2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T431,A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes.31:Ta68,Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety. To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience. A systematic search was conducted using PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025. Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD. Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025. The primary outcomes were efficacy (ie, ≥50% reduction from baseline in the total Montgomery-Åsberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation). A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes. This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap.32:Tfed, Importance Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety. Objective To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience. Data Sources A systematic search was conducted using PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025. Study Selection Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD. Data Extraction and Synthesis Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025. Main Outcomes and Measures The primary outcomes were efficacy (ie, ≥50% reduction from baseline in the total Montgomery-Åsberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation). Results A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes. Conclusions and Relevance This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap. 33:T64b,Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field. To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use. With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.34:T774,Cholesterol is a vital molecule, especially during embryonic development. Disruption of the cholesterol biosynthetic pathway can arise from pathogenic genetic variants or exposure to prescription medications. We investigated the relationship between fifteen sterol biosynthesis inhibiting medications (SBIM) prescribed during pregnancy and the incidence of autism spectrum disorders (ASD) in the resulting offspring. Our study of the Epic Cosmos database queried linked child and maternal health records for births between 2014 and 2023 with follow-up to December 2025. The study included 6,135,213 children with linked maternal health records. We evaluated the incidence of ASD associated with maternal prescription of aripiprazole, atorvastatin, bupropion, buspirone, fluoxetine, haloperidol, metoprolol, nebivolol, pravastatin, propranolol, rosuvastatin, sertraline, simvastatin, and/or trazodone during pregnancy using Cox proportional hazard modeling. We found that exposure to at least one SBIM during pregnancy was associated with a 1.47-fold (95% CI 1.45-1.49) increased risk of an ASD after adjusting for potential confounders. For each additional SBIM co-prescribed, there was a 1.33 (95% CI 1.32-1.34) times increased risk of ASD, reaching 2.33-fold risk when 4 or more SBIMs were prescribed simultaneously. In the ten years of our cohort, we identified 234,971 (3.8%) children with an ASD diagnosis. Of the children with an ASD diagnosis, 35,152 (15.0%) of the mothers were prescribed at least one SBIM during pregnancy. Notably, in our dataset, utilization of SBIM medications by pregnant women increased from 4.6% in 2014 to16.8% in 2023. In conclusion, SBIMs may be potentially harmful to the developing fetus. Given that these drugs account for over 400 million prescriptions annually in the U.S. we recommend these findings be considered before prescribing SBIM medications during pregnancy.35:T4c8,Mounting evidence supports the efficacy of nonpharmacologic or psychosocial interventions for reducing behavioral and psychological symptoms of dementia (BPSD), identifies the comparative risks and benefits of psychotropic medication, and underscores the importance of deprescribing psychotropic medications. However, evidence from clinical settings indicates that uptake of nonpharmacologic interventions and potential overuse of medications remain problematic. We begin by discussing the importance of exploring potential contributors to BPSD, using person-centered language to describe BPSD, implementing holistic and person-centered care plans, measuring clinically important changes in BPSD, and considering social determinants of health when assessing and managing BPSD; we also discuss the historical context informing how clinicians manage BPSD. Next, we compare and contrast nonpharmacologic and pharmacologic approaches to managing BPSD, evaluate their individual and comparative efficacy, and describe recommendations for intervention deprescribing or deimplementation. Lastly, we discuss strengths and limitations of the current evidence supporting BPSD management as well as recommendations for future research.36:T4d9,Mounting evidence supports the efficacy of nonpharmacologic or psychosocial interventions for reducing behavioral and psychological symptoms of dementia (BPSD), identifies the comparative risks and benefits of psychotropic medication, and underscores the importance of deprescribing psychotropic medications. However, evidence from clinical settings indicates that uptake of nonpharmacologic interventions and potential overuse of medications remain problematic. We begin by discussing the importance of exploring potential contributors to BPSD, using person-centered language to describe BPSD, implementing holistic and person-centered care plans, measuring clinically important changes in BPSD, and considering social determinants of health when assessing and managing BPSD; we also discuss the historical context informing how clinicians manage BPSD. Next, we compare and contrast nonpharmacologic and pharmacologic approaches to managing BPSD, evaluate their individual and comparative efficacy, and describe recommendations for intervention deprescribing or deimplementation. Lastly, we discuss strengths and limitations of the current evidence supporting BPSD management as well as recommendations for future research.37:T632,This case report presents the comprehensive, multidisciplinary treatment of a 17-year-old male adolescent diagnosed with avoidant/restrictive food intake disorder (ARFID) in Turkiye. The patient developed severe food avoidance, vomiting, and significant weight loss after