Igor Izyurov, Tara Chand, Johan van der Meer, Johannes C. Vester, Britta Naschold, Myron Schultz, Veronika Engert, Martin Walter
Objective
Stress from daily psychosocial challenges is a significant health concern with limited pharmacological treatment options. Psychosocial stress triggers distinct responses in the autonomic and central nervous systems, measurable via heart rate variability (HRV) and electroencephalogram (EEG). This post hoc analysis of clinical trial data explores the impact of the anti-stress medication Neurexan (Nx4) on HRV and EEG signals, and their correlation in a resting state following acute psychosocial stress induction.
Methods
Data from the NEURIM trial (NCT02602275), a randomized, placebo-controlled, double-blind, cross-over study, were utilized. Participants received Nx4 before exposure to ScanSTRESS, a psychosocial stress paradigm. EEG and photoplethysmogram data were collected at rest before and after stress exposure. Stress responsivity under both placebo and Nx4 conditions was evaluated through HRV and EEG signals.
Results
Psychosocial stress altered HRV parameters (increased LF/HF ratio, elevated Baevsky's Stress Index, reduced RMSSD) and EEG activity (decreased aperiodic offset, increased alpha power). Nx4 significantly mitigated stress-induced changes in LF/HF ratio, Baevsky's Stress Index, and aperiodic offset. A significant correlation was observed between Nx4 effects on HRV and EEG activity.
Conclusion
Nx4 attenuates peripheral and central physiological stress responses, suggesting a comprehensive approach to mitigating stress responses in daily life.
{"title":"Comprehensive Mitigation of Peripheral and Central Stress Responses by Nx4: Insights From EEG and Heart Rate Variability in Post-Stress Resting State","authors":"Marina Krylova, Sarah Alizadeh, Hamidreza Jamalabadi, Igor Izyurov, Tara Chand, Johan van der Meer, Johannes C. Vester, Britta Naschold, Myron Schultz, Veronika Engert, Martin Walter","doi":"10.1002/hup.70020","DOIUrl":"10.1002/hup.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stress from daily psychosocial challenges is a significant health concern with limited pharmacological treatment options. Psychosocial stress triggers distinct responses in the autonomic and central nervous systems, measurable via heart rate variability (HRV) and electroencephalogram (EEG). This post hoc analysis of clinical trial data explores the impact of the anti-stress medication Neurexan (Nx4) on HRV and EEG signals, and their correlation in a resting state following acute psychosocial stress induction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from the NEURIM trial (NCT02602275), a randomized, placebo-controlled, double-blind, cross-over study, were utilized. Participants received Nx4 before exposure to ScanSTRESS, a psychosocial stress paradigm. EEG and photoplethysmogram data were collected at rest before and after stress exposure. Stress responsivity under both placebo and Nx4 conditions was evaluated through HRV and EEG signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Psychosocial stress altered HRV parameters (increased LF/HF ratio, elevated Baevsky's Stress Index, reduced RMSSD) and EEG activity (decreased aperiodic offset, increased alpha power). Nx4 significantly mitigated stress-induced changes in LF/HF ratio, Baevsky's Stress Index, and aperiodic offset. A significant correlation was observed between Nx4 effects on HRV and EEG activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Nx4 attenuates peripheral and central physiological