Human Psychopharmacology: Clinical and Experimental最新文献

{"title":"Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Psychological Well-Being and Depressive Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","authors":"Tsung-Hsuan Hung,&nbsp;Chyi-Rong Chen,&nbsp;Chih-Wei Hsu,&nbsp;Andre F. Carvalho,&nbsp;Brendon Stubbs,&nbsp;Ping-Tao Tseng,&nbsp;Liang-Jen Wang,&nbsp;Pao-Yen Lin","doi":"10.1002/hup.70041","DOIUrl":"10.1002/hup.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders. Howeve, their effects on depressive symptoms and psychological well-being remain uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effects of GLP-1RAs on depressive symptoms and psychological well-being. Random-effects models were used to calculate standardized mean differences (SMDs). Subgroup and meta-regression analyses were performed to explore heterogeneity. The protocol was registered with PROSPERO (CRD42024566217).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 25 trials (17,751 participants) evaluated psychological well-being and 11 trials (1961 participants) evaluated depressive symptoms. GLP-1RA treatment was associated with a small but significant improvement in psychological well-being compared with control conditions (SMD = 0.374, 95% CI 0.093–0.656), whereas no significant effect was observed for depressive symptoms (SMD = 0.079, 95% CI −0.024–0.182). Improvements in psychological well-being were consistently observed in studies using semaglutide, tirzepatide or liraglutide, subcutaneous administration, and in populations with type 2 diabetes mellitus or obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GLP-1RA treatment was associated with modest improvements in psychological well-being but not depressive symptoms. These findings should be interpreted cautiously and suggest that any observed psychological benefits are likely indirect, potentially reflecting improvements in metabolic status or general health, rather than direct mood-improving effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583534","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":"Comparison of Hip Fracture Risk Between Zolpidem and Zopiclone in Older Adults","authors":"Shih-Wei Lai,&nbsp;Kuan-Fu Liao","doi":"10.1002/hup.70038","DOIUrl":"10.1002/hup.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Zolpidem and zopiclone are widely prescribed hypnotics for older adults, yet their comparative safety regarding hip fracture risk remains unclear. This study aimed to compare the risk of hip fracture between zolpidem and zopiclone among adults aged 65–84 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Electronic health records from 166 global healthcare organizations in the TriNetX platform were analyzed. Adults aged 65–84 years who were newly prescribed zolpidem or zopiclone were identified. Propensity score matching was used to balance baseline characteristics. The TriNetX “Compare Outcomes” tool was used to estimate the cumulative incidence of hip fracture, hazard ratio, and 95% confidence interval between zolpidem users and zopiclone users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After propensity score matching, 41,500 adults were included in each group. During the 1-year follow-up period, 100 adults in the zolpidem group and 174 adults in the zopiclone group experienced a hip fracture, corresponding to cumulative incidences of 0.24% and 0.42%, respectively. In the Cox proportional hazards regression model, zolpidem use was associated with a reduced risk of hip fracture (hazard ratio 0.51; 95% confidence interval, 0.40–0.66).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Zolpidem was associated with a lower risk of hip fracture compared with zopiclone among adults aged 65–84 years. These findings highlight the need for further research to confirm these differences and explore underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583489","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":"Bupropion-Memantine Combination in the Treatment of Major Depressive Disorder and Treatment-Resistant Depression","authors":"Juan Miguel Riestra,&nbsp;Yaxel Levin-Carrion,&nbsp;Roshan Sutar,&nbsp;Jessica Mitchell,&nbsp;Pranav Jambulingam,&nbsp;Santiago J. Ballaz,&nbsp;Mujeeb U. Shad,&nbsp;Shafiqur Rahman,&nbsp;Stefano Barlati,&nbsp;Maju Mathew Koola","doi":"10.1002/hup.70039","DOIUrl":"10.1002/hup.