experiencing traumatic medical interventions, including nasogastric tube placement. His clinical course was further complicated by medical comorbidities such as achalasia, superior mesenteric artery syndrome, and gallstones, which contributed to persistent gastrointestinal discomfort and reinforced his restrictive eating behaviors. Treatment combined with outpatient Cognitive Behavioral Therapy for ARFID (CBT-AR), psychopharmacological support, family-based interventions, and ongoing medical management. CBT-AR was flexibly adapted to address the patient's fear of negative eating consequences, sensory sensitivities, and low appetite, while considering family dynamics and culturally relevant eating practices. Over a 12-month period, the patient's weight increased from 42.6 kg to 55 kg, his dietary variety expanded with the addition of 38 new foods, and his ARFID symptoms showed significant clinical improvement. This is the first documented case of CBT-AR applied in Turkiye, highlighting the feasibility and effectiveness of a combined medical-psychological approach for complex ARFID presentations. The case underscores the necessity of individualized, culturally sensitive treatment strategies and multidisciplinary collaboration in addressing ARFID, particularly in medically compromised patients.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Atypical Antipsychotic: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Atypical Antipsychotic (modality). Clinician-written summaries and actionable practice insights. 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this is consistent with the paper's publication date but is a very recent regulatory event that clinicians should verify against current labelling.","value_numeric":null},{"paper_doi":"10.1038/s41582-026-01260-5","tag_type":"warning","value":"Full text was behind a paywall; structured data are drawn from the abstract, key points, and reference list only — specific effect sizes and trial-level numbers could not be verified.","value_numeric":null},{"paper_doi":"10.1038/s41582-026-01260-5","tag_type":"warning","value":"Study design is described as a 'Review Article' in the publisher metadata; classified here as a Narrative Review rather than Systematic Review, as no formal PRISMA or systematic search methodology is described.","value_numeric":null},{"paper_doi":"10.1038/s41582-026-01260-5","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the integration of new FDA-approved agents and biomarker-guided prescribing recommendations, but the underlying evidence base for several emerging agents remains early-phase or post hoc.","value_numeric":null}],"summaries":{"what_studied":"This review synthesizes evidence for pharmacological and non-pharmacological symptomatic therapies in Alzheimer disease (AD), covering cognition, function, and neuropsychiatric symptoms, including established agents (cholinesterase inhibitors, memantine), emerging drugs (brexpiprazole, pimavanserin, muscarinic agonists), and non-drug approaches (cognitive training, physical exercise, cognitive stimulation therapy, multimodal lifestyle programmes).","key_result":"Cholinesterase inhibitors and memantine provide modest but significant cognitive and functional benefits, with biomarker-stratified data suggesting greater benefit in confirmed AD pathology. Non-pharmacological interventions show small-to-moderate effects, strongest for cognitive training and structured exercise in mild cognitive impairment. For neuropsychiatric symptoms, personalized psychosocial interventions meaningfully reduce agitation and depression; brexpiprazole and pimavanserin offer incremental gains over atypical antipsychotics but with more favourable safety profiles.","limitations":"- Full text was not accessible; summary is based on abstract, key points, and reference list only, limiting depth of critical appraisal.\n- As a narrative review, it does not perform a de novo meta-analysis and may be subject to selective citation.\n- Biomarker-stratified analyses referenced are largely post hoc or observational, limiting causal inference about precision prescribing.","practice_takeaway":"Continue cholinesterase inhibitors and memantine as first-line symptomatic therapy, prioritising patients with confirmed AD biomarkers. For agitation, try personalized psychosocial approaches first; if pharmacotherapy is needed, brexpiprazole is now FDA-approved as a non-antipsychotic option with a more favourable safety profile than older atypical antipsychotics."}},{"doi":"10.1192/bjp.2026.10726","pmid":"42661560","title":"Incidence of clozapine-associated neutropenia in patients with schizophrenia: 20-year population-based study in Hong Kong","journal_title":"The British Journal of Psychiatry","journal_issn":"0007-1250","published_at":"2026-08-28T00:00:00.000Z","url":"https://doi.org/10.1192/bjp.2026.10726","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-05T06:20:17.332Z","updated_at":"2026-09-05T06:20:17.332Z","tags":[{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"brand","value":"Clozaril","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"condition","value":"Clozapine-Associated Neutropenia","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"condition","value":"Treatment-Resistant Schizophrenia","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"generic","value":"clozapine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"modality","value":"Second-Generation Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"sample_size","value":"n=43145","value_numeric":43145},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"warning","value":"Benign ethnic neutropenia (BEN) could not be systematically excluded, though authors note it is likely rare in Chinese populations.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"warning","value":"Non-clozapine SGAs were treated as a single comparator group; individual drug-level neutropenia risk differences were not analyzed.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"warning","value":"The brand tag 'Clozaril' is the most common proprietary name for clozapine but was not explicitly mentioned in the paper; it is inferred from the generic drug name.