stress responses, suggesting a comprehensive approach to mitigating stress responses in daily life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>William MacArthur (‘Billy’) Mackenzie died alongside an apologetic suicide note, in a garden shed at his father's cottage in Auchterhouse, Scotland, after an overdose of amitriptyline, beta-blockers and paracetamol. He was 64 days short of his fortieth birthday. Three weeks earlier, on New Years Eve 1996, he had been admitted to Ninewells Hospital, Dundee, requiring assisted ventilation after consuming a large quantity of prescribed hypnotics. Then, his father had entreated the assessing psychiatrist to transfer his son to the hospital psychiatry ward, but Billy had maintained the overdose was an ‘accident’, so he was instead discharged home with a recommendation to start antidepressants.</p><p>Some 15 years previously, Mackenzie stood at the threshold of international success (Doyle <span>1998</span>). With his musical collaborator Alan Rankine, as ‘The Associates’, the band had released six singles over the preceding 12 months, to increasing critical acclaim: their mysterious, fragmented lyrics and disconcerting melodic shifts somehow captured both the desolate landscapes and agitated unease of post-industrial Thatcher-ravaged Britain. What promised to be an <i>annus mirabilis</i> in 1982 saw the band appear repeatedly on BBC's <i>Top of the Pops</i> and featured adoringly in glossy teen mags. Highbrow music newspaper journalists described their third album (<i>Sulk</i>), released in May, as ‘an elusive butterfly’, yet possessing a ‘timeless majesty’. It stayed high in the album charts for 20 weeks. But in October Mackenzie threw it all away, by declining to perform publicly - so causing the departure of an exasperated Rankine - on the eve of a widely anticipated tour of British concert venues.</p><p>Admittedly, from an early age Mackenzie was given to choosing impulsively and acting recklessly, and gushing public praise fitted poorly with his dismissive self-criticism. He had a track record of doing crazy things: as a teenager, marrying an American presumptive heiress in Las Vegas; whilst recording, consuming so many psychostimulants as to require 3 days' cardiac monitoring in St Mary's Hospital, London. But there were additional factors in this career-damaging decision. Although an impish grin, flirtatious manner and occasional camp pugnaciousness suggested a cool ease in public encounters, by 1978 he had become troubled by recurring ‘stage fright’ immediately prior to performance. The lyrics to The Associates' best-known song <i>Party Fears Two</i> (a top-10 single) can be read as a description of debilitating social anxiety and the temporary relief afforded by alcohol consumption. However, it was only after many years that could Mackenzie confide about his experience of disabling panic: by then, it was hard to board flights, or to be separated far from his mother Lily, to whom he was devoted.</p><p>The 15 years from <i>Sulk</i> should not be regarded simply as a sad, slow decline. A succession of collaborations under the continuing name
