Human Psychopharmacology: Clinical and Experimental最新文献

{"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}

{"title":"Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective","authors":"Hans O. Kalkman,&nbsp;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 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.</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}

{"title":"Bupropion and Anxiety: A Brief Review","authors":"Sean E. Oldak,&nbsp;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}

{"title":"The Efficacy and Safety of Amyloid Beta-Directed Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials","authors":"Yun Wei,&nbsp;Hualing Li","doi":"10.1002/hup.70017","DOIUrl":"https://doi.org/10.1002/hup.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a leading cause of mortality worldwide. One of the newer treatments for AD is amyloid beta (Aβ) directed monoclonal antibodies (mAbs). This systematic review and meta-analysis aimed to assess the efficacy and safety of this class of drugs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted across Scopus, Web of Science, PubMed, and the Cochrane Library until January 30, 2025, focusing on phase III randomized controlled trials (RCTs) evaluating anti-Aβ mAbs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve RCTs with 24 arms were included. Anti-Aβ mAbs significantly reduced the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score (mean difference (MD): −0.16, 95% confidence interval (CI) (−0.29, −0.04)), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score (MD: −0.87, 95% CI (−1.13, −0.60)), and amyloid positron emission tomography (PET) standardized uptake value ratio (SUVR) (MD: −0.11, 95% CI (−0.19, −0.02)). They also significantly increased the Mini-Mental State Examination (MMSE) score (MD: 0.31, 95% CI (0.15, 0.46)) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score (MD: 1.21, 95% CI (0.89, 1.53)). However, they were associated with a significant increase in complications, including amyloid-related imaging abnormalities-edema/effusion (ARIA-E) (odds ratio (OR): 10.20, 95% CI (7.17, 14.50)), ARIA-hemosiderosis or microhemorrhage (ARIA-H) (OR: 1.75, 95% CI (1.22, 2.50)), and any adverse events (OR: 1.22, 95% CI (1.08, 1.38), I²: 48.59%)). The subgroup analysis showed that treatment administered in the early/preclinical stages of AD resulted in a greater reduction in CDR-SB and ADAS-Cog scores, as well as in amyloid burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Anti-Aβ mAbs offer modest clinical benefits, and pose some serious complications, necessitating a cautious approach to their prescription.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058072","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}

{"title":"Effects of Cannabinoids on Emotional States and Alcohol Use Among Underrepresented Groups: Moderation by Perceived Discrimination","authors":"Renée Martin-Willett,&nbsp;Carillon J. Skrzynski,&nbsp;Angela D. Bryan,&nbsp;L. Cinnamon Bidwell","doi":"10.1002/hup.70016","DOIUrl":"https://doi.org/10.1002/hup.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study examined the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) on negative mood and drinking behaviors, and whether those effects were moderated by levels of perceived discrimination among participants who identify with a racial, ethnic, gender, or sexual identity that is underrepresented in research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were either not using cannabis, using cannabis with THC, or using cannabis with CBD and were assessed at baseline, 2 weeks, and 4-weeks following <i>ad libitum</i> use of a legal market cannabis product that was randomly assigned to them. Primary outcomes included scores on the Depression Anxiety Stress (DASS) Scale and number of drinking days. Moderation analyses used the Perceived Discrimination Scale (PDS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>172 participants who were 62% female and mean age = 30.2 were included (not using cannabis = 20, using cannabis = 152; of those, THC = 96, CBD = 56). There were significant changes in DASS scores over time, with participants using CBD experiencing greater decreases in symptoms versus participants using THC. There was also a marginal conditionXtimeXPDS interaction that was significant when the condition not using cannabis was removed from the analysis. In this case, participants in the CBD and THC conditions shared a general linear trend of decreasing DASS total scores over time, but only at average (mean) and high (+1 SD) levels of PDS scores. There were no significant effects on alcohol-related outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CBD may be helpful in reducing negative emotional symptoms in the short term without increasing risk for disordered alcohol use, and perceived discrimination plays a significant role in this relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Clinicaltrials. gov (NCT03491384; Registration Date 2018-02-28); Open Science Framework</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012309","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}