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10726","tag_type":"warning","value":"The study population is predominantly Chinese/Asian (Hong Kong), limiting direct generalisability to Western or ethnically diverse populations, particularly given known lower rates of clozapine-induced agranulocytosis in Asian cohorts.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study compared neutropenia risk in 4,868 incident clozapine users versus 38,277 non-clozapine SGA users with schizophrenia drawn from Hong Kong electronic health records (2003–2019), with follow-up to 2023 (median 8.84 years).","key_result":"Clozapine carried significantly higher risk of minor (IRR 5.91; 95% CI 3.96–8.70) and serious neutropenia (IRR 3.48; 95% CI 1.70–6.84) only in the first 18 weeks; adjusted overall rates of serious neutropenia were virtually identical (0.37 vs. 0.36 per 100 person-years). Risk converged with non-clozapine SGAs by ~2 years (82–135 weeks). Patients ≥45 years drove the early serious neutropenia signal; those <45 showed no significant excess early risk.","limitations":"- Surveillance bias is likely: non-clozapine SGA users had less frequent blood monitoring, potentially underestimating neutropenia incidence in that group.\n- Non-clozapine SGAs were analysed as a single class, ignoring varied neutropenic risk among individual drugs.\n- Medication adherence could not be verified from prescription records alone.","practice_takeaway":"Weekly ANC monitoring for the first 18 weeks of clozapine, then monthly until 2 years, appears sufficient — after which frequency can match that used for other SGAs. Clinicians may also consider age-based tailoring: patients ≥45 years face the highest early serious neutropenia risk, while those <45 may not need the same intensity of early monitoring."}},{"doi":"10.1136/bmj-2026-100216","pmid":"42580772","title":"Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-08-11T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-100216","source_score":89,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:30.432Z","updated_at":"2026-08-17T13:33:30.432Z","tags":[{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Caplyta","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Latuda","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Vraylar","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"asenapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"cariprazine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"divalproex","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"fluoxetine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"haloperidol","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lumateperone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ziprasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Brain Stimulation","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Mood Stabilizer","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Psychosocial Intervention","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sample_size","value":"n=77","value_numeric":77},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"study_design","value":"Umbrella Review (Living Systematic Review with Meta-Analyses)","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Study design label 'Umbrella Review' is a non-standard design category; it is a higher-order synthesis above standard systematic reviews and meta-analyses.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Tamoxifen is listed as effective for adult mania — this is an uncommon clinical use (PKC inhibition mechanism) and may surprise readers unfamiliar with this evidence base.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because this is a comprehensive living umbrella review with an open-access clinical decision tool, though individual treatment effect sizes are not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The sample_size tag reflects the number of included systematic reviews (n=77), not individual patient-level N, which is not reported as a single aggregate in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A living umbrella review (U-REACH) evaluated the certainty of evidence for pharmacological, nutraceutical, psychosocial, brain stimulation, and circadian rhythm-based treatments across all bipolar disorder phases (depression, mania/mixed, maintenance) and age groups (adults; children/adolescents), using 77 systematic reviews (21 network meta-analyses, 56 pairwise meta-analyses) published up to November 2024.","key_result":"Across 2,510 meta-analyses covering 133 outcomes and 116 unique treatments, GRADE ratings were high (n=236), moderate (n=827), low (n=986), and very low (n=461). Agents effective across multiple phases in adults included aripiprazole, asenapine, cariprazine, divalproex/valproate, lamotrigine, lithium, olanzapine, paliperidone, quetiapine, and risperidone; in youth, lurasidone and olanzapine-fluoxetine were supported for bipolar depression, and aripiprazole, asenapine, olanzapine, quetiapine, and risperidone for mania.","limitations":"Most evidence is rated low or very low certainty (1,447 of 2,510 meta-analyses), limiting confidence in many treatment estimates; the umbrella review design inherits limitations of the included meta-analyses (e.g., heterogeneity, publication bias); pediatric data are sparse compared with adult data.","practice_takeaway":"Use the freely available EBI-BD platform (ebibd-database.org) to identify phase- and age-specific evidence-based options and discuss patient-preferred safety profiles using its 12-intervention, 17-outcome preference tool. For cross-phase adult coverage, lithium, quetiapine, olanzapine, aripiprazole, and divalproex/valproate have the broadest support; for youth, lurasidone (bipolar depression) and aripiprazole (mania) have the strongest pediatric evidence."