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>Treatment-resistant depression (TRD) remains a formidable challenge in psychiatry, with nearly one-third of patients with major depressive disorder (MDD) failing to respond adequately to first-line pharmacological treatments. Pathophysiology in MDD has highlighted the N-methyl-D-aspartate (NMDA) glutamatergic system as a promising therapeutic target. In 2022, the US Food and Drug Administration (FDA) approved the bupropion and dextromethorphan (DXM) combination (BDC), the first oral combination that affects both the NMDA receptor and norepinephrine-dopamine systems. DXM is an uncompetitive NMDA receptor antagonist, and in combination with bupropion, it has been shown to be a rapidly acting oral medication with clinically significant improvement in the first week of treatment. BDC, however, has many inherent limitations such as contraindications in those with eating disorders and a history of seizures. Anxiety is a common comorbidity in MDD, and bupropion has been shown to lack efficacy in treating anxiety. In addition, BDC did not improve cognition. Memantine can treat depression and cognitive impairments concurrently. Fixed-dose combination pills can be less flexible than prescribing each drug separately, as BDC is limited to a 105 mg (bupropion)-45 mg (DXM) combination. The projected 1-month cost of possible combinations of memantine ($5.00) with a selective serotonin reuptake inhibitor (SSRI, $4.00), serotonin-norepinephrine reuptake inhibitor (SNRI, $15.00), and bupropion ($18.00) are cheaper than BDC ($1119.00). Instead of BDC, we propose various alternatives such as a bupropion-memantine combination or SSRI/SNRI and memantine for MDD/TRD.</p>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583541","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":"Developing a Polygenic Risk Score for Weight Gain in People Treated for Psychosis—Application in a Real-World Setting","authors":"Adrian Heald,&nbsp;Yasitha Illangasekera,&nbsp;Camila Marcelino Loureiro,&nbsp;Mark Shakespeare,&nbsp;Adam Jameson,&nbsp;Adrian Phillipson,&nbsp;Gavin P. Reynolds,&nbsp;Caroline Dalton","doi":"10.1002/hup.70035","DOIUrl":"10.1002/hup.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). Polygenic risk scores (PRS) could provide a measure of genetic predisposition to antipsychotic drug induced weight gain (AIWG).We conducted a study to examine how a PRS, generated using SNPs, identified from a recent meta-analysis, related to weight-change over time in people with first episode-psychosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The PRS included SNPs in six different genes, identified as having significant associations (<i>p</i> &lt; 0.05) with AIWG. These were <i>HTR2C</i> rs3813929; <i>MTHFR</i> rs1801133; <i>ADRA2A</i> rs1800544; <i>MC4R</i> rs489693; <i>LEPR</i> rs1137101 and <i>CNR1</i> rs1049353. An additive PRS and a risk allele based weighted PRS were created based on risk allele counts and presence or absence of risk alleles respectively. The additive PRS was also used to create low/high genetic risk groups for analysis. The association between PRS and weight gain per day (WGPD) in grams/day as well as BMI percentage change (=&gt; 7%) was investigated using regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In multiple regression analysis, the additive PRS significantly predicted AIWG in females (adjusted <i>r</i>² = 0.59, B: unstandardised regression coefficient = 24.4 g/day <i>p</i> &lt; 0.05), but not in males. ANCOVA showed that high genetic risk groups had greater WGPD (<i>p</i> = 0.018), with significant PRS gender interactions driven by markedly higher WGPD in high-risk females (<i>p</i> = 0.039). None of the models tested were associated with BMI percentage change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We report a PRS that is predictive of weight gain in women treated for first episode psychosis, accounting for 59% of the variance daily weight-gain over time. Validation in an independent cohort is required, as is determining whether it is feasible to apply the PRS prospectively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 2","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461468","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":"Clinical Potential of Mirtazapine in Anxiety and Trauma-Related Disorders: A Systematic Review and Meta-Analysis of Current Evidence","authors":"Claudio Caiazza,&nbsp;Vito Rago,&nbsp;Niccolò Solini,&nbsp;Luigi Franzese,&nbsp;Francesco Lusciano,&nbsp;Domenico Mazza,&nbsp;Claudia Rago","doi":"10.1002/hup.70037","DOIUrl":"10.1002/hup.