{"title":"National Prescribing Trends and Cost Analysis of Antidepressants, Anxiolytics, and Hypnotics in England, 2010–2023","authors":"Mike Stedman,&nbsp;Mark Davies,&nbsp;John Warner- Levy,&nbsp;Joseph Ingram,&nbsp;David Taylor,&nbsp;Adrian Heald","doi":"10.1002/hup.70011","DOIUrl":"https://doi.org/10.1002/hup.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>We describe prescribing of anxiolytics/hypnotics/antidepressants at an all-England level between 2010 and 2023, taking account of the influence of the COVID-19 pandemic-period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All Primary Care Prescribing data for England for anxiolytics/hypnotics/antidepressant agents taken as tablets or capsules from 1 January 2010 to 31 December 2023 were considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Antidepressants: the greatest increases were in sertraline prescriptions increasing from 2.9million 2010 by 685% to 23.0 million-2023; duloxetine increased by 545% to 3.9million prescriptions; mirtazapine by 269% to 12.4million prescriptions. Regarding cost, overall average cost fell 2010-2023 by 54% from £4.86(Euros 5.68) to £2.25(Euros 2.63) per prescription. Anxiolytics: the number of prescriptions for anxiolytics fell 6.5–4.8 m (−27%) overall, with all anxiolytics falling except buspirone. The greatest period of fall was seen between 2018 and 2023. Lorazepam/diazepam/chlordiazepoxide were down 23%,16%, 88% respectively. Average cost of prescriptions fell by 13% to £3.20(Euros 3.74). Hypnotics: the number of prescriptions for hypnotics fell 41% from 9.8million to 5.8million in 2023. All prescriptions fell in number. Annual trends showed no deviations for the COVID-19 core pandemic (2020/2021) years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall trends demonstrate a more than doubling of antidepressant prescribing over the period 2010–2023, with similar volume reduction in anxiolytics/hypnotics over the same period. Such real world data facilitate the development of policy influencing insights for psychotropic prescribing management now and in coming years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861920","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}

{"title":"Becoming More Precise in Psychiatry: Signposts, Destinations, Maps and Territories","authors":"Milica M. Nestorovic,&nbsp;David S. Baldwin","doi":"10.1002/hup.70013","DOIUrl":"https://doi.org/10.1002/hup.70013","url":null,"abstract":"<p>The metaphorical expression ‘<i>Don't mistake the signpost for the destination</i>’ cautions against the dual pitfalls of becoming over-preoccupied with the details of a route and of being prematurely encouraged by interim way-posts, when undertaking an adventurous journey towards a cherished goal. In psychiatric practice, patients with mental health problems and their attending professionals from varying disciplines still yearn for the targeted discovery and routine implementation of individually tailored approaches, designed to shorten the course of illness and improve other clinical outcomes. This personalised medicine approach, which underpins the ‘precision psychiatry’ movement (Fernandes et al. <span>2017</span>), has the laudable ambition of ‘getting the right treatment to the right patient at the right time’, and has gained additional momentum through the recent publication of the Precision Psychiatry Roadmap (PPR) (Kas et al. <span>2025</span>), constructed by a consortium including patient organisations, clinicians, scientists, industrial representatives and regulatory agencies. Its carefully crafted eight sub-components, five phases (envisaged to occur over at least 15 years) and 10 anticipated future implementation steps together provide a detailed plan, for incorporating biology-informed evidence into symptom-based diagnoses so allowing for the discovery, development and deployment of mechanism-based treatments for patients with mental disorders, designed to be more effective and acceptable than current approaches. So, how useful might such a ‘map’ be?</p><p>It is worth considering two fundamental challenges. First, idioms of psychological distress vary between individuals and across cultures, patients offer psychological complaints to clinicians in variable ways, and health professionals differ in their preferred style in asking direct questions about key symptoms necessary for accurate psychiatric diagnosis. For example, even within a single country, there is worrying variation between mental health services in the comprehensiveness of patient assessment in anxiety and depressive disorders, leading to concerns about the validity and reliability of recorded psychiatric diagnosis (Baldwin et al. <span>2021</span>). In addition, reporting of psychological symptoms is affected by illness-related difficulties in recollection and processing of emotional information (Jongs et al. <span>2022</span>). It seems probable that ‘biology-informed evidence’ could only help to supplement and refine treatment decisions based on symptom-based diagnoses when symptoms are sought and evaluated in a standardised but culturally sensitive manner, through structured clinical interviews and robust psychometric rating scales. Second, whilst the PPR authors rightly acknowledge the importance of evaluating the individual ‘exposome’—which incorporates detailed consideration of personal factors such as socioeconomic status, lived environment, trauma exposure,","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681547","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}

{"title":"Allopregnanolone Concentrations After Ascending Single Dose Administration of Progesterone to Healthy Volunteers","authors":"Natalie J. Hughes-Medlicott,&nbsp;Hoang Nguyen,&nbsp;Paul Glue,&nbsp;Yoram Barak","doi":"10.1002/hup.70012","DOIUrl":"https://doi.org/10.1002/hup.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Postpartum depression (PPD) is associated with significant morbidity and mortality. It affects as many as 11.5% of women giving birth. Allopregnanolone (an endogenous progesterone metabolite) has been a promising avenue of clinical research for the treatment of PPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the pharmacokinetics of allopregnanolone (Allo) following orally dosed progesterone in healthy volunteers. Secondary outcome was calculating the daily dose of progesterone needed to achieve the clinically meaningful concentration of 50 ng/mL Allo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single ascending dose study to measure plasma concentrations of Allo after 200, 400 and 600 mg doses of extended-release progesterone capsules. Secondary outcome was the safety and tolerability of extended-release progesterone capsules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We recruited 10 participants, 9 male and 1 female, mean (SD) age 38.7 (18.7) years. The maximum plasma concentration (<i>C</i>_max) of Allo was observed at 2 h. A linear relationship was fitted to the observations. Sedation was assessed at baseline, 1, 2, 4, 6 and 8 h after each dose. Sedation ratings increased at 1–2 h post-dose after all three progesterone doses, with the greatest increase after the 600 mg dose, and fell subsequently. Vital signs were unchanged, and no other adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this single ascending dose study has clarified that 400 mg four times/day of progesterone is required to achieve maximum plasma ALLO concentrations of 50 ng/mL. Tolerability and safety were acceptable for all doses of progesterone tested.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681548","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}

