2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.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: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.34: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.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"quetiapine: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on quetiapine (generic). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/generic/quetiapine\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Generics\",\"item\":\"https://www.reachrx.ai/hub/tag/generic\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"quetiapine\",\"item\":\"https://www.reachrx.ai/hub/tag/generic/quetiapine\"}]}}"}}]],["$","$L2f",null,{"title":"quetiapine: Research & Clinical Takeaways","description":"Explore research on quetiapine (generic) — efficacy, safety, and comparative data.","papers":[{"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. H.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, German Center for Mental Health, partner site Berlin, Berlin, Germany"},{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}]},{"given":"Christine E.","family":"Dri","sequence":"additional","affiliation":[{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Heidi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Maj","family":"Vinberg","sequence":"additional","affiliation":[{"name":"The Early Multimodular Prevention and Intervention Research Institution, Psychiatric Centre North Zealand, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Taeho Greg","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut"},{"name":"Department of Public Health Sciences, School of Medicine, University of Connecticut, Farmington"}]}],"issued":{"date-parts":[[2026,5,6]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":null,"created":{"date-time":"2026-05-06T15:31:22Z","timestamp":1778081482000,"date-parts":[[2026,5,6]]},"indexed":{"date-time":"2026-05-06T16:16:24Z","timestamp":1778084184274,"date-parts":[[2026,5,6]]},"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2848529"}},"subtitle":["A Systematic Review and Network Meta-Analysis"],"deposited":{"date-time":"2026-05-06T15:31:28Z","timestamp":1778081488000,"date-parts":[[2026,5,6]]},"issn-type":[{"type":"print","value":"2168-622X"}],"published":{"date-parts":[[2026,5,6]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1002/wps.21120","key":"yoi260019r1","year":"2023","issue":"3","author":"McIntyre","volume":"22","first-page":"394","unstructured":null,"article-title":"Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions.","journal-title":"World Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(17)32802-7","key":"yoi260019r2","year":"2018","issue":"10128","author":"Cipriani","volume":"391","first-page":"1357","unstructured":null,"article-title":"Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.","journal-title":"Lancet","doi-asserted-by":"publisher"},{"DOI":"10.1176/ajp.2007.164.2.201","key":"yoi260019r3","year":"2007","issue":"2","author":"Rush","volume":"164","first-page":"201","unstructured":null,"article-title":"STAR*D: what have we learned?","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1136/bmjopen-2022-063095","key":"yoi260019r4","year":"2023","issue":"7","author":"Pigott","volume":"13","first-page":null,"unstructured":null,"article-title":"What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? a reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol.","journal-title":"BMJ Open","doi-asserted-by":"publisher"},{"DOI":"10.1186/s12888-018-1625-y","key":"yoi260019r5","year":"2018","issue":"1","author":"Mago","volume":"18","first-page":"33","unstructured":null,"article-title":"Understanding the emotions of patients with inadequate response to antidepressant treatments: results of an international online survey in patients with major depressive disorder.","journal-title":"BMC Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1001/jamapsychiatry.2021.4313","key":"yoi260019r6","year":"2022","issue":"4","author":"Henssler","volume":"79","first-page":"300","unstructured":null,"article-title":"Combining antidepressants vs antidepressant monotherapy for treatment of patients with acute depression: a systematic review and meta-analysis.","journal-title":"JAMA Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.v68n0207","key":"yoi260019r7","year":"2007","issue":"2","author":"Thase","volume":"68","first-page":"224","unstructured":null,"article-title":"A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.20230922","key":"yoi260019r8","year":"2024","issue":"1","author":"McIntyre","volume":"181","first-page":"26","unstructured":null,"article-title":"Psychotropic drug-related weight gain and its treatment.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1038/s41380-023-02203-y","key":"yoi260019r9","year":"2023","issue":"8","author":"Siafis","volume":"28","first-page":"3267","unstructured":null,"article-title":"Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis.","journal-title":"Mol Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1055/a-1934-9856","key":"yoi260019r10","year":"2023","issue":"1","author":"Nishi","volume":"56","first-page":"5","unstructured":null,"article-title":"Antipsychotic monotherapy for major depressive disorder: a systematic review and meta-analysis.","journal-title":"Pharmacopsychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1097/JCP.0000000000001964","key":"yoi260019r11","year":"2025","issue":"2","author":"Durgam","volume":"45","first-page":"67","unstructured":null,"article-title":"Lumateperone for the treatment of major depressive disorder with mixed features or bipolar depression with mixed features: a randomized placebo-controlled trial.","journal-title":"J Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1092852917000165","key":"yoi260019r12","year":"2017","issue":"2","author":"Stahl","volume":"22","first-page":"203","unstructured":null,"article-title":"Guidelines for the recognition and management of mixed depression.","journal-title":"CNS Spectr","doi-asserted-by":"publisher"},{"DOI":"10.1002/wps.20771","key":"yoi260019r13","year":"2020","issue":"3","author":"Maj","volume":"19","first-page":"269","unstructured":null,"article-title":"The clinical characterization of the adult patient with depression aimed at personalization of management.","journal-title":"World Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.25m15848","key":"yoi260019r14","year":"2025","issue":"4","author":"Durgam","volume":"86","first-page":null,"unstructured":null,"article-title":"Lumateperone as adjunctive therapy in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.20250292","key":"yoi260019r15","year":"2025","issue":"12","author":"Durgam","volume":"182","first-page":"1072","unstructured":null,"article-title":"Adjunctive lumateperone in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.2190/T8EM-C8YH-373N-1UWD","key":"yoi260019r17","year":"1997","issue":"2","author":"Leon","volume":"27","first-page":"93","unstructured":null,"article-title":"Assessing psychiatric impairment in primary care with the Sheehan Disability Scale.","journal-title":"Int J Psychiatry Med","doi-asserted-by":"publisher"},{"DOI":null,"key":"yoi260019r18","year":"2007","issue":"7","author":"Busner","volume":"4","first-page":"28","unstructured":null,"article-title":"The Clinical Global Impressions Scale: applying a research tool in clinical practice.","journal-title":"Psychiatry (Edgmont)","doi-asserted-by":null},{"DOI":"10.1016/S0140-6736(15)00308-6","key":"yoi260019r19","year":"2015","issue":"10011","author":"Lenze","volume":"386","first-page":"2404","unstructured":null,"article-title":"Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.","journal-title":"Lancet","doi-asserted-by":"publisher"},{"DOI":"10.4178/epih.e2019013","key":"yoi260019r20","year":"2019","issue":null,"author":"Shim","volume":"41","first-page":null,"unstructured":null,"article-title":"Network meta-analysis: application and practice using R software.","journal-title":"Epidemiol Health","doi-asserted-by":"publisher"},{"DOI":"10.4178/epih.e2019008","key":"yoi260019r21","year":"2019","issue":null,"author":"Shim","volume":"41","first-page":null,"unstructured":null,"article-title":"Intervention meta-analysis: application and practice using R software.","journal-title":"Epidemiol Health","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.20220504","key":"yoi260019r22","year":"2023","issue":"3","author":"Sachs","volume":"180","first-page":"241","unstructured":null,"article-title":"Adjunctive cariprazine for the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled phase 3 study.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.22m14643","key":"yoi260019r23","year":"2023","issue":"5","author":"Riesenberg","volume":"84","first-page":null,"unstructured":null,"article-title":"Cariprazine for the adjunctive treatment of major depressive disorder in patients with inadequate response to antidepressant therapy: results of a randomized, double-blind, placebo-controlled study.