}},{"doi":"10.1097/yic.0000000000000613","pmid":"41609240","title":"An observational study on the effects of as-needed use of various antipsychotic drugs for agitation due to psychotic disorders","journal_title":"International Clinical Psychopharmacology","journal_issn":"0268-1315","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1097/yic.0000000000000613","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-04T13:23:43.406Z","updated_at":"2026-06-04T13:23:43.406Z","tags":[{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"brand","value":"Saphris","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"condition","value":"Acute Psychotic Agitation","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"condition","value":"Schizophrenia","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"generic","value":"asenapine","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"generic","value":"haloperidol","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"modality","value":"Typical Antipsychotic","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"sample_size","value":"n=170","value_numeric":170},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"study_design","value":"Prospective Observational Study","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"warning","value":"Brand tag 'Saphris' is included for asenapine; note that availability and brand names vary by region.","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"warning","value":"Direct comparison between oral/sublingual and injectable agents is not appropriate due to major baseline differences in patient cooperativeness (medication refusal 4.3% vs. 65.5%) — the authors explicitly note this.","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"warning","value":"Planned sample size (~307) was not achieved; several drug subgroups are small, limiting statistical power for between-drug comparisons.","value_numeric":null},{"paper_doi":"10.1097/yic.0000000000000613","tag_type":"warning","value":"Study was conducted exclusively in Japanese psychiatric emergency wards; findings may not generalize to other healthcare systems or settings where different agents (e.g., benzodiazepines, loxapine) are standard.","value_numeric":null}],"summaries":{"what_studied":"This 6-month multicenter naturalistic observational study compared time to calming (ACES = 3) after PRN antipsychotic use in 170 newly admitted adults with acute psychotic disorders and moderate-to-marked agitation, across 7 oral/sublingual and injectable agents.","key_result":"Mean onset of calming: asenapine-SL 30.0 min, olanzapine-ODT 31.9 min, risperidone-OS 34.5 min, quetiapine 46.6 min; olanzapine-IM 36.3 min, haloperidol-IM 47.5 min, haloperidol-IV 45.0 min. Quetiapine had a significantly lower hazard of achieving calming vs. asenapine-SL (HR 0.39; 95% CI 0.20–0.78; P=0.007). No significant differences among injectables. Medication refusal was far more common with injectables (65.5% vs. 4.3% for oral/SL).","limitations":"- Nonrandomized design with likely confounding by indication; sicker, less cooperative patients tended to receive injectables, making cross-route comparisons unreliable.\n- Did not reach planned sample size; small subgroups (e.g., olanzapine-ODT, haloperidol-IV) limit precision.\n- Fixed 15-min assessment intervals may have missed earlier calming onsets; no centralized ACES rater training.","practice_takeaway":"For cooperative patients with acute psychotic agitation, sublingual asenapine and olanzapine-ODT appear to produce calming in about 30 minutes — comparable to IM agents — and may be preferred when patients can accept oral/SL dosing. A structured PRN reassessment at 30–45 minutes is reasonable for most antipsychotic routes."}},{"doi":"10.1007/s00787-026-03049-9","pmid":"42149225","title":"Systematic review: Efficacy of off-label antipsychotic use in children and adolescents with obsessive-compulsive, mood dysregulation, depression, anxiety, and sleep-related disorders","journal_title":"European Child & Adolescent Psychiatry","journal_issn":"1018-8827","published_at":"2026-05-18T00:00:00.000Z","url":"https://doi.org/10.1007/s00787-026-03049-9","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-22T13:22:19.207Z","updated_at":"2026-05-22T13:22:19.207Z","tags":[{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"category","value":"Pediatrics","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Anxiety Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Borderline Personality Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Disruptive Mood Dysregulation Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Obsessive-Compulsive Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"condition","value":"Sleep Disorder","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"amisulpride","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"clozapine","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"sample_size","value":"n=241","value_numeric":241},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"warning","value":"Age range spans 6–18 years with likely inclusion of one 18-year-old; the review is predominantly but not exclusively under-18.","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"warning","value":"Level of evidence tag set to '3' reflecting systematic review methodology, but the review itself found only very low quality (GRADE) primary studies — the overall evidence base is effectively much weaker than the review design level implies.","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"warning","value":"No studies on anxiety or sleep disorders were identified, so tags for these conditions reflect intended scope rather than included data.","value_numeric":null},{"paper_doi":"10.1007/s00787-026-03049-9","tag_type":"warning","value":"Total sample size of n=241 is an approximation summing patients across OCD (137), mood dysregulation (91), and depression (13) categories; some patients from overlapping Masi et al. studies may have been counted twice.","value_numeric":null}],"summaries":{"what_studied":"This systematic review assessed the efficacy of off-label antipsychotic use in children and adolescents (<18 years) for OCD, mood dysregulation, depression, anxiety, and sleep disorders, searching MEDLINE, EBM Reviews, and PsycINFO through October 2025 and evaluating evidence using GRADE.","key_result":"Of 2,237 screened studies, only 13 met inclusion criteria (5 on OCD, 6 on mood dysregulation/borderline disorders, 2–3 on depression; total patients: OCD n=137, mood dysregulation n=91, depression n=13). All 13 studies rated **very low** certainty of evidence by GRADE — no RCTs, no studies on anxiety or sleep disorders were found. Standardized mean score changes ranged from 0.5–1.8 (OCD) and 0.6–1.4 (mood dysregulation), but without control arms these are uninterpretable.","limitations":"- All 13 included studies were uncontrolled (case series, open-label trials, one case report); no placebo-controlled or randomized trials existed.