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) with sedative features that may be advantageous for anxiety and trauma-related disorders, yet its role remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically reviewed and meta-analyzed the evidence on mirtazapine in anxiety disorders, major depressive disorder evaluating anxious symptoms, and trauma-related disorders, following PRISMA guidelines. Following a pre-registered protocol (https://osf.io/562zj/?view_only=0f596df97bc74b2bb25ebbf1dcbd7589), we searched PubMed/EMBASE/CENTRAL/ClinicalTrials.gov/WHO-ICTRP from inception until 07/07/2025. The co-primary outcomes were efficacy (symptom decrease—Standardized Mean Difference/SMD and response—Risk Ratio/RR) and acceptability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 799 identified records, 37 studies were included. In generalized anxiety disorder (GAD), mirtazapine paralleled selective serotonin reuptake inhibitors (SSRIs) (SMD = −0.14, 95% C.I. [−0.38, 0.09], <i>p</i> = 0.23, I² = 13.3%, <i>τ</i>² = 0.01, <i>k</i> = 5, <i>n</i> = 330), benzodiazepines (SMD = −0.03, 95% C.I. [−0.83, 0.77], <i>p</i> = 0.94, I² = 85.9%, <i>τ</i>² = 0.43, <i>k</i> = 4, <i>n</i> = 233). In major depressive disorder (MDD), mirtazapine slightly outperformed SSRIs regarding anxiety (SMD = −0.16, 95% C.I. [−0.25, 0.07], <i>p</i> &lt; 0.01, I² = 0%, <i>τ</i>² = 0, <i>k</i> = 10, <i>n</i> = 1732), and paralleled tricyclic antidepressants (TCAs). In post-traumatic stress disorder, SSRI augmentation was effective. Acceptability was comparable to placebo and SSRIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Mirtazapine was more effective than SSRIs for anxiety in MDD and may be preferred when anxiety is relevant. In GAD, mirtazapine may serve as an alternative to first-line agents, and further regulatory explorations are warranted. In PTSD, mirtazapine has potential as an augmentation strategy. Mirtazapine was generally well tolerated and may be advantageous for patients requiring rapid effect or relief from sleep disturbances.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 2","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438836","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":"Evaluation of Depression, Anxiety, and Sleep Quality in Patients With Acne Vulgaris Receiving Isotretinoin Treatment","authors":"Candan Celik,&nbsp;Mehmet Semih Celik","doi":"10.1002/hup.70036","DOIUrl":"10.1002/hup.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective</h3>\u0000 \u0000 <p>Isotretinoin is a systemic agent widely used in the treatment of severe acne vulgaris. Previous studies have reported that isotretinoin use may be associated with depression, anxiety, and sleep disorders. The aim of this study was to evaluate changes in sleep quality, anxiety, and depression in patients with acne vulgaris during isotretinoin treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective analysis of prospectively collected data included 155 patients receiving isotretinoin treatment at a tertiary dermatology outpatient clinic in Turkey between January 2023 and December 2024. The Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Global Acne Grading System (GAGS) were administered to patients before treatment, at the end of the first month, and at the end of the third month of treatment. Patients with a history of psychiatric disorders, use of psychotropic medications, or systemic diseases affecting sleep or mood were excluded from the study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Isotretinoin treatment was associated with a significant reduction in acne severity over the 3-month follow-up period. A transient increase in depressive and anxiety symptoms was observed during the first month of treatment, followed by a significant improvement by the third month. Overall, isotretinoin treatment was not associated with a significant deterioration in sleep quality throughout the study period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Isotretinoin treatment was associated with a significant reduction in acne severity, depression, and anxiety, while no significant overall change in sleep quality was observed. The temporary increase in depression and anxiety observed at the end of the first month may be related to the cutaneous side effects of isotretinoin. Further prospective studies are needed to better clarify the neuropsychiatric effects of isotretinoin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 2","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380520","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":"Medicines for Anxiety: A Hundred Years of Tranquillity and More to Come?","authors":"David Nutt","doi":"10.1002/hup.70034","DOIUrl":"https://doi.org/10.1002/hup.70034","url":null,"abstract":"&lt;p&gt;The modern use of medicines to treat anxiety began in the 1930s when barbiturates began to take over from bromide salts for tranquilisation on the grounds of improved tolerability [Glatt &lt;span&gt;1962&lt;/span&gt;]. Their use expanded after World War Two, often in combination with amphetamines (e.g., ‘Purple Hearts’), until in the 1960s concerns about their toxicity in accidental overdose (e.g., the case of the actress Marilyn Monroe) plus dependence, led to the search for safer alternatives. As a medical student in Guy's hospital in the early 1970s my interest in psychiatry