{"title":"How Should Non-Prescribed Use of Gabapentinoids be Reduced in Psychiatric Practice?","authors":"Giada Lorenzi,&nbsp;David S. Baldwin","doi":"10.1002/hup.70010","DOIUrl":"https://doi.org/10.1002/hup.70010","url":null,"abstract":"&lt;p&gt;Gabapentinoids are a group of medications used for treating patients with a limited range of neurological or psychiatric conditions: some (gabapentin and pregabalin) have entered widespread clinical use, due to their analgesic, anticonvulsant and anxiolytic effects. Licenced indications for these drugs vary across countries: for example, within the United Kingdom (UK), gabapentin does not have a market authorisation for treating patients with psychiatric disorders, although it is licenced for treatment of focal seizures, peripheral neuropathic pain, menopausal symptoms in women with breast cancer, oscillopsia and spasticity in multiple sclerosis, and muscular symptoms in motor neuron disease. By contrast, pregabalin has a license for generalized anxiety disorder (GAD), and for treating patients with peripheral or central neuropathic pain, and as an adjunctive therapy in patients with focal seizures: however, it is not licenced for GAD within the United States. Since introduction, gabapentin and pregabalin have become often prescribed outside the terms of their market authorisations in many countries: at least half of all gabapentinoid prescriptions in the UK may be ‘off-label’ [Montastruc et al. &lt;span&gt;2018&lt;/span&gt;], and concerns regarding widespread non-prescribed use (with some fatalities) led to their reclassification as Class C controlled substances with accompanying regulations regarding prescriptions, in April 2019. Since this reclassification, further data on potential hazards associated with non-prescribed use of gabapentinoids have accumulated [Baldwin and Masdrakis &lt;span&gt;2022&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Findings from epidemiological studies and systematic reviews indicate that the prevalence of non-prescribed gabapentinoid use is not insubstantial: for example, in populations without a history of substance misuse the prevalence of non-prescribed use of pregabalin may lie between 0.5% and 8.5% among those dispensed the drug [Schjerning et al. &lt;span&gt;2016&lt;/span&gt;]. A range of risk factors for non-prescribed use for gabapentinoids have been identified: individuals with a history of substance use disorders are at greater risk, particularly those with a history of opiate use or poly-substance use. Other possible risk factors for non-prescribed use include younger age, male sex, a diagnosis of anxiety, access to multiple prescribers, and physical illness including cancer, multiple sclerosis and neuropathy [Driot et al. &lt;span&gt;2019&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;There are multiple hazards associated with non-prescribed use of gabapentinoids [Baldwin and Masdrakis &lt;span&gt;2022&lt;/span&gt;]. Non-prescribed ‘overuse’ of gabapentin is associated with increased risks of all-cause and drug-related hospitalisation, particularly if combined with opioids, and pregabalin prescriptions in patients undergoing opioid maintenance therapy may increase all-cause mortality: increased risk of death may result from respiratory depression, prolonged gastrointestinal transit increasing gabapentin conc","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606628","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}

{"title":"Efficacy of Intranasal Esketamine in Treatment-Resistant Depression: A Six-Month Real-World Follow-Up Study of Depressive Symptoms, Hopelessness, and Suicide Risk","authors":"Maurizio Pompili,&nbsp;Maria Anna Trocchia,&nbsp;Ludovica Longhini,&nbsp;Eva Dispenza,&nbsp;Cristina Di Legge,&nbsp;Salvatore Sarubbi,&nbsp;Denise Erbuto,&nbsp;Isabella Berardelli","doi":"10.1002/hup.70008","DOIUrl":"https://doi.org/10.1002/hup.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Treatment-resistant depression is one of the most significant clinical challenges in psychiatric practice. The primary aim of the present study was to assess the efficacy and tolerability of intranasal esketamine on depressive symptoms in a real-world outpatient setting. A secondary objective was to explore the potential benefits of intranasal esketamine on hopelessness and suicide risk (suicidal ideation and suicide attempts).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-one patients diagnosed with treatment-resistant depression were treated with intranasal esketamine. Depressive symptoms (MADRS and BDI), suicide risk (C-SSRS), and hopelessness (BHS) were assessed. We conducted a mixed model for repeated measures analysis to evaluate changes from baseline (T0), 3-month follow-up (T1), and 6-month follow-up (T2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results indicated that depressive symptoms decreased over time. Specifically, both clinician and self-report measures show lower levels of depressive symptoms at 3-month and 6-month follow-up. We also found a significant decrease in the presence of suicidal ideation between T0 and T2. Finally, patients also reported a reduction in hopelessness levels over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate an overall response regarding depressive symptoms, hopelessness, and suicidal ideation after esketamine in treatment-resistant depression at 3-month and 6-month follow-up assessments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582298","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}