\n- Small sample sizes, heterogeneous comorbidities, concomitant medications, and variable outcome measures prevented meta-analysis or publication bias assessment.\n- Only English-language studies were included, raising risk of language bias.","practice_takeaway":"There is no reliable evidence to support off-label antipsychotic prescribing for OCD, mood dysregulation, depression, anxiety, or sleep disorders in children and adolescents — yet use is rising sharply. Clinicians should carefully weigh known metabolic, cardiovascular, and neurological risks against unproven benefits before prescribing antipsychotics off-label in this age group."}},{"doi":"10.1001/jamapsychiatry.2026.0658","pmid":"42090141","title":"Adjunctive Antipsychotics in Major Depressive Disorder","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-05-06T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13150735/","source_score":88,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1001/jamapsychiatry.2026.0658","days":"7","issn":"2168-622X","rank":"8","field":"Clinical Medicine","score":"88","category":"Psychiatry","categories":["Psychiatry"],"_categories":["Psychiatry"]},"pubmed":{"doi":"10.1001/jamapsychiatry.2026.0658","title":"Adjunctive Antipsychotics in Major Depressive Disorder: A Systematic Review and Network Meta-Analysis.","journal":"JAMA psychiatry","methods":"","results":"$30","abstract":"$31","keywords":[],"pubmed_id":"42090141","conclusions":"","publication_date":"2026-05-06T00:00:00"},"crossref":{"DOI":"10.1001/jamapsychiatry.2026.0658","URL":"https://doi.org/10.1001/jamapsychiatry.2026.0658","ISSN":["2168-622X"],"link":[{"URL":"https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2848529/jamapsychiatry_mcintyre_2026_oi_260019_1777303646.00799.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Adjunctive Antipsychotics in Major Depressive Disorder"],"author":[{"given":"Roger S.","family":"McIntyre","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Stephen M.","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience, University of California, Riverside"}]},{"given":"Sung Ryul","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea"}]},{"given":"Maurizio","family":"Pompili","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy"}]},{"given":"Joseph F.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York"},{"name":"Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York"},{"name":"Charité–Universitätsmedizin Berlin, Berlin, Germany"}]},{"given":"Angela T. 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Aripiprazole had the best acceptability profile (RR 1.16; 95% CrI 0.89–1.50) with strong efficacy (RR 1.53; 95% CrI 1.32–1.77). Quetiapine XR's efficacy did not reach statistical significance (RR 1.15; 95% CrI 0.96–1.35).","limitations":"- Only short-term studies included; no adequate long-term maintenance data exist for any agent.\n- Lumateperone had the smallest sample size (n=483), which may inflate its effect estimate.\n- All trials were industry-sponsored, raising potential risk of bias.","practice_takeaway":"When choosing an adjunctive antipsychotic for MDD, aripiprazole offers the best balance of efficacy and tolerability; lumateperone shows the highest response rate but carries the greatest discontinuation risk. Quetiapine XR's efficacy advantage over placebo was not statistically significant in this analysis."}},{"doi":"10.1370/afm.250266","pmid":"42055743","title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation","journal_title":"The Annals of Family Medicine","journal_issn":"1544-1709","published_at":"2026-04-30T00:00:00.000Z","url":"https://doi.org/10.1370/afm.250266","source_score":79,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-04","doi":"10.1370/afm.250266","days":"14","issn":"1544-1709","rank":"1","field":"Clinical Medicine","score":"79","category":"Primary Health Care","categories":["Primary Health Care"],"_categories":["Primary Health Care"]},"pubmed":{"doi":"10.1370/afm.250266","title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.","journal":"Annals of family medicine","methods":"","results":"With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B","abstract":"$33","keywords":["chronic fatigue syndrome","chronic illness","clinical practice patterns","complementary therapies","integrative medicine","long COVID","medications","myalgic encephalomyelitis","pharmacotherapy","practice-based research","primary care","specialists","supplements"],"pubmed_id":"42055743","conclusions":"Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.","publication_date":"2026-04-30T00:00:00"},"crossref":{"DOI":"10.1370/afm.250266","URL":"https://doi.org/10.1370/afm.250266","ISSN":["1544-1709","1544-1717"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1370/afm.250266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"250266","type":"journal-article","issue":null,"score":1,"title":["Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation"],"author":[{"given":"Stephanie L.","family":"Grach","sequence":"first","affiliation":[]},{"given":"Jaime","family":"Seltzer","sequence":"additional","affiliation":[]},{"given":"Michael R.","family":"Mueller","sequence":"additional","affiliation":[]},{"given":"Chris 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T.","family":"Hurt","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,4,29]]},"member":"1","prefix":"10.1370","source":"Crossref","volume":null,"created":{"date-time":"2026-04-29T14:40:13Z","timestamp":1777473613000,"date-parts":[[2026,4,29]]},"indexed":{"date-time":"2026-05-02T23:03:52Z","timestamp":1777763032854,"date-parts":[[2026,5,2]]},"subject":[],"abstract":null,"accepted":{"date-parts":[[2026,2,3]]},"language":"en","relation":{},"resource":{"primary":{"URL":"http://www.annfammed.org/lookup/doi/10.1370/afm.250266"}},"subtitle":[],"deposited":{"date-time":"2026-04-29T14:40:14Z","timestamp":1777473614000,"date-parts":[[2026,4,29]]},"issn-type":[{"type":"print","value":"1544-1709"},{"type":"electronic","value":"1544-1717"}],"published":{"date-parts":[[2026,4,29]]},"publisher":"Annals of Family Medicine","reference":null,"short-title":[],"alternative-id":["10.1370/afm.250266"],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["The