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.64719/pb.4578","key":"yoi260019r24","year":"2018","issue":"4","author":"Earley","volume":"48","first-page":"62","unstructured":null,"article-title":"Cariprazine augmentation to antidepressant therapy in major depressive disorder: results of a randomized, double-blind, placebo-controlled trial.","journal-title":"Psychopharmacol Bull","doi-asserted-by":"publisher"},{"DOI":"10.1097/YIC.0000000000000235","key":"yoi260019r25","year":"2018","issue":"6","author":"Fava","volume":"33","first-page":"312","unstructured":null,"article-title":"Efficacy of adjunctive low-dose cariprazine in major depressive disorder: a randomized, double-blind, placebo-controlled trial.","journal-title":"Int Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.15m10070","key":"yoi260019r26","year":"2016","issue":"3","author":"Durgam","volume":"77","first-page":"371","unstructured":null,"article-title":"Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1111/pcn.13615","key":"yoi260019r27","year":"2024","issue":"2","author":"Kato","volume":"78","first-page":"113","unstructured":null,"article-title":"Adjunctive brexpiprazole 1?mg and 2?mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.","journal-title":"Psychiatry Clin Neurosci","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.17m12058","key":"yoi260019r28","year":"2018","issue":"4","author":"Hobart","volume":"79","first-page":null,"unstructured":null,"article-title":"A randomized, placebo-controlled study of the efficacy and safety of fixed-dose brexpiprazole 2 mg/d as adjunctive treatment of adults with major depressive disorder.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1080/03007995.2018.1430220","key":"yoi260019r29","year":"2018","issue":"4","author":"Hobart","volume":"34","first-page":"633","unstructured":null,"article-title":"Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study.","journal-title":"Curr Med Res Opin","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.14m09689","key":"yoi260019r30","year":"2015","issue":"9","author":"Thase","volume":"76","first-page":"1232","unstructured":null,"article-title":"Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.14m09688","key":"yoi260019r31","year":"2015","issue":"9","author":"Thase","volume":"76","first-page":"1224","unstructured":null,"article-title":"Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1017/neu.2018.23","key":"yoi260019r32","year":"2019","issue":"1","author":"Bauer","volume":"31","first-page":"27","unstructured":null,"article-title":"A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder.","journal-title":"Acta Neuropsychiatr","doi-asserted-by":"publisher"},{"DOI":"10.1111/pcn.12663","key":"yoi260019r33","year":"2018","issue":"8","author":"Kamijima","volume":"72","first-page":"591","unstructured":null,"article-title":"Randomized, double-blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder.","journal-title":"Psychiatry Clin Neurosci","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jad.2013.07.035","key":"yoi260019r34","year":"2013","issue":"3","author":"Kamijima","volume":"151","first-page":"899","unstructured":null,"article-title":"Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study).","journal-title":"J Affect Disord","doi-asserted-by":"publisher"},{"DOI":"10.1159/000332050","key":"yoi260019r35","year":"2012","issue":"2","author":"Fava","volume":"81","first-page":"87","unstructured":null,"article-title":"A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A study).","journal-title":"Psychother Psychosom","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1092852900020216","key":"yoi260019r36","year":"2009","issue":"4","author":"Berman","volume":"14","first-page":"197","unstructured":null,"article-title":"Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants.","journal-title":"CNS Spectr","doi-asserted-by":"publisher"},{"DOI":"10.1097/JCP.0b013e31816774f9","key":"yoi260019r37","year":"2008","issue":"2","author":"Marcus","volume":"28","first-page":"156","unstructured":null,"article-title":"The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study.","journal-title":"J Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1461145710000015","key":"yoi260019r38","year":"2010","issue":"7","author":"El-Khalili","volume":"13","first-page":"917","unstructured":null,"article-title":"Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study.","journal-title":"Int J Neuropsychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.08m04629","key":"yoi260019r39","year":"2009","issue":"4","author":"Bauer","volume":"70","first-page":"540","unstructured":null,"article-title":"Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.v68n0604","key":"yoi260019r40","year":"2007","issue":"6","author":"Berman","volume":"68","first-page":"843","unstructured":null,"article-title":"The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.25m15848","key":"yoi260019r41","year":"2025","issue":"4","author":"Durgam","volume":"86","first-page":null,"unstructured":null,"article-title":"Lumateperone as adjunctive therapy in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.20250292","key":"yoi260019r42","year":"2025","issue":"12","author":"Durgam","volume":"182","first-page":"1072","unstructured":null,"article-title":"Adjunctive lumateperone in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1185/030079908X291958","key":"yoi260019r43","year":"2008","issue":"5","author":"Duru","volume":"24","first-page":"1329","unstructured":null,"article-title":"The clinical relevance of changes in the Montgomery-Asberg Depression Rating Scale using the minimum clinically important difference approach.","journal-title":"Curr Med Res Opin","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1461145714000224","key":"yoi260019r44","year":"2014","issue":"8","author":"Schalkwijk","volume":"17","first-page":"1343","unstructured":null,"article-title":"Declining efficacy in controlled trials of antidepressants: effects of placebo dropout.","journal-title":"Int J Neuropsychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1111/acps.13260","key":"yoi260019r45","year":"2021","issue":"3","author":"Turkoz","volume":"143","first-page":"253","unstructured":null,"article-title":"Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression.","journal-title":"Acta Psychiatr Scand","doi-asserted-by":"publisher"},{"DOI":"10.1016/S2215-0366(24)00314-6","key":"yoi260019r46","year":"2024","issue":"12","author":"Højlund","volume":"11","first-page":"975","unstructured":null,"article-title":"Prevalence, correlates, tolerability-related outcomes, and efficacy-related outcomes of antipsychotic polypharmacy: a systematic review and meta-analysis.","journal-title":"Lancet Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1097/PRA.0000000000000082","key":"yoi260019r47","year":"2015","issue":"4","author":"Preskorn","volume":"21","first-page":"267","unstructured":null,"article-title":"How commonly used inclusion and exclusion criteria in antidepressant registration trials affect study enrollment.","journal-title":"J Psychiatr Pract","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.162.7.1370","key":"yoi260019r48","year":"2005","issue":"7","author":"Zimmerman","volume":"162","first-page":"1370","unstructured":null,"article-title":"Generalizability of antidepressant efficacy trials: differences between depressed psychiatric outpatients who would or would not qualify for an efficacy trial.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1017/neu.2024.32","key":"yoi260019r49","year":"2024","issue":null,"author":"McIntyre","volume":"37","first-page":null,"unstructured":null,"article-title":"A double-blind, placebo-controlled, randomised withdrawal study of adjunctive brexpiprazole maintenance treatment for major depressive disorder.","journal-title":"Acta Neuropsychiatr","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jad.2016.05.013","key":"yoi260019r50","year":"2016","issue":null,"author":"McIntyre","volume":"201","first-page":"116","unstructured":null,"article-title":"Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: results from a post-hoc analysis of two randomised controlled trials.","journal-title":"J Affect Disord","doi-asserted-by":"publisher"},{"DOI":"10.1097/JCP.0000000000001825","key":"yoi260019r51","year":"2024","issue":"2","author":"McIntyre","volume":"44","first-page":"133","unstructured":null,"article-title":"Effects of adjunctive brexpiprazole on individual depressive symptoms and functioning in patients with major depressive disorder and anxious distress: post hoc analysis of three placebo-controlled studies.","journal-title":"J Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.3390/ph18070995","key":"yoi260019r52","year":"2025","issue":"7","author":"Barabassy","volume":"18","first-page":"995","unstructured":null,"article-title":"Transdiagnostic efficacy of cariprazine: a systematic review and meta-analysis of efficacy across ten symptom domains.","journal-title":"Pharmaceuticals (Basel)","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.24m15506","key":"yoi260019r53","year":"2025","issue":"2","author":"Fava","volume":"86","first-page":null,"unstructured":null,"article-title":"Efficacy of adjunctive cariprazine on anxiety symptoms in patients with major depressive disorder: Post hoc analysis of a randomized placebo-controlled trial.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.9758/cpn.23.1106","key":"yoi260019r54","year":"2024","issue":"2","author":"Lee","volume":"22","first-page":"370","unstructured":null,"article-title":"The potential role of aripiprazole augmentation for major depressive disorder with anxious distress in naturalistic treatment setting.","journal-title":"Clin Psychopharmacol Neurosci","doi-asserted-by":"publisher"},{"DOI":"10.1097/JCP.0000000000001420","key":"yoi260019r55","year":"2021","issue":"4","author":"Crapanzano","volume":"41","first-page":"436","unstructured":null,"article-title":"Quetiapine in the anxiety dimension of mood disorders: a systematic review of the literature to support clinical practice.","journal-title":"J Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jad.2025.05.026","key":"yoi260019r56","year":"2025","issue":"119366","author":"McIntyre","volume":"385","first-page":null,"unstructured":null,"article-title":"The effect of adjunctive cariprazine on symptoms of anhedonia in patients with major depressive disorder.","journal-title":"J Affect Disord","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jpsychires.2023.04.012","key":"yoi260019r57","year":"2023","issue":null,"author":"McIntyre","volume":"162","first-page":"71","unstructured":null,"article-title":"Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: post hoc analysis of Inventory of Depressive Symptomatology Self-Report data.","journal-title":"J Psychiatr Res","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jad.2017.10.032","key":"yoi260019r58","year":"2018","issue":null,"author":"Scheggi","volume":"227","first-page":"192","unstructured":null,"article-title":"Aripiprazole relieves motivational anhedonia in rats.","journal-title":"J Affect Disord","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.2018.18091079","key":"yoi260019r59","year":"2019","issue":"5","author":"Zisook","volume":"176","first-page":"348","unstructured":null,"article-title":"General predictors and moderators of depression remission: a VAST-D report.