威廉·麦克阿瑟（“比利”）·麦肯齐死于他父亲位于苏格兰奥斯特豪斯别墅的花园小屋里，死前留下了一封道歉遗书。他生前服用了过量的阿米替林、受体阻滞剂和扑热息痛。他离40岁生日还有64天。三周前，1996年新年前夜，他住进了邓迪的Ninewells医院，在服用了大量处方催眠药后需要辅助呼吸。然后，他的父亲恳求评估的精神科医生将他的儿子转移到医院的精神科病房，但比利坚持认为过量服用是一个“意外”，所以他出院回家，并建议他开始服用抗抑郁药。大约15年前，麦肯齐站在国际成功的门槛上（Doyle 1998）。与他的音乐合作伙伴阿兰·兰金（Alan Rankine）合作的“The Associates”乐队在过去的12个月里发行了6首单曲，获得了越来越多的好评：他们神秘、支离破碎的歌词和令人不安的旋律变化，不知怎么地捕捉到了后工业时代撒切尔夫人肆虐的英国荒凉的风景和不安的不安。1982年被认为是奇迹之年，乐队多次出现在英国广播公司（BBC）的《流行之巅》（Top of the pop）节目中，并在光鲜的青少年杂志上刊登了可爱的照片。高深的音乐报纸记者形容他们5月发行的第三张专辑《Sulk》是“一只难以捉摸的蝴蝶”，却拥有“永恒的威严”。这首歌在专辑排行榜上保持了20周的高位。但在10月，麦肯齐抛弃了这一切，在万众期待的英国音乐会场地巡回演出前夕，他拒绝公开演出——这导致了恼怒的兰金离开。诚然，麦肯齐从小就有冲动和鲁莽的选择，对公众的溢于言表的赞扬与他轻蔑的自我批评极不相称。他有做疯狂事情的记录：十几岁时，在拉斯维加斯娶了一位美国女继承人；在录音的同时，服用了太多的精神兴奋剂，需要在伦敦圣玛丽医院进行3天的心脏监测。但在这个有损职业生涯的决定中，还有其他因素。尽管顽皮的咧嘴笑、轻浮的举止和偶尔的好斗表现出他在公众场合的冷静从容，但到1978年，他在演出前就被反复出现的“怯场”所困扰。The Associates乐队最著名的歌曲《Party Fears Two》（排名前十的单曲）的歌词可以解读为对社交焦虑的描述，以及饮酒带来的暂时缓解。然而，直到多年以后，麦肯齐才吐露了他的恐慌经历：那时，他很难登机，也很难远离他深爱的母亲莉莉。愠怒后的15年不应被简单地视为一个悲伤的、缓慢的衰退。他以“联合乐队”的名义进行了一系列的合作，并与其他音乐家一起客串演出，这让观众想起了他独特的嗓音，他可以在一句台词内从男中音到假声灵巧地转换。然而，随后的专辑（1985年的《maybe》；1990年的《Wild and Lonely》）将它们迷人的时刻置于过度制作的材料中：当能量更高的歌曲在纽约夜总会成为fêted时，发行的单曲最多只是小热门。评论家们转而质疑这支乐队的持续意义。长期以来，在没有财务精明的经理监督和私人助理保护的情况下，麦肯齐一直在苦苦挣扎，当他做出这样的任命时，已经太晚了。由于录制费用超出预算，但商业上的成功有限，这支“乐队”被连续几家公司放弃。联合乐队的专辑《The Glamour Chase》于1988年首次录制，最终在麦肯齐去世五年后发行。麦肯齐被一种令人无能的完美主义所困扰，他对自己的声乐作品一直不满，对音乐行业的机构也逐渐感到痛苦。对发际线明显后退的敏感使他不愿出现在公众面前。以他的名字命名的第一张专辑（Outernational, 1992）不知怎么地将他的个性淹没在冰川般的过度乐器之下，可能只卖了3000张（Doyle 1998）。1993年，他们半心半意地与兰金重逢，制作了一些很有前途的材料（被描述为“科技哥特-噩梦般的黑暗”），但在20世纪90年代初的英国流行怀旧风潮中，这种前卫并不受到唱片公司的欢迎。麦肯齐继续与值得信赖的合作者创作新歌，但似乎无法确定一种融合的风格，在钢琴民谣和吉他嗡嗡作响的摇滚歌曲之间摇摆不定；没有合同就没有创意出口。由于从未学会在经济能力范围内生活，他的公寓在1995年4月被收回，麦肯齐被宣布破产。 1996年初，他的母亲被诊断出胃癌晚期，麦肯齐开始强迫性地吸烟。7月的一天，当她的病情突然恶化时，他从爱丁堡赶回家，但在他到达之前，她已经去世了。尽管他会聊上几个小时，但家人和朋友们都觉得他无法表达出他的悲伤。在她去世两周后的最后一次采访中，麦肯齐承认自己一直不太愿意当明星，并隐晦地承认了自己的双性恋身份，他还谈到了自己想要连续发行三张不同类型的专辑的愿望。出乎意料的是，他得到了一份基于钢琴民谣小样的录音合同，并于10月开始录制Beyond The Sun，这是他一生中完成的最后一张专辑。他的最后一张唱片是去年12月与利物浦电子乐队Apollo 440合作录制的《Pain in Any Language》的人声。那时他已经开始渐渐衰弱了。麦肯齐现在和父亲住在一起，往返于邓迪和伦敦之间的火车让他精疲力竭。朋友们开始担心他明显的孤独、孤僻，以及他让母亲失望的想法。麦肯齐变得不愿意独自一人，也不愿意和别人一起离开家，他说自己无法入睡。很容易想象，在服用过量安眠药后，麦肯齐巧舌如舌地说服医院精神病医生允许他回家：而且那天是银行假日，医院里没什么事发生。但在认识到麦肯齐患有抑郁症，需要抗抑郁药物治疗后，她随后开出的阿米替林“上了膛的枪”——外加β受体阻滞剂——让人难以理解。综合评估表明麦肯齐有进一步自杀企图的风险。阿米替林在过量时的高心脏毒性早已被证实并广为人知(Montgomery et al. 1989) -并且确实仍然是一个值得关注的原因（Taylor et al. 2024）。如果在服用过量药物之前，麦肯齐在寻求治疗持续性失眠症时首次开了抗抑郁药，那么事件的发展过程可能会有所不同。也许阿米替林的推荐是相信它可以促进睡眠，而β受体阻滞剂的添加是认为它可以抑制躁动，尽管许多更安全的替代品（特别是选择性血清素再摄取抑制剂）是现成的。但是选择的药物并没有起作用。失眠加剧，体重下降，幽默感下降，他告诉朋友自己出现了幻觉。他开始休假：他试图为他的音乐合作者提供经济支持，并在他虚弱的祖母家中唱歌。在麦肯齐去世的前一天，他告诉他的父亲他要去邓迪，但他留在奥斯特豪斯，最后一次被看到他可能还活着，披着羽绒被在他父亲家上方的田野里徘徊。这既是哀歌，也是颂词。麦肯齐最快乐的事情可能是他珍爱的饲养惠比特狗的事业，他经常开玩笑说，他和他的音乐作品很快就会被遗忘。但当《Beyond the Sun》在他去世9个月后发行时，它获得了多项赞誉，包括“必不可少”（每日电讯报）和“完美绝伦”（Melody Maker）。它的销售利润被直接捐给了麦克米伦癌症救济和撒玛利亚人。现在听起来，这首歌似乎写得相当匆忙。麦肯齐需要更多的时间来培养他的歌曲创作，并与敏感的合作者分享他辉煌的四八度音域。2007年3月，在伦敦举行的10周年纪念音乐会上，人们普遍认为，他只不过是过早出生了10年。我们还是得听听他的声音。作者声明无利益冲突。
{"title":"Billy Mackenzie: Sometimes Wild, Often Lonely","authors":"David Baldwin","doi":"10.1002/hup.70021","DOIUrl":"https://doi.org/10.1002/hup.70021","url":null,"abstract":"<p>William MacArthur (‘Billy’) Mackenzie died alongside an apologetic suicide note, in a garden shed at his father's cottage in Auchterhouse, Scotland, after an overdose of amitriptyline, beta-blockers and paracetamol. He was 64 days short of his fortieth birthday. Three weeks earlier, on New Years Eve 1996, he had been admitted to Ninewells Hospital, Dundee, requiring assisted ventilation after consuming a large quantity of prescribed hypnotics. Then, his father had entreated the assessing psychiatrist to transfer his son to the hospital psychiatry ward, but Billy had maintained the overdose was an ‘accident’, so he was instead discharged home with a recommendation to start antidepressants.