Annals of Family Medicine"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,4,29]]},"references-count":0,"short-container-title":["Ann Fam Med"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1370/afm.250266","is_oa":true,"title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist 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Syndrome","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"amitriptyline","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"duloxetine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"fludrocortisone","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"gabapentin","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"guanfacine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"midodrine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"montelukast","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"naltrexone","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"pyridostigmine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Acetylcholinesterase Inhibitor","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Gabapentinoid","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Opioid Antagonist (Low-Dose)","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Serotonin-Norepinephrine Reuptake Inhibitor","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Tricyclic Antidepressant","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"sample_size","value":"n=571","value_numeric":571},{"paper_doi":"10.1370/afm.250266","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"Fibromyalgia patients were excluded to reduce confounding, which may limit applicability to the many ME/CFS patients who have co-occurring fibromyalgia.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"Supplement and medication data relied on patient self-report from intake forms without dose or indication details, introducing possible recall and documentation bias.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"The cohort is 91.4% non-Hispanic White from one U.S. academic center; findings may not reflect prescribing patterns in more diverse or non-academic settings.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"The 'practice_changing' impact flag reflects a significant gap between specialist and generalist prescribing, but this is a single-center retrospective study—causality and generalizability are limited.","value_numeric":null}],"summaries":{"what_studied":"A retrospective cohort study of 571 adults (age 18–70) with ME/CFS—without co-diagnosis of fibromyalgia—referred to a Mayo Clinic specialty clinic in Minnesota (2018–2022), examining which medications and supplements had already been tried before their first specialist consultation.","key_result":"Only 68.3% of patients had tried at least 1 medication potentially targeting ME/CFS symptoms (mean 1.5 medications per patient). Medications most often prescribed were SNRIs (182 patients), gabapentin (155), and tricyclic antidepressants (134)—primarily pain/mood agents—while specialist-favored drugs for fatigue, brain fog, and orthostatic intolerance were rarely used: low-dose naltrexone (8 patients), aripiprazole (12), pyridostigmine (4), midodrine (7). Meanwhile, 72.2% used at least 1 dietary supplement, most commonly vitamin D (359 patients), vitamin B12/B complex (72), and fish oil (51).","limitations":"- Dosages, duration, and reasons for use/discontinuation were not captured, so it is unknown whether medications were prescribed at ME/CFS-appropriate doses.\n- Cohort was predominantly non-Hispanic White (91.4%) from a single specialty clinic, limiting generalizability.\n- Study period ended in 2022; prescribing patterns may have shifted since then, and pediatric/geriatric patients were excluded.","practice_takeaway":"Most ME/CFS patients arrive at specialist care having tried only pain- and mood-targeted drugs, while evidence-informed options for fatigue, orthostatic intolerance, and brain fog (e.g., low-dose naltrexone, aripiprazole, pyridostigmine, guanfacine) are rarely prescribed by generalists. Primary care clinicians should familiarize themselves with ME/CFS treatment guides and use a 'start low, go slow' approach when initiating these agents."}},{"doi":"10.1038/s41380-026-03610-7","pmid":"41991716","title":"Sterol pathway disruption in pregnancy: a link to autism","journal_title":"Molecular Psychiatry","journal_issn":"1359-4184","published_at":"2026-04-17T00:00:00.000Z","url":"https://doi.org/10.1038/s41380-026-03610-7","source_score":153,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-17","doi":"10.1038/s41380-026-03610-7","days":"30","issn":"1359-4184","rank":"10","field":"Clinical Medicine","score":"153","category":"Psychiatry","categories":["Psychiatry"],"_categories":["Psychiatry"]},"pubmed":{"doi":"10.1038/s41380-026-03610-7","title":"Sterol pathway disruption in pregnancy: a link to autism.","journal":"Molecular psychiatry","methods":"","results":"","abstract":"$34","keywords":[],"pubmed_id":"41991716","conclusions":"","publication_date":"2026-04-17T00:00:00"},"crossref":{"DOI":"10.1038/s41380-026-03610-7","URL":"https://doi.org/10.1038/s41380-026-03610-7","ISSN":["1359-4184","1476-5578"],"link":[{"URL":"https://www.nature.com/articles/s41380-026-03610-7.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41380-026-03610-7","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41380-026-03610-7.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Sterol pathway disruption in pregnancy: a link to autism"],"author":[{"given":"Eric S.","family":"Peeples","sequence":"first","affiliation":[]},{"given":"A. 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The study adjusts for confounders but cannot fully exclude this bias.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03610-7","tag_type":"warning","value":"Cox proportional hazard modeling was used, but the study does not specify whether individual drugs were analyzed separately; pooled SBIM class effects may mask heterogeneity across very different drug classes.