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1002/da.22063","key":"yoi260019r60","year":"2013","issue":"6","author":"McIntyre","volume":"30","first-page":"515","unstructured":null,"article-title":"Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions.","journal-title":"Depress Anxiety","doi-asserted-by":"publisher"},{"DOI":"10.1111/bdi.70049","key":"yoi260019r61","year":"2025","issue":"5","author":"Xiao","volume":"27","first-page":"347","unstructured":null,"article-title":"The efficacy of pharmacological interventions in the treatment of major depressive disorder and bipolar depression with mixed features: a systematic review.","journal-title":"Bipolar Disord","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1092852925100278","key":"yoi260019r62","year":"2025","issue":"1","author":"Teopiz","volume":"30","first-page":null,"unstructured":null,"article-title":"Should glutamatergic modulators be considered preferential treatments for adults with major depressive disorder and a reported history of trauma? conceptual and clinical implications.","journal-title":"CNS Spectr","doi-asserted-by":"publisher"},{"DOI":"10.1080/13543784.2025.2522885","key":"yoi260019r63","year":"2025","issue":"6","author":"McIntyre","volume":"34","first-page":"519","unstructured":null,"article-title":"Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as mechanistically informed treatments for manic episodes, mixed features and cognitive deficits in bipolar disorder?","journal-title":"Expert Opin Investig Drugs","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.su17009ah1c","key":"yoi260019r64","year":"2017","issue":"8","author":"Jain","volume":"78","first-page":"1091","unstructured":null,"article-title":"Diagnosing and treating patients with mixed features.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.2015.15060770","key":"yoi260019r65","year":"2016","issue":"4","author":"Suppes","volume":"173","first-page":"400","unstructured":null,"article-title":"Lurasidone for the treatment of major depressive disorder with mixed features: a randomized, double-blind, placebo-controlled study.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1007/s12325-024-03009-2","key":"yoi260019r66","year":"2025","issue":"1","author":"McIntyre","volume":"42","first-page":"246","unstructured":null,"article-title":"Effect of cariprazine on anhedonia in patients with bipolar I depression: post hoc analysis of three randomized placebo-controlled clinical trials.","journal-title":"Adv Ther","doi-asserted-by":"publisher"},{"DOI":"10.1097/YIC.0000000000000500","key":"yoi260019r67","year":"2024","issue":"2","author":"Jain","volume":"39","first-page":"82","unstructured":null,"article-title":"Efficacy of cariprazine in patients with bipolar depression and higher or lower levels of baseline anxiety: a pooled post hoc analysis.","journal-title":"Int Clin Psychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.4088/JCP.v69n1211","key":"yoi260019r68","year":"2008","issue":"12","author":"Trivedi","volume":"69","first-page":"1928","unstructured":null,"article-title":"Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features.","journal-title":"J Clin Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1002/da.21970","key":"yoi260019r69","year":"2012","issue":"7","author":"Thase","volume":"29","first-page":"574","unstructured":null,"article-title":"Extended release quetiapine fumarate in major depressive disorder: analysis in patients with anxious depression.","journal-title":"Depress Anxiety","doi-asserted-by":"publisher"},{"DOI":"10.1176/appi.ajp.2020.20081251","key":"yoi260019r70","year":"2021","issue":"5","author":"McIntyre","volume":"178","first-page":"383","unstructured":null,"article-title":"Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation.","journal-title":"Am J Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1007/s40263-023-01032-5","key":"yoi260019r71","year":"2023","issue":"10","author":"Akbar","volume":"37","first-page":"867","unstructured":null,"article-title":"Dextromethorphan-bupropion for the treatment of depression: a systematic review of efficacy and safety in clinical trials.","journal-title":"CNS Drugs","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2204462","key":"yoi260019r72","year":"2023","issue":"21","author":"Lenze","volume":"388","first-page":"2013","unstructured":null,"article-title":"Antidepressant augmentation versus switch in treatment-resistant geriatric depression. reply.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2017.8036","key":"yoi260019r73","year":"2017","issue":"2","author":"Mohamed","volume":"318","first-page":"132","unstructured":null,"article-title":"Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1038/s41380-024-02468-x","key":"yoi260019r74","year":"2024","issue":"8","author":"Papakostas","volume":"29","first-page":"2287","unstructured":null,"article-title":"Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.","journal-title":"Mol Psychiatry","doi-asserted-by":"publisher"},{"DOI":"10.1371/journal.pone.0299020","key":"yoi260019r75","year":"2024","issue":"4","author":"Ji","volume":"19","first-page":null,"unstructured":null,"article-title":"Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: a systematic review and meta-analysis of randomized controlled trials.","journal-title":"PLoS One","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.euroneuro.2024.12.013","key":"yoi260019r76","year":"2025","issue":null,"author":"Vieta","volume":"93","first-page":"29","unstructured":null,"article-title":"Improvements in functioning and workplace productivity with esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression: findings from a 32-week randomised, open-label, rater-blinded phase IIIb study.","journal-title":"Eur Neuropsychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1017/S1092852924002451","key":"yoi260019r77","year":"2025","issue":"1","author":"McIntyre","volume":"30","first-page":null,"unstructured":null,"article-title":"Esketamine nasal spray versus quetiapine XR in adults with treatment-resistant depression: a secondary analysis of the ESCAPE-TRD randomized clinical trial.","journal-title":"CNS Spectr","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.euroneuro.2024.05.009","key":"yoi260019r78","year":"2024","issue":null,"author":"McIntyre","volume":"85","first-page":"58","unstructured":null,"article-title":"Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression.","journal-title":"Eur Neuropsychopharmacol","doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2304145","key":"yoi260019r79","year":"2023","issue":"14","author":"Reif","volume":"389","first-page":"1298","unstructured":null,"article-title":"Esketamine nasal spray versus quetiapine for treatment-resistant depression.","journal-title":"N Engl J Med","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jad.2024.04.039","key":"yoi260019r80","year":"2024","issue":null,"author":"Calder","volume":"356","first-page":"753","unstructured":null,"article-title":"Number needed to treat (NNT) for ketamine and esketamine in adults with treatment-resistant depression: a systematic review and meta-analysis.","journal-title":"J Affect Disord","doi-asserted-by":"publisher"},{"DOI":"10.1002/da.20740","key":"yoi260019r81","year":"2010","issue":"10","author":"Liebowitz","volume":"27","first-page":"964","unstructured":null,"article-title":"Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo-controlled trial.","journal-title":"Depress Anxiety","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.pnpbp.2021.110480","key":"yoi260019r82","year":"2022","issue":"110480","author":"Fugger","volume":"114","first-page":null,"unstructured":null,"article-title":"Evidence on sociodemographic and clinical correlates of antidepressant combination or augmentation with second-generation antipsychotics in major depressive disorder.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry","doi-asserted-by":"publisher"},{"DOI":null,"key":"yoi260019r16","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Center for Drug Evaluation, US Food & Drug Administration. Major depressive disorder: developing drugs for treatment. April 24, 2020. Accessed July 4, 2025. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/major-depressive-disorder-developing-drugs-treatment","article-title":null,"journal-title":null,"doi-asserted-by":null}],"short-title":[],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["JAMA Psychiatry"],"reference-count":82,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,5,6]]},"references-count":82,"short-container-title":["JAMA Psychiatry"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1001/jamapsychiatry.2026.0658","is_oa":true,"title":"Adjunctive Antipsychotics in Major Depressive Disorder","updated":"2026-05-12T08:54:10+00:00","published_date":"2026-05-06","best_oa_location":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13150735/","pmh_id":"oai:pubmedcentral.nih.gov:13150735","url_for_pdf":null,"url_for_landing_page":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13150735/"}}},"created_at":"2026-05-12T13:18:08.265Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"brand","value":"Abilify","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"brand","value":"Caplyta","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"brand","value":"Rexulti","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"brand","value":"Seroquel XR","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"brand","value":"Vraylar","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"generic","value":"brexpiprazole","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"generic","value":"cariprazine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"generic","value":"lumateperone","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"sample_size","value":"n=10962","value_numeric":10962},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"warning","value":"All included trials appear to be industry-sponsored; this was noted as a potential source of bias but was not fully assessable from the available text.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"warning","value":"Lumateperone's superior efficacy ranking should be interpreted cautiously given its notably smaller sample size (n=483 vs. >1,200 for other agents), which can widen credible intervals and inflate point estimates in network meta-analyses.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied because this is the first head-to-head network meta-analysis of all 5 FDA-approved adjunctive agents, but independent replication and long-term data are still lacking.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0658","tag_type":"warning","value":"The paper is from May 2026 and is very recent; full text was not accessible, so findings are drawn entirely from the abstract and results sections.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis compared the efficacy (≥50% reduction in MADRS score) and acceptability (all-cause discontinuation) of 5 FDA-approved atypical antipsychotics—aripiprazole, brexpiprazole, cariprazine, lumateperone, and quetiapine XR—as adjunctive treatments in adults with MDD across 22 short-term RCTs (N=10,962).","key_result":"Lumateperone showed the highest efficacy (RR 1.72; 95% CrI 1.40–2.15) but the worst acceptability (RR 2.30; 95% CrI 1.45–3.84 for discontinuation vs. placebo). 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":"10.1192/bjp.2026.10636","pmid":"42057566","title":"Real-world effectiveness of mono- and combination therapies of mood stabilisers and antipsychotics in bipolar disorder: nationwide, within-individual study of 315 046 patients","journal_title":"The British Journal of Psychiatry","journal_issn":"0007-1250","published_at":"2026-04-30T00:00:00.000Z","url":"https://doi.org/10.1192/bjp.2026.10636","source_score":32,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-08T13:23:56.711Z","updated_at":"2026-05-08T13:23:56.711Z","tags":[{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"brexpiprazole","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"sulpiride","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"zotepine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Long-Acting Injectable Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Mood Stabiliser","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"sample_size","value":"n=315,046","value_numeric":315046},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"study_design","value":"Population-Based Cohort Study (Within-Individual Design)","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Findings are from a Japanese population where lithium prescribing rates (~47%) are much higher than in Western countries (~16–17%), which may affect transportability.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Impact flag 'practice_changing' applied due to first systematic real-world evaluation of combination regimens in this scale, but the observational design warrants caution before changing practice.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"The study could not distinguish hospitalisation due to mania, depression, or other psychiatric causes, limiting interpretation of episode-specific effectiveness.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"The study population required ≥2 lifetime lithium prescriptions, which may overrepresent lithium-eligible patients and limit generalisability to those never prescribed lithium.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Zotepine is not approved in the US or EU; clinicians in these regions cannot act on zotepine findings directly.","value_numeric":null}],"summaries":{"what_studied":"This nationwide, population-based cohort study used a within-individual design to compare mono- and combination therapy with mood stabilisers (lithium, valproate, lamotrigine, carbamazepine) and 33+ antipsychotics in 315,046 Japanese adults with bipolar disorder, measuring time to psychiatric hospitalisation over a median 7.1-year follow-up (April 2013–May 2023).","key_result":"All four mood stabiliser monotherapies reduced hospitalisation risk vs. non-use: lithium was strongest (aHR 0.67), followed by valproate (0.71), lamotrigine (0.72), and carbamazepine (0.74). Among antipsychotics, sultopride showed the greatest reduction (aHR 0.53), with aripiprazole LAI (0.62) and oral aripiprazole (0.73) also performing well; quetiapine showed only modest benefit (aHR 0.82), which was dose-dependent (≥300 mg/day: 0.75 vs. <300 mg/day: 0.85). Combination therapy further reduced risk: lithium + carbamazepine (aHR 0.73) and lithium + zotepine (0.82) outperformed lithium alone; lithium + sulpiride increased risk (aHR 1.16). Aripiprazole consistently added benefit across all mood stabiliser backbones (lithium, valproate, lamotrigine).","limitations":"- Residual confounding by indication remains (medications often started during clinical deterioration); the within-individual design reduces but does not eliminate this.\n- Prescription records may not reflect actual adherence; no therapeutic drug monitoring data available.\n- Reason for hospitalisation (mania vs. depression vs. other) could not be determined from reimbursement data.","practice_takeaway":"Lithium remains the most effective mood stabiliser for preventing psychiatric hospitalisation, and adding aripiprazole to any first-line mood stabiliser consistently provides further benefit. Clinicians should be cautious with sulpiride as an add-on to lithium (associated with increased risk) and note that low-dose quetiapine (<300 mg/day) offers minimal protection."}},{"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":"$33","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. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}]},{"given":"Dallas","family":"Seitz","sequence":"additional","affiliation":[{"name":"9Centre for Addiction and Mental Health, Toronto, Ontario, Canada"},{"name":"10Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}]},{"given":"Zahra","family":"Goodarzi","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":"11Division of Geriatric Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"12Division of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada"}]}],"issued":{"date-parts":[[2026,5,7]]},"member":"22","prefix":"10.1146","source":"Crossref","volume":"22","created":{"date-time":"2026-02-12T17:01:06Z","timestamp":1770915666000,"date-parts":[[2026,2,12]]},"indexed":{"date-time":"2026-05-08T03:14:18Z","timestamp":1778210058443,"date-parts":[[2026,5,8]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc-nd/4.0","start":{"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000,"date-parts":[[2026,5,7]]},"delay-in-days":0,"content-version":"unspecified"}],"subject":[],"abstract":"$34","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.annualreviews.org/content/journals/10.1146/annurev-clinpsy-061724-085912"}},"subtitle":[],"deposited":{"date-time":"2026-05-08T02:43:45Z","timestamp":1778208225000,"date-parts":[[2026,5,8]]},"issn-type":[{"type":"print","value":"1548-5943"},{"type":"electronic","value":"1548-5951"}],"published":{"date-parts":[[2026,5,7]]},"publisher":"Annual Reviews","reference":[{"DOI":null,"key":"B1","year":"2015","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1111/jgs.13702","key":"B2","year":"2015","issue":null,"author":null,"volume":"63","first-page":"2227","unstructured":null,"article-title":"American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults","journal-title":"J. Am. Geriatr. Soc.