</p><p>Some 15 years previously, Mackenzie stood at the threshold of international success (Doyle <span>1998</span>). With his musical collaborator Alan Rankine, as ‘The Associates’, the band had released six singles over the preceding 12 months, to increasing critical acclaim: their mysterious, fragmented lyrics and disconcerting melodic shifts somehow captured both the desolate landscapes and agitated unease of post-industrial Thatcher-ravaged Britain. What promised to be an <i>annus mirabilis</i> in 1982 saw the band appear repeatedly on BBC's <i>Top of the Pops</i> and featured adoringly in glossy teen mags. Highbrow music newspaper journalists described their third album (<i>Sulk</i>), released in May, as ‘an elusive butterfly’, yet possessing a ‘timeless majesty’. It stayed high in the album charts for 20 weeks. But in October Mackenzie threw it all away, by declining to perform publicly - so causing the departure of an exasperated Rankine - on the eve of a widely anticipated tour of British concert venues.</p><p>Admittedly, from an early age Mackenzie was given to choosing impulsively and acting recklessly, and gushing public praise fitted poorly with his dismissive self-criticism. He had a track record of doing crazy things: as a teenager, marrying an American presumptive heiress in Las Vegas; whilst recording, consuming so many psychostimulants as to require 3 days' cardiac monitoring in St Mary's Hospital, London. But there were additional factors in this career-damaging decision. Although an impish grin, flirtatious manner and occasional camp pugnaciousness suggested a cool ease in public encounters, by 1978 he had become troubled by recurring ‘stage fright’ immediately prior to performance. The lyrics to The Associates' best-known song <i>Party Fears Two</i> (a top-10 single) can be read as a description of debilitating social anxiety and the temporary relief afforded by alcohol consumption. However, it was only after many years that could Mackenzie confide about his experience of disabling panic: by then, it was hard to board flights, or to be separated far from his mother Lily, to whom he was devoted.</p><p>The 15 years from <i>Sulk</i> should not be regarded simply as a sad, slow decline. A succession of collaborations under the continuing name ","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Loss of function mutations in the WFS1 gene cause Wolfram syndrome, which is characterized by juvenile-onset diabetes mellitus, diabetes insipidus, neurodegeneration, hearing loss and optic nerve atrophy. Psychiatric symptoms, including major depression and suicidal behavior, are common in this disorder. WFS1 mutations induce this condition through altering interactions between the endoplasmic reticulum and mitochondria, resulting in diminished Ca2+ import that leads to mitochondrial dysfunction. Quite recently, it was shown that such impaired Ca2+ transport could be restored by the experimental σ1 receptor agonist PRE084. In animal models of Wolfram syndrome, this compound restored the behavioral phenotype. Based on these previous data, we propose that Wolfram syndrome may serve as a mechanistically informative model for exploring σ1 receptor modulation, mitochondrial dysfunction, and affective symptoms. This proposal is based on four arguments. Firstly, the R-enantiomer of ketamine exhibits largely selective binding to the σ1 receptor as an agonist. Secondly, R-ketamine and other σ1 agonists display antidepressant-like activity in rodent depression models. Thirdly, while both S- and R-ketamine hold potential for reducing suicidal behavior, the latter is likely to have a lower potential for abuse and fewer side effects. Fourth, Wolfram syndrome is characterized by mitochondrial dysfunction, which has also been linked to depression.