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03610-7","tag_type":"warning","value":"The abstract lists 14 drug names despite claiming 15 SBIMs — one medication may be missing from the abstract text.","value_numeric":null}],"summaries":{"what_studied":"This large retrospective cohort study examined whether maternal prescription of 15 sterol biosynthesis inhibiting medications (SBIMs) during pregnancy was associated with autism spectrum disorder (ASD) in offspring, using the Epic Cosmos database covering 6.1 million children born 2014–2023 with follow-up through December 2025.","key_result":"Exposure to ≥1 SBIM during pregnancy was associated with a 1.47-fold increased risk of ASD (95% CI 1.45–1.49); each additional co-prescribed SBIM added a 1.33× risk multiplier, reaching 2.33-fold risk with ≥4 simultaneous SBIMs. Of 234,971 children (3.8%) diagnosed with ASD, 15.0% of their mothers had been prescribed ≥1 SBIM in pregnancy.","limitations":"Observational design cannot establish causation; residual confounding by indication (e.g., maternal psychiatric or metabolic conditions driving both SBIM use and ASD risk) is a major concern. ASD diagnosis relied on health records, which may miss undiagnosed cases or reflect detection bias. Specific SBIM dose, timing, and duration during pregnancy were not individually analyzed.","practice_takeaway":"Clinicians prescribing SBIMs (e.g., statins, SSRIs, antipsychotics, beta-blockers) to pregnant patients should weigh this signal of elevated ASD risk—especially with multiple co-prescribed SBIMs—against the benefits of treatment. These findings warrant prospective investigation before practice-changing decisions, but the dose-response pattern strengthens the biological plausibility."}},{"doi":"10.1001/jamapsychiatry.2026.0086","pmid":"41811299","title":"Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-03-11T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12980359/","source_score":89,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:23:49.468Z","updated_at":"2026-06-10T14:23:49.468Z","tags":[{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"condition","value":"First-Episode Psychosis","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"condition","value":"Schizoaffective Disorder","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"condition","value":"Schizophrenia","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"condition","value":"Schizophreniform Disorder","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"amisulpride","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"clozapine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"perphenazine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"modality","value":"Typical Antipsychotic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"sample_size","value":"n=654","value_numeric":654},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"warning","value":"Phase 2 clozapine arm had only 32 participants — results should be interpreted with caution due to small subgroup size.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"warning","value":"The study used a sequential re-randomization design (not a simple parallel RCT), which may affect how level of evidence is interpreted.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"warning","value":"The trial was conducted exclusively in China; applicability to non-Chinese populations is uncertain.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0086","tag_type":"warning","value":"Time to all-cause discontinuation was listed as a co-primary outcome but results for this endpoint were not reported in the provided abstract or results sections.","value_numeric":null}],"summaries":{"what_studied":"A sequential, assessor-blind RCT across 7 centers in China (Feb 2019–Oct 2022) evaluated whether switching to clozapine outperforms other antipsychotics in first-episode psychosis (FEP) patients aged 16–45 who failed one 8-week antipsychotic trial (olanzapine, risperidone, amisulpride, aripiprazole, or perphenazine). Phase 2 nonresponders were rerandomized to olanzapine, amisulpride, or clozapine for another 8 weeks.","key_result":"In phase 1 (n=654), overall response rate was 55.1%; risperidone (63.4%) and amisulpride (61.8%) outperformed aripiprazole (44.3%) and perphenazine (45.7%) (p=0.001). In phase 2 (n=111 nonresponders), clozapine achieved a ≥40% PANSS reduction in **62.5%** of patients vs 44.7% on amisulpride and 31.7% on olanzapine (p=0.03).","limitations":"- Phase 2 was underpowered with only 111 rerandomized participants (32 on clozapine), limiting precision of comparisons.\n- Single-country (China) multicenter design may limit generalizability to other populations.\n- The 8-week phase 2 window is short; long-term clozapine efficacy and safety beyond this period were not formally assessed in the trial.","practice_takeaway":"For FEP patients who fail one adequate antipsychotic trial, consider early clozapine use — it produced a response in nearly two-thirds of phase 2 nonresponders, nearly double the rate seen with olanzapine. Risperidone or amisulpride may be preferred as first-line agents given their higher phase 1 response rates."}},{"doi":"10.1146/annurev-clinpsy-061724-085912","pmid":"41678258","title":"Management of Behavioral and Psychological Symptoms of Dementia: Nonpharmacologic and Pharmacologic Interventions","journal_title":"Annual Review of Clinical Psychology","journal_issn":"1548-5943","published_at":"2026-02-12T00:00:00.000Z","url":"https://doi.org/10.1146/annurev-clinpsy-061724-085912","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.1146/annurev-clinpsy-061724-085912","days":"7","issn":"1548-5943","rank":"7","field":"Clinical Medicine","score":"12","category":"Psychology, Clinical","categories":["Psychology, Clinical"],"_categories":["Psychology, Clinical"]},"pubmed":{"doi":"10.1146/annurev-clinpsy-061724-085912","title":"Management of Behavioral and Psychological Symptoms of Dementia: Nonpharmacologic and Pharmacologic Interventions.","journal":"Annual review of clinical psychology","methods":"","results":"","abstract":"$35","keywords":["behavioral and psychological symptoms of dementia","behavioral symptoms","dementia","patient-centered care"],"pubmed_id":"41678258","conclusions":"","publication_date":"2026-02-12T00:00:00"},"crossref":{"DOI":"10.1146/annurev-clinpsy-061724-085912","URL":"https://doi.org/10.1146/annurev-clinpsy-061724-085912","ISSN":["1548-5943","1548-5951"],"link":[{"URL":"https://www.annualreviews.org/content/journals/10.1146/annurev-clinpsy-061724-085912?crawler=true&mimetype=application/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"397-425","type":"journal-article","issue":"1","score":1,"title":["Management