was boosted by caring for several barbiturate-dependent patients undergoing withdrawal, and being intrigued by their florid hallucinations and delusions. Barbiturate replacements included methaqualone, glutethimide and clomethiazole, but these too had issues of overdose toxicity, dependence and withdrawal [Cowen and Nutt &lt;span&gt;1982&lt;/span&gt;]. In the early 1970s barbiturates were sufficiently commonly prescribed for a national campaign to stop them being instigated with the rather clever acronym CURB (Campaign to Use Restrict Barbiturates). This succeeded largely because much safer alternatives were becoming available in the 1960s - the benzodiazepines such as diazepam and chlordiazepoxide. These became the dominant anxiolytic (and hypnotic) medicines for the ensuing 3 decades because they were effective, generally well tolerated and it was virtually impossible to die from a benzodiazepine-alone overdose.&lt;/p&gt;&lt;p&gt;In parallel with the discovery of the benzodiazepines in the 1950s was a less obvious but eventually more significant development for anxiety treatments—the discovery of the monoamine oxidase inhibitors (MAOIs) such as phenelzine and the tricyclic antidepressants (TCAs) such as imipramine [see footnote]. Although the MAOIs were developed for depression, UK psychiatrists of the St Thomas' school of William Sargant observed they had powerful anti-phobic effects, for example they could treat agoraphobia [Sargant and Dally &lt;span&gt;1962&lt;/span&gt;]. However the (exaggerated) fear of toxicity of MAOIs, the need for dietary control (to avoid the tyramine ‘cheese’ reaction) plus their delayed onset of action made them much less easy to use than the benzodiazepines, which worked almost immediately. The use of MAOIs became limited to specialist centres whereas benzodiazepines became widely used especially in primary care.&lt;/p&gt;&lt;p&gt;Efficacy of TCAs for anxiety came in the early 1960s by Klein and Fink in the USA. Whilst exploring the efficacy of imipramine across several psychiatric disorders, and confirming its value in depression, they also noted a powerful effect on sudden anxiety attacks, but not on persistent worry [Klein and Fink &lt;span&gt;1962&lt;/span&gt;]. From this they suggested there were two types of anxiety: panic anxiety which responded to imipramine, and generalised anxiety which did not, but did respond to benzodiazepines. Despite hostile resistance by some UK ‘experts’ to this concept it h","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"41 2","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256493","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":"Comparison of Side Effects Between 3-Monthly and 1-Monthly Paliperidone Palmitate Formulations in Patients With Schizophrenia","authors":"Erkan Kuru,&nbsp;Ilker Ozdemir,&nbsp;Bengu Yucens,&nbsp;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}

{"title":"Pharmacological Management of Anxiety in End-of-Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin","authors":"Brunno Freitas da Costa,&nbsp;Paula Hartmann,&nbsp;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}

{"title":"Anxiolytic Medication Use in Low- Middle- and High-Income Countries: A World Mental Health Surveys Report","authors":"Dan J. Stein,&nbsp;Alan E. Kazdin,&nbsp;David S. Baldwin,&nbsp;Meredith G. Harris,&nbsp;Irving Hwang,&nbsp;Julia R. Pozuelo,&nbsp;Nancy A. Sampson,&nbsp;Peter Woodruff,&nbsp;Maria Carmen Viana,&nbsp;Sergio Aguilar-Gaxiola,&nbsp;Ali Al-Hamzawi,&nbsp;Jordi Alonso,&nbsp;Laura Helena Andrade,&nbsp;Corina Benjet,&nbsp;Ronny Bruffaerts,&nbsp;José-Miguel Caldas-de-Almeida,&nbsp;Stephanie Chardoul,&nbsp;Giovanni de Girolamo,&nbsp;Oye Gureje,&nbsp;Josep M. Haro,&nbsp;Elie G. Karam,&nbsp;Aimee Karam,&nbsp;Viviane Kovess-Masfety,&nbsp;Fernando Navarro-Mateu,&nbsp;Daisuke Nishi,&nbsp;José Posada-Villa,&nbsp;Annelieke Roest,&nbsp;Juan Carlos Stagnaro,&nbsp;Cristian Vladescu,&nbsp;Daniel V. Vigo,&nbsp;Ronald C. Kessler,&nbsp;the WHO World Mental Health Survey collaborators","doi":"10.1002/hup.70031","DOIUrl":"10.1002/hup.70031","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Face-to-face interviews with community samples totaling &lt;i&gt;n&lt;/i&gt; = 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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A weighted 5.6% (&lt;i&gt;n&lt;/i&gt; = 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&lt;sup&gt;2&lt;/sup&gt;&lt;sub&gt;1&lt;/sub&gt; = 559.6, &lt;i&gt;p&lt;/i&gt; &lt; 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 &lt;i&gt;very&lt;/i&gt; effective by 55.7% of users and &lt;i&gt;somewhat&lt;/i&gt; 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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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}