{"title":"Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective","authors":"Hans O. Kalkman, Lukasz Smigielski","doi":"10.1002/hup.70019","DOIUrl":"10.1002/hup.70019","url":null,"abstract":"<p>Loss of function mutations in the <i>WFS1</i> gene cause Wolfram syndrome, which is characterized by juvenile-onset diabetes mellitus, diabetes insipidus, neurodegeneration, hearing loss and optic nerve atrophy. Psychiatric symptoms, including major depression and suicidal behavior, are common in this disorder. <i>WFS1</i> mutations induce this condition through altering interactions between the endoplasmic reticulum and mitochondria, resulting in diminished Ca<sup>2+</sup> import that leads to mitochondrial dysfunction. Quite recently, it was shown that such impaired Ca<sup>2+</sup> transport could be restored by the experimental σ1 receptor agonist PRE084. In animal models of Wolfram syndrome, this compound restored the behavioral phenotype. Based on these previous data, we propose that Wolfram syndrome may serve as a mechanistically informative model for exploring σ1 receptor modulation, mitochondrial dysfunction, and affective symptoms. This proposal is based on four arguments. Firstly, the R-enantiomer of ketamine exhibits largely selective binding to the σ1 receptor as an agonist. Secondly, R-ketamine and other σ1 agonists display antidepressant-like activity in rodent depression models. Thirdly, while both S- and R-ketamine hold potential for reducing suicidal behavior, the latter is likely to have a lower potential for abuse and fewer side effects. Fourth, Wolfram syndrome is characterized by mitochondrial dysfunction, which has also been linked to depression.</p>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bupropion, a norepinephrine and dopamine reuptake inhibitor, is FDA-approved for depression and smoking cessation but not for anxiety disorders. Its role in patients with comorbid depression and anxiety remains debated. This review examines bupropion's potential anxiolytic and/or anxiogenic effects. Clinical trials suggest bupropion may reduce anxiety symptoms in depressed patients, showing comparable efficacy to SSRIs and SNRIs in mild to moderate anxiety. However, its stimulating properties can also provoke anxiety, particularly at higher doses. While some studies indicate no significant difference in anxiolytic efficacy between bupropion and serotonergic antidepressants, others suggest SSRIs may be preferable for severe depression with anxious distress. Emerging data hint at potential benefits for generalized and social anxiety disorders, though findings remain inconclusive. Given its mixed effects, a cautious approach is recommended. Initiating treatment at lower doses and monitoring for anxiogenic symptoms can help optimize outcomes. Further research is needed to clarify bupropion's potential role in anxiety management and its comparative efficacy against standard treatments.
{"title":"Bupropion and Anxiety: A Brief Review","authors":"Sean E. Oldak, Anthony J. Maristany","doi":"10.1002/hup.70018","DOIUrl":"10.1002/hup.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>Bupropion, a norepinephrine and dopamine reuptake inhibitor, is FDA-approved for depression and smoking cessation but not for anxiety disorders. Its role in patients with comorbid depression and anxiety remains debated. This review examines bupropion's potential anxiolytic and/or anxiogenic effects. Clinical trials suggest bupropion may reduce anxiety symptoms in depressed patients, showing comparable efficacy to SSRIs and SNRIs in mild to moderate anxiety. However, its stimulating properties can also provoke anxiety, particularly at higher doses. While some studies indicate no significant difference in anxiolytic efficacy between bupropion and serotonergic antidepressants, others suggest SSRIs may be preferable for severe depression with anxious distress. Emerging data hint at potential benefits for generalized and social anxiety disorders, though findings remain inconclusive. Given its mixed effects, a cautious approach is recommended. Initiating treatment at lower doses and monitoring for anxiogenic symptoms can help optimize outcomes. Further research is needed to clarify bupropion's potential role in anxiety management and its comparative efficacy against standard treatments.</p>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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