of Behavioral and Psychological Symptoms of Dementia: Nonpharmacologic and Pharmacologic Interventions"],"author":[{"given":"Jennifer A.","family":"Watt","sequence":"first","affiliation":[{"name":"1Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"2Division of Geriatric Medicine, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; email: jennifer.watt@utoronto.ca"},{"name":"3Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"4Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"5O'Brien Institute of Public Health, University of Calgary, Calgary, Alberta, Canada"},{"name":"6Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada"}]},{"given":"Natasha","family":"Lane","sequence":"additional","affiliation":[{"name":"7Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"8Edwin S.H. 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The summary reflects the guideline content as extracted.","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"warning","value":"The guideline was approved in February 2016 with a 5-year validity window; it may be substantially outdated relative to current evidence as of 2026.","value_numeric":null}],"summaries":{"what_studied":"This is an Australian national clinical practice guideline (adapted from the UK NICE guideline via the ADAPTE process) covering the diagnosis and management of dementia across community, residential, and hospital settings. It addresses assessment, pharmacological and nonpharmacological BPSD management, carer support, and palliative care, with evidence graded using GRADE methodology.","key_result":"Nonpharmacological approaches (multicomponent, music, massage, reminiscence, behavioral management) are recommended first-line for BPSD. Antipsychotics should generally be avoided in mild-to-moderate BPSD due to increased risk of cerebrovascular events and death (3.5% vs 2.3% placebo mortality in meta-analysis of 15 trials; OR 1.54). SSRIs — especially citalopram — showed significant benefit for agitation in two large RCTs. AChEIs showed small but significant benefits on cognition and ADL in mild-to-severe Alzheimer's disease and other dementia subtypes.","limitations":"Evidence base is largely low-to-very-low GRADE quality for nonpharmacological interventions. The guideline was adapted for Australia in 2016 from a 2006 UK source and may not reflect current evidence. Few economic evaluations were conducted in Australian settings.","practice_takeaway":"Try nonpharmacological strategies first for BPSD — music, massage, behavioral management, and multicomponent programs have the best evidence. Reserve antipsychotics for severe psychosis or agitation causing significant distress, use the lowest effective dose, reassess every 4–12 weeks, and actively deprescribe when possible."}},{"doi":"10.1186/s40337-025-01463-z","pmid":"41420189","title":"Integrating cognitive-behavioral and medical interventions for ARFID in an adolescent: a case report from Turkiye","journal_title":"Journal of Eating Disorders","journal_issn":"2050-2974","published_at":"2025-12-20T00:00:00.000Z","url":"https://doi.org/10.1186/s40337-025-01463-z","source_score":18,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-25","doi":"10.1186/s40337-025-01463-z","days":"30","issn":"2050-2974","rank":"9","field":"Clinical Medicine","score":"18","category":"Psychology, Clinical","categories":["Psychology, Clinical"],"_categories":["Psychology, Clinical"]},"pubmed":{"doi":"10.1186/s40337-025-01463-z","title":"Integrating cognitive-behavioral and medical interventions for ARFID in an adolescent: a case report from Turkiye.","journal":"Journal of eating disorders","methods":"","results":"","abstract":"$37","keywords":["ARFID","Adolescent","Avoidant/restrictive food intake disorder","CBT-AR","Case report","Medical complications","Turkey"],"pubmed_id":"41420189","conclusions":"","publication_date":"2025-12-20T00:00:00"},"crossref":{"DOI":"10.1186/s40337-025-01463-z","URL":"https://doi.org/10.1186/s40337-025-01463-z","ISSN":["2050-2974"],"link":[{"URL":"https://link.springer.com/content/pdf/10.1186/s40337-025-01463-z.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/article/10.1186/s40337-025-01463-z","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/content/pdf/10.1186/s40337-025-01463-z.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"1","score":1,"title":["Integrating cognitive-behavioral and medical interventions for ARFID in an adolescent: a case report from Turkiye"],"author":[{"given":"Hakan","family":"Öğütlü","sequence":"first","affiliation":[]},{"given":"İbrahim","family":"Tiryaki","sequence":"additional","affiliation":[]},{"given":"Meryem","family":"Kaşak","sequence":"additional","affiliation":[]},{"given":"Hakan","family":"Türkçapar","sequence":"additional","affiliation":[]},{"given":"Kamyrn T.","family":"Eddy","sequence":"additional","affiliation":[]},{"given":"Jennifer J.","family":"Thomas","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2025,12,19]]},"member":"297","prefix":"10.1186","source":"Crossref","volume":"13","created":{"date-time":"2025-12-19T13:07:30Z","timestamp":1766149650000,"date-parts":[[2025,12,19]]},"indexed":{"date-time":"2025-12-19T14:04:46Z","timestamp":1766153086167,"date-parts":[[2025,12,19]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc-nd/4.0","start":{"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000,"date-parts":[[2025,12,19]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by-nc-nd/4.0","start":{"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000,"date-parts":[[2025,12,19]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://link.springer.com/10.1186/s40337-025-01463-z"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"23 July 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"9 November 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"19 December 2025"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"},"order":1},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"},"order":2,"value":"As this is a single case report, formal ethical approval was not required. 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