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B3","year":"2017","issue":null,"author":null,"volume":"55","first-page":"727","unstructured":null,"article-title":"The effect of escitalopram on mood and cognition in depressive Alzheimer's disease subjects","journal-title":"J. Alzheimer's Dis.","doi-asserted-by":null},{"DOI":null,"key":"B4","year":"2018","issue":null,"author":null,"volume":"79","first-page":"17r11772","unstructured":null,"article-title":"Meta-analysis of the prevalence of major depressive disorder among older adults with dementia","journal-title":"J. Clin. Psychiatry","doi-asserted-by":null},{"DOI":null,"key":"B5","year":"2020","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":"Programme grants for applied research","journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/S0140-6736(11)60830-1","key":"B6","year":"2011","issue":null,"author":null,"volume":"378","first-page":"403","unstructured":null,"article-title":"Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":null,"key":"B7","year":"2021","issue":null,"author":null,"volume":"2","first-page":"CD013306","unstructured":null,"article-title":"Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":null,"key":"B8","year":"2018","issue":null,"author":null,"volume":"64","first-page":"17","unstructured":null,"article-title":"Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: evidence-based clinical practice guideline","journal-title":"Can. Fam. Physician","doi-asserted-by":null},{"DOI":"10.5770/cgj.21.307","key":"B9","year":"2018","issue":null,"author":null,"volume":"21","first-page":"269","unstructured":null,"article-title":"Interprovincial variation of psychotropic prescriptions dispensed to older Canadian adults","journal-title":"Can. Geriatr. J.","doi-asserted-by":"crossref"},{"DOI":"10.1176/ps.48.10.1289","key":"B10","year":"1997","issue":null,"author":null,"volume":"48","first-page":"1289","unstructured":null,"article-title":"The impact of OBRA-87 on psychotropic drug prescribing in skilled nursing facilities","journal-title":"Psychiatr. Serv.","doi-asserted-by":"crossref"},{"DOI":"10.1177/1471301218762856","key":"B11","year":"2019","issue":null,"author":null,"volume":"18","first-page":"2950","unstructured":null,"article-title":"Managing behavioural and psychological symptoms in community dwelling older people with dementia: 2. A systematic review of qualitative studies","journal-title":"Dementia","doi-asserted-by":"crossref"},{"DOI":"10.5694/j.1326-5377.2003.tb05169.x","key":"B12","year":"2003","issue":null,"author":null,"volume":"178","first-page":"231","unstructured":null,"article-title":"Behavioural and psychological symptoms of dementia: a seven-tiered model of service delivery","journal-title":"Med. J. Aust.","doi-asserted-by":"crossref"},{"DOI":"10.1159/000355912","key":"B13","year":"2013","issue":null,"author":null,"volume":"3","first-page":"386","unstructured":null,"article-title":"The effect of psychosocial support intervention on depression in patients with dementia and their family caregivers: an assessor-blinded randomized controlled trial","journal-title":"Dement. Geriatr. Cogn. Dis. Extra","doi-asserted-by":"crossref"},{"DOI":null,"key":"B14","year":"2020","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1002/gps.6129","key":"B15","year":"2024","issue":null,"author":null,"volume":"39","first-page":"e6129","unstructured":null,"article-title":"Non-pharmacological interventions in the management of dementia-related psychosis: a systematic review and meta-analysis","journal-title":"Int. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2013.12.174","key":"B16","year":"2014","issue":null,"author":null,"volume":"22","first-page":"1565","unstructured":null,"article-title":"Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind and placebo controlled study","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":null,"key":"B17","year":"2012","issue":null,"author":null,"volume":"3","first-page":"73","unstructured":null,"article-title":"Behavioral and psychological symptoms of dementia","journal-title":"Front. Neurol.","doi-asserted-by":null},{"DOI":"10.3233/JAD-200507","key":"B18","year":"2020","issue":null,"author":null,"volume":"78","first-page":"711","unstructured":null,"article-title":"Differences in clinical presentation of behavioral and psychological symptoms of dementia in Alzheimer's disease according to sex and education level","journal-title":"J. Alzheimer's Dis.","doi-asserted-by":"crossref"},{"DOI":"10.1097/WAD.0000000000000302","key":"B19","year":"2019","issue":null,"author":null,"volume":"33","first-page":"154","unstructured":null,"article-title":"Identification of sexual disinhibition in dementia by family caregivers","journal-title":"Alzheimer Dis. Assoc. Disord.","doi-asserted-by":"crossref"},{"DOI":"10.1177/0145445514561317","key":"B20","year":"2015","issue":null,"author":null,"volume":"39","first-page":"390","unstructured":null,"article-title":"Cognitive behavior therapy for anxiety in people with dementia: a clinician guideline for a person-centered approach","journal-title":"Behav. Modif.","doi-asserted-by":"crossref"},{"DOI":"10.1177/07334648211047347","key":"B21","year":"2022","issue":null,"author":null,"volume":"41","first-page":"600","unstructured":null,"article-title":"Telehealth use among older adults during COVID-19: associations with sociodemographic and health characteristics, technology device ownership, and technology learning","journal-title":"J. Appl. Gerontol.","doi-asserted-by":"crossref"},{"DOI":"10.1093/geronj/44.3.M77","key":"B22","year":"1989","issue":null,"author":null,"volume":"44","first-page":"M77","unstructured":null,"article-title":"A description of agitation in a nursing home","journal-title":"J. Gerontol.","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.70224","key":"B23","year":"2025","issue":null,"author":null,"volume":"21","first-page":"e70224","unstructured":null,"article-title":"Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1017/S1041610214001963","key":"B24","year":"2015","issue":null,"author":null,"volume":"27","first-page":"7","unstructured":null,"article-title":"Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition","journal-title":"Int. Psychogeriatr.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2020.09.002","key":"B25","year":"2020","issue":null,"author":null,"volume":"28","first-page":"1256","unstructured":null,"article-title":"Criteria for psychosis in major and mild neurocognitive disorders: International Psychogeriatric Association (IPA) consensus clinical and research definition","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1017/S104161022200103X","key":"B26","year":"2024","issue":null,"author":null,"volume":"36","first-page":"251","unstructured":null,"article-title":"Reduction and prevention of agitation in persons with neurocognitive disorders: an International Psychogeriatric Association consensus algorithm","journal-title":"Int. Psychogeriatr.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B27","year":"1997","issue":null,"author":null,"volume":"48","first-page":"S10","unstructured":null,"article-title":"The Neuropsychiatry Inventory: assessing psychopathology in dementia patients","journal-title":"Neurology","doi-asserted-by":null},{"DOI":"10.1212/WNL.44.12.2308","key":"B28","year":"1994","issue":null,"author":null,"volume":"44","first-page":"2308","unstructured":null,"article-title":"The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia","journal-title":"Neurology","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamaneurol.2023.1835","key":"B29","year":"2023","issue":null,"author":null,"volume":"80","first-page":"813","unstructured":null,"article-title":"Cholinesterase inhibitors for treatment of psychotic symptoms in Alzheimer disease and Parkinson disease: a meta-analysis","journal-title":"JAMA Neurol","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.12335","key":"B30","year":"2021","issue":null,"author":null,"volume":"17","first-page":"1687","unstructured":null,"article-title":"Agitation in Alzheimer's disease: novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1097/WAD.0b013e31822c5bb3","key":"B31","year":"2012","issue":null,"author":null,"volume":"26","first-page":"119","unstructured":null,"article-title":"Three-week nutritional supplementation effect on long-term nutritional status of patients with mild Alzheimer disease","journal-title":"Alzheimer Dis. Assoc. Disord.","doi-asserted-by":"crossref"},{"DOI":"10.1007/s41669-023-00440-z","key":"B32","year":"2023","issue":null,"author":null,"volume":"7","first-page":"887","unstructured":null,"article-title":"Cost-effectiveness of non-pharmacological interventions for mild cognitive impairment and dementia: a systematic review of economic evaluations and a review of reviews","journal-title":"Pharmacoecon. Open","doi-asserted-by":"crossref"},{"DOI":"10.1186/s13195-022-00991-z","key":"B33","year":"2022","issue":null,"author":null,"volume":"14","first-page":"48","unstructured":null,"article-title":"Sex differences in neuropsychiatric symptoms in Alzheimer's disease dementia: a meta-analysis","journal-title":"Alzheimer's Res. Ther.","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa041470","key":"B34","year":"2004","issue":null,"author":null,"volume":"351","first-page":"2509","unstructured":null,"article-title":"Rivastigmine for dementia associated with Parkinson's disease","journal-title":"N. Engl. J. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1007/s40266-018-0546-2","key":"B35","year":"2018","issue":null,"author":null,"volume":"35","first-page":"545","unstructured":null,"article-title":"Efficacy and safety of analgesic treatment for depression in people with advanced dementia: randomised, multicentre, double-blind, placebo-controlled trial (DEP.PAIN.DEM)","journal-title":"Drugs Aging","doi-asserted-by":"crossref"},{"DOI":"10.1097/WAD.0b013e3182087dbc","key":"B36","year":"2011","issue":null,"author":null,"volume":"25","first-page":"213","unstructured":null,"article-title":"The efficacy of nonpharmacological treatment for dementia-related apathy","journal-title":"Alzheimer Dis. Assoc. Disord.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B37","year":"1996","issue":null,"author":null,"volume":"8","first-page":"497","unstructured":null,"article-title":"Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment","journal-title":"Int. Psychogeriatr.","doi-asserted-by":null},{"DOI":"10.1080/07317115.2014.988900","key":"B38","year":"2015","issue":null,"author":null,"volume":"38","first-page":"179","unstructured":null,"article-title":"Ethnicity is an inherent criterion for assessment of individualized music for persons with Alzheimer's disease","journal-title":"Clin. Gerontol.","doi-asserted-by":"crossref"},{"DOI":"10.7326/0003-4819-146-11-200706050-00006","key":"B39","year":"2007","issue":null,"author":null,"volume":"146","first-page":"775","unstructured":null,"article-title":"Antipsychotic drug use and mortality in older adults with dementia","journal-title":"Ann. Intern. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1136/bmj.38330.470486.8F","key":"B40","year":"2005","issue":null,"author":null,"volume":"330","first-page":"445","unstructured":null,"article-title":"Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study","journal-title":"BMJ","doi-asserted-by":"crossref"},{"DOI":"10.1093/geront/gnz140","key":"B41","year":"2020","issue":null,"author":null,"volume":"60","first-page":"896","unstructured":null,"article-title":"Nomenclature used by family caregivers to describe and characterize neuropsychiatric symptoms","journal-title":"Gerontologist","doi-asserted-by":"crossref"},{"DOI":"10.1001/jama.2012.36918","key":"B42","year":"2012","issue":null,"author":null,"volume":"308","first-page":"2020","unstructured":null,"article-title":"Nonpharmacologic management of behavioral symptoms in dementia","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":"10.1093/geront/gnp087","key":"B43","year":"2009","issue":null,"author":null,"volume":"49","first-page":"428","unstructured":null,"article-title":"The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential","journal-title":"Gerontologist","doi-asserted-by":"crossref"},{"DOI":null,"key":"B44","year":"2019","issue":null,"author":null,"volume":"11","first-page":"340","unstructured":null,"article-title":"Detection of anxiety symptoms in persons with dementia: a systematic review","journal-title":"Alzheimer's Dement.","doi-asserted-by":null},{"DOI":null,"key":"B45","year":"2021","issue":null,"author":null,"volume":"13","first-page":"e12169","unstructured":null,"article-title":"Prevalent, persistent, and impairing: longitudinal course and impact of apathy in Alzheimer's disease","journal-title":"Alzheimer's Dement. Diagn. Assess. Dis. Monit.","doi-asserted-by":null},{"DOI":null,"key":"B46","year":"2016","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.5770/cgj.28.820","key":"B47","year":"2025","issue":null,"author":null,"volume":"28","first-page":"91","unstructured":null,"article-title":"The Canadian Coalition for Seniors' Mental Health Canadian clinical practice guidelines for assessing and managing behavioural and psychological symptoms of dementia (BPSD)","journal-title":"Can. Geriatr. J.","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.12035","key":"B48","year":"2020","issue":null,"author":null,"volume":"16","first-page":"541","unstructured":null,"article-title":"Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1186/alzrt201","key":"B49","year":"2013","issue":null,"author":null,"volume":"5","first-page":"S5","unstructured":null,"article-title":"Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012","journal-title":"Alzheimer's Res. Ther.","doi-asserted-by":"crossref"},{"DOI":"10.1177/0269881117714047","key":"B50","year":"2017","issue":null,"author":null,"volume":"31","first-page":"1544","unstructured":null,"article-title":"Myocardial infarction risk and antipsychotics use revisited: a meta-analysis of 10 observational studies","journal-title":"J. Psychopharmacol.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.arr.2022.101568","key":"B51","year":"2022","issue":null,"author":null,"volume":"75","first-page":"101568","unstructured":null,"article-title":"Pharmacological treatments for psychotic symptoms in dementia: a systematic review with pairwise and network meta-analysis","journal-title":"Ageing Res. Rev.","doi-asserted-by":"crossref"},{"DOI":"10.1136/bmj.d4065","key":"B52","year":"2011","issue":null,"author":null,"volume":"343","first-page":"d4065","unstructured":null,"article-title":"Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial","journal-title":"BMJ","doi-asserted-by":"crossref"},{"DOI":"10.3109/15622975.2010.538083","key":"B53","year":"2011","issue":null,"author":null,"volume":"12","first-page":"2","unstructured":null,"article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer's disease and other dementias","journal-title":"World J. Biol. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.12105","key":"B54","year":"2020","issue":null,"author":null,"volume":"16","first-page":"1182","unstructured":null,"article-title":"Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jns.2008.03.023","key":"B55","year":"2008","issue":null,"author":null,"volume":"271","first-page":"97","unstructured":null,"article-title":"A functional neuroimaging study of appetite loss in Alzheimer's disease","journal-title":"J. Neurol. Sci.","doi-asserted-by":"crossref"},{"DOI":"10.1097/JCP.0000000000000710","key":"B56","year":"2017","issue":null,"author":null,"volume":"37","first-page":"347","unstructured":null,"article-title":"Aripiprazole once-monthly in the treatment of acute psychotic episodes in schizophrenia: post hoc analysis of Positive and Negative Syndrome Scale Marder factor scores","journal-title":"J. Clin. Psychopharmacol.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B57","year":"2017","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1111/jgs.15541","key":"B58","year":"2018","issue":null,"author":null,"volume":"66","first-page":"2120","unstructured":null,"article-title":"Personalized goal attainment in dementia care: measuring what persons with dementia and their caregivers want","journal-title":"J. Am. Geriatr. Soc.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2022.12.286","key":"B59","year":"2023","issue":null,"author":null,"volume":"31","first-page":"S10","unstructured":null,"article-title":"Social determinants of health in dementia","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1136/bmj.h369","key":"B60","year":"2015","issue":null,"author":null,"volume":"350","first-page":"h369","unstructured":null,"article-title":"Assessment and management of behavioral and psychological symptoms of dementia","journal-title":"BMJ","doi-asserted-by":"crossref"},{"DOI":null,"key":"B61","year":"2011","issue":null,"author":null,"volume":"68","first-page":"190","unstructured":null,"article-title":"Trends in antipsychotic use in dementia 1999–2007","journal-title":"JAMA","doi-asserted-by":null},{"DOI":"10.3233/JAD-150200","key":"B62","year":"2015","issue":null,"author":null,"volume":"48","first-page":"453","unstructured":null,"article-title":"Depression and suicidal ideation during two psychosocial treatments in older adults with major depression and dementia","journal-title":"J. Alzheimer's Dis.","doi-asserted-by":"crossref"},{"DOI":"10.1017/S0144686X0000502X","key":"B63","year":"1992","issue":null,"author":null,"volume":"12","first-page":"269","unstructured":null,"article-title":"Towards a theory of dementia care: personhood and well-being","journal-title":"Ageing Soc","doi-asserted-by":"crossref"},{"DOI":"10.1017/S1041610213002019","key":"B64","year":"2014","issue":null,"author":null,"volume":"26","first-page":"363","unstructured":null,"article-title":"Variability between nursing homes in prevalence of antipsychotic use in patients with dementia","journal-title":"Int. Psychogeriatr.","doi-asserted-by":"crossref"},{"DOI":"10.1002/(SICI)1099-1166(199602)11:2<97::AID-GPS310>3.0.CO;2-W","key":"B65","year":"1996","issue":null,"author":null,"volume":"11","first-page":"97","unstructured":null,"article-title":"Cognitive therapy for depression in the elderly","journal-title":"Int. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.trci.2017.07.001","key":"B66","year":"2017","issue":null,"author":null,"volume":"3","first-page":"440","unstructured":null,"article-title":"Neuropsychiatric signs and symptoms of Alzheimer's disease: new treatment paradigms","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1111/jgs.19489","key":"B67","year":"2025","issue":null,"author":null,"volume":"73","first-page":"2589","unstructured":null,"article-title":"Treatment of inappropriate sexual behavior in persons with dementia: a systematic review","journal-title":"J. Am. Geriatr. Soc.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.ctim.2018.04.013","key":"B68","year":"2018","issue":null,"author":null,"volume":"38","first-page":"74","unstructured":null,"article-title":"Shiatsu as an adjuvant therapy for depression in patients with Alzheimer's disease: a pilot study","journal-title":"Complement. Ther. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamaneurol.2023.3810","key":"B69","year":"2023","issue":null,"author":null,"volume":"80","first-page":"1307","unstructured":null,"article-title":"Brexpiprazole for the treatment of agitation in Alzheimer dementia: a randomized clinical trial","journal-title":"JAMA Neurol","doi-asserted-by":"crossref"},{"DOI":"10.1176/appi.ajp.2016.15020248","key":"B70","year":"2016","issue":null,"author":null,"volume":"173","first-page":"473","unstructured":null,"article-title":"Effects of citalopram on neuropsychiatric symptoms in Alzheimer's dementia: evidence from the CitAD study","journal-title":"Am. J. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2017.05.015","key":"B71","year":"2018","issue":null,"author":null,"volume":"26","first-page":"25","unstructured":null,"article-title":"Targeted interdisciplinary model for evaluation and treatment of neuropsychiatric symptoms: a cluster randomized controlled trial","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.14522","key":"B72","year":"2025","issue":null,"author":null,"volume":"21","first-page":"e14522","unstructured":null,"article-title":"Optimizing mealtime care and outcomes for people with dementia and their caregivers: a systematic review and meta-analysis of intervention studies","journal-title":"Alzheimer's Dement","doi-asserted-by":"crossref"},{"DOI":null,"key":"B73","year":"2014","issue":null,"author":null,"volume":"18","first-page":"1","unstructured":null,"article-title":"A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia","journal-title":"Health Technol. Assess.","doi-asserted-by":null},{"DOI":"10.1176/jnp.15.1.67","key":"B74","year":"2003","issue":null,"author":null,"volume":"15","first-page":"67","unstructured":null,"article-title":"Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer's disease from 1983 to 2000","journal-title":"J. Neuropsychiatry Clin. Neurosci.","doi-asserted-by":"crossref"},{"DOI":"10.1001/archpsyc.60.7.737","key":"B75","year":"2003","issue":null,"author":null,"volume":"60","first-page":"737","unstructured":null,"article-title":"Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS","journal-title":"Arch. Gen. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1001/jama.288.12.1475","key":"B76","year":"2002","issue":null,"author":null,"volume":"288","first-page":"1475","unstructured":null,"article-title":"Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the Cardiovascular Health Study","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2017.08.014","key":"B77","year":"2017","issue":null,"author":null,"volume":"25","first-page":"1326","unstructured":null,"article-title":"Association between antidepressants and fall-related injuries among long-term care residents","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1097/00019442-200002000-00009","key":"B78","year":"2000","issue":null,"author":null,"volume":"8","first-page":"66","unstructured":null,"article-title":"A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer's disease","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2019.07.014","key":"B79","year":"2020","issue":null,"author":null,"volume":"28","first-page":"410","unstructured":null,"article-title":"Recommendations for the nonpharmacological treatment of apathy in brain disorders","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamapsychiatry.2014.3018","key":"B80","year":"2015","issue":null,"author":null,"volume":"72","first-page":"438","unstructured":null,"article-title":"Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm","journal-title":"JAMA Psychiatry","doi-asserted-by":"crossref"},{"DOI":null,"key":"B81","year":"2020","issue":null,"author":null,"volume":"11","first-page":"CD009178","unstructured":null,"article-title":"Pharmacotherapies for sleep disturbances in dementia","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":"10.1093/ageing/afaf014","key":"B82","year":"2025","issue":null,"author":null,"volume":"54","first-page":"afaf014","unstructured":null,"article-title":"Deprescribing in cognitively vulnerable older people: development and validation of STOPPCog criteria","journal-title":"Age Ageing","doi-asserted-by":"crossref"},{"DOI":"10.1016/S0140-6736(00)03399-7","key":"B83","year":"2000","issue":null,"author":null,"volume":"356","first-page":"2031","unstructured":null,"article-title":"Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study","journal-title":"Lancet","doi-asserted-by":"crossref"},{"DOI":null,"key":"B84","year":"2019","issue":null,"author":null,"volume":"3","first-page":"CD003154","unstructured":null,"article-title":"Memantine for dementia","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":"10.1002/gps.3762","key":"B85","year":"2012","issue":null,"author":null,"volume":"27","first-page":"1163","unstructured":null,"article-title":"Specialist mental health consultation for depression in Australian aged care residents with dementia: a cluster randomized trial","journal-title":"Int. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1002/alz.12358","key":"B86","year":"2021","issue":null,"author":null,"volume":"17","first-page":"1892","unstructured":null,"article-title":"Diagnostic criteria for apathy in neurocognitive disorders","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamaneurol.2021.3356","key":"B87","year":"2021","issue":null,"author":null,"volume":"78","first-page":"1324","unstructured":null,"article-title":"Effect of methylphenidate on apathy in patients with Alzheimer disease: the ADMET 2 randomized clinical trial","journal-title":"JAMA Neurol","doi-asserted-by":"crossref"},{"DOI":"10.1136/bmj-2023-076268","key":"B88","year":"2024","issue":null,"author":null,"volume":"385","first-page":"e076268","unstructured":null,"article-title":"Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study","journal-title":"BMJ","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jpainsymman.2020.08.034","key":"B89","year":"2021","issue":null,"author":null,"volume":"61","first-page":"438","unstructured":null,"article-title":"Racial/ethnic differences in staff-assessed pain behaviors among newly admitted nursing home residents","journal-title":"J. Pain Symptom Manag.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B90","year":"2016","issue":null,"author":null,"volume":"8","first-page":"1","unstructured":null,"article-title":"Neuropsychiatric symptoms in dementia and the effects of Ginkgo biloba extract EGb 761® treatment: additional results from a 24-week randomized, placebo-controlled trial","journal-title":"Open Access J. Clin. Trials","doi-asserted-by":null},{"DOI":"10.1002/alz.14282","key":"B91","year":"2024","issue":null,"author":null,"volume":"20","first-page":"8002","unstructured":null,"article-title":"Brexpiprazole treatment for agitation in Alzheimer's dementia: a randomized study","journal-title":"Alzheimer's Dement.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B92","year":"2019","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1186/s40478-023-01576-z","key":"B93","year":"2023","issue":null,"author":null,"volume":"11","first-page":"89","unstructured":null,"article-title":"Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort","journal-title":"Acta Neuropathol. Commun.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B94","year":"2018","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.neubiorev.2023.105507","key":"B95","year":"2024","issue":null,"author":null,"volume":"157","first-page":"105507","unstructured":null,"article-title":"Clinical effectiveness of pharmacological and non-pharmacological treatments for the management of anxiety in community dwelling people living with dementia: a systematic review and meta-analysis","journal-title":"Neurosci. Biobehav. Rev.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B96","year":"2017","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.jagp.2025.06.016","key":"B97","year":"2025","issue":null,"author":null,"volume":"33","first-page":"1331","unstructured":null,"article-title":"The impact of nondepressive neuropsychiatric symptoms on mortality in dementia: a systematic review and meta-analysis","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1097/00019442-200203000-00003","key":"B98","year":"2002","issue":null,"author":null,"volume":"10","first-page":"125","unstructured":null,"article-title":"Provisional diagnostic criteria for depression of Alzheimer disease","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1111/imj.13215","key":"B99","year":"2016","issue":null,"author":null,"volume":"46","first-page":"1189","unstructured":null,"article-title":"Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel","journal-title":"Intern. Med. J.","doi-asserted-by":"crossref"},{"DOI":"10.1111/hex.70289","key":"B100","year":"2025","issue":null,"author":null,"volume":"28","first-page":"e70289","unstructured":null,"article-title":"Reimagining dementia care: a complex intervention systematic review on optimising social prescribing (SP) for people living with dementia (PLWD) in the United Kingdom","journal-title":"Health Expectations","doi-asserted-by":"crossref"},{"DOI":null,"key":"B101","year":"2021","issue":null,"author":null,"volume":"2","first-page":"CD009081","unstructured":null,"article-title":"Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":"10.1001/jama.2014.93","key":"B102","year":"2014","issue":null,"author":null,"volume":"311","first-page":"682","unstructured":null,"article-title":"Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":null,"key":"B103","year":"2014","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1038/s41591-025-03569-y","key":"B104","year":"2025","issue":null,"author":null,"volume":"31","first-page":"1586","unstructured":null,"article-title":"Escitalopram for agitation in Alzheimer's dementia: a randomized controlled phase 3 trial","journal-title":"Nat. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jamda.2016.04.006","key":"B105","year":"2016","issue":null,"author":null,"volume":"17","first-page":"741","unstructured":null,"article-title":"Apathy and its response to antipsychotic review and nonpharmacological interventions in people with dementia living in nursing homes: WHELD, a factorial cluster randomized controlled trial","journal-title":"J. Am. Med. Dir. Assoc.","doi-asserted-by":"crossref"},{"DOI":"10.5694/mja2.50015","key":"B106","year":"2019","issue":null,"author":null,"volume":"210","first-page":"174","unstructured":null,"article-title":"Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary","journal-title":"Med. J. Aust.","doi-asserted-by":"crossref"},{"DOI":"10.1080/08952841.2020.1735925","key":"B107","year":"2021","issue":null,"author":null,"volume":"33","first-page":"635","unstructured":null,"article-title":"Gender differences in presentation and management of behavioral and psychological symptoms associated with dementia among nursing home residents with moderate to severe dementia","journal-title":"J. Women Aging","doi-asserted-by":"crossref"},{"DOI":"10.1176/appi.ajp.2015.173501","key":"B108","year":"2016","issue":null,"author":null,"volume":"173","first-page":"543","unstructured":null,"article-title":"The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia","journal-title":"Am. J. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1186/s12877-017-0636-8","key":"B109","year":"2017","issue":null,"author":null,"volume":"17","first-page":"244","unstructured":null,"article-title":"Antipsychotics and dementia in Canada: a retrospective cross-sectional study of four health sectors","journal-title":"BMC Geriatr","doi-asserted-by":"crossref"},{"DOI":"10.1111/jgs.12061","key":"B110","year":"2013","issue":null,"author":null,"volume":"61","first-page":"55","unstructured":null,"article-title":"Older men with dementia are at greater risk than women of serious events after initiating antipsychotic therapy","journal-title":"J. Am. Geriatr. Soc.","doi-asserted-by":"crossref"},{"DOI":"10.1159/000354366","key":"B111","year":"2013","issue":null,"author":null,"volume":"36","first-page":"340","unstructured":null,"article-title":"The effect of person-centred dementia care to prevent agitation and other neuropsychiatric symptoms and enhance quality of life in nursing home patients: a 10-month randomized controlled trial","journal-title":"Dement. Geriatr. Cogn. Disord.","doi-asserted-by":"crossref"},{"DOI":"10.1097/JGP.0b013e3181c796eb","key":"B112","year":"2010","issue":null,"author":null,"volume":"18","first-page":"136","unstructured":null,"article-title":"Sertraline for the treatment of depression in Alzheimer disease","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.4088/JCP.12m08099","key":"B113","year":"2013","issue":null,"author":null,"volume":"74","first-page":"810","unstructured":null,"article-title":"Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial","journal-title":"J. Clin. Psychiatry","doi-asserted-by":"crossref"},{"DOI":null,"key":"B114","year":"2018","issue":null,"author":null,"volume":"5","first-page":"CD012197","unstructured":null,"article-title":"Pharmacological interventions for apathy in Alzheimer's disease","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":"10.1016/j.jamda.2016.09.019","key":"B115","year":"2017","issue":null,"author":null,"volume":"18","first-page":"87.e15","unstructured":null,"article-title":"Risk of hip fracture in benzodiazepine users with and without Alzheimer disease","journal-title":"J. Am. Med. Dir. Assoc.","doi-asserted-by":"crossref"},{"DOI":"10.1001/jama.2024.25845","key":"B116","year":"2025","issue":null,"author":null,"volume":"333","first-page":"962","unstructured":null,"article-title":"Palliative care program for community-dwelling individuals with dementia and caregivers: the IN-PEACE randomized clinical trial","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":"10.14283/jpad.2018.15","key":"B117","year":"2018","issue":null,"author":null,"volume":"5","first-page":"98","unstructured":null,"article-title":"Identifying better outcome measures to improve treatment of agitation in dementia: a report from the EU/US/CTAD Task Force","journal-title":"J. Prev. Alzheimer's Dis.","doi-asserted-by":"crossref"},{"DOI":"10.1024/1661-8157/a001547","key":"B118","year":"2014","issue":null,"author":null,"volume":"103","first-page":"135","unstructured":null,"article-title":"Recommendations for the diagnosis and treatment of behavioral and psychological symptoms of dementia (BPSD)","journal-title":"Praxis","doi-asserted-by":"crossref"},{"DOI":"10.1017/cjn.2016.426","key":"B119","year":"2017","issue":null,"author":null,"volume":"44","first-page":"267","unstructured":null,"article-title":"Pharmacological therapy for apathy in Alzheimer's disease: a systematic review and meta-analysis","journal-title":"Can. J. Neurol. Sci.","doi-asserted-by":"crossref"},{"DOI":"10.1093/geront/gnx083","key":"B120","year":"2018","issue":null,"author":null,"volume":"58","first-page":"e239","unstructured":null,"article-title":"Reducing antipsychotic medication use in nursing homes: a qualitative study of nursing staff perceptions","journal-title":"Gerontologist","doi-asserted-by":"crossref"},{"DOI":"10.1001/jama.2023.13239","key":"B121","year":"2023","issue":null,"author":null,"volume":"330","first-page":"512","unstructured":null,"article-title":"Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":"10.1111/j.1468-1331.2012.03784.x","key":"B122","year":"2012","issue":null,"author":null,"volume":"19","first-page":"1159","unstructured":null,"article-title":"EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia","journal-title":"Eur. J. Neurol.","doi-asserted-by":"crossref"},{"DOI":"10.1136/jnnp-2016-313660","key":"B123","year":"2016","issue":null,"author":null,"volume":"87","first-page":"1368","unstructured":null,"article-title":"Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis","journal-title":"J. Neurol. Neurosurg. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1192/bjp.bp.113.140087","key":"B124","year":"2015","issue":null,"author":null,"volume":"206","first-page":"509","unstructured":null,"article-title":"Cognitive-behavioural therapy for anxiety in dementia: pilot randomised controlled trial","journal-title":"Br. J. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jagp.2013.01.007","key":"B125","year":"2013","issue":null,"author":null,"volume":"21","first-page":"696","unstructured":null,"article-title":"The Peaceful Mind program: a pilot test of a cognitive-behavioral therapy-based intervention for anxious patients with dementia","journal-title":"Am. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1002/gps.1858","key":"B126","year":"2008","issue":null,"author":null,"volume":"23","first-page":"170","unstructured":null,"article-title":"Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study","journal-title":"Int. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1177/0091270011405665","key":"B127","year":"2012","issue":null,"author":null,"volume":"52","first-page":"947","unstructured":null,"article-title":"New insights: dose-response relationship between psychotropic drugs and falls: a study in nursing home residents with dementia","journal-title":"J. Clin. Pharmacol.","doi-asserted-by":"crossref"},{"DOI":"10.1503/cmaj.160126","key":"B128","year":"2017","issue":null,"author":null,"volume":"189","first-page":"E519","unstructured":null,"article-title":"Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease","journal-title":"CMAJ","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa2034634","key":"B129","year":"2021","issue":null,"author":null,"volume":"385","first-page":"309","unstructured":null,"article-title":"Trial of pimavanserin in dementia-related psychosis","journal-title":"N. Engl. J. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1093/geronb/52B.4.P159","key":"B130","year":"1997","issue":null,"author":null,"volume":"52B","first-page":"159","unstructured":null,"article-title":"Behavioral treatment of depression in dementia patients: a controlled clinical trial","journal-title":"J. Gerontol.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jamda.2014.06.012","key":"B131","year":"2014","issue":null,"author":null,"volume":"15","first-page":"706","unstructured":null,"article-title":"Interventions to reduce inappropriate prescribing of antipsychotic medications in people with dementia resident in care homes: a systematic review","journal-title":"J. Am. Med. Dir. Assoc.","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.eurpsy.2014.02.004","key":"B132","year":"2015","issue":null,"author":null,"volume":"30","first-page":"251","unstructured":null,"article-title":"Apathy in nursing home residents with dementia: results from a cluster-randomized controlled trial","journal-title":"Eur. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1001/jama.289.2.210","key":"B133","year":"2003","issue":null,"author":null,"volume":"289","first-page":"210","unstructured":null,"article-title":"Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis","journal-title":"JAMA","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMoa2212948","key":"B134","year":"2023","issue":null,"author":null,"volume":"388","first-page":"9","unstructured":null,"article-title":"Lecanemab in early Alzheimer's disease","journal-title":"N. Engl. J. Med.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B135","year":"2018","issue":null,"author":null,"volume":"3","first-page":"CD007726","unstructured":null,"article-title":"Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":null,"key":"B136","year":"2023","issue":null,"author":null,"volume":"15","first-page":"e12398","unstructured":null,"article-title":"A data-driven examination of apathy and depressive symptoms in dementia with independent replication","journal-title":"Alzheimer's Dement.","doi-asserted-by":null},{"DOI":"10.1017/S0033291704003897","key":"B137","year":"2005","issue":null,"author":null,"volume":"35","first-page":"307","unstructured":null,"article-title":"Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies","journal-title":"Psychol. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1002/gps.2586","key":"B138","year":"2011","issue":null,"author":null,"volume":"26","first-page":"723","unstructured":null,"article-title":"The effects of a nursing guideline on depression in psychogeriatric nursing home residents with dementia","journal-title":"Int. J. Geriatr. Psychiatry","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.clnu.2015.09.004","key":"B139","year":"2015","issue":null,"author":null,"volume":"34","first-page":"1052","unstructured":null,"article-title":"ESPEN guidelines on nutrition in dementia","journal-title":"Clin. Nutr.","doi-asserted-by":"crossref"},{"DOI":null,"key":"B140","year":"2021","issue":null,"author":null,"volume":"374","first-page":"n1925","unstructured":null,"article-title":"Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series","journal-title":"BMJ","doi-asserted-by":null},{"DOI":"10.1093/ageing/afab218","key":"B141","year":"2022a","issue":null,"author":null,"volume":"51","first-page":"afab218","unstructured":null,"article-title":"Barriers and facilitators to virtual care in a geriatric medicine clinic: a semi-structured interview study of patient, caregiver and healthcare provider perspectives","journal-title":"Age Ageing","doi-asserted-by":"crossref"},{"DOI":"10.1503/cmaj.180551","key":"B142","year":"2018","issue":null,"author":null,"volume":"190","first-page":"E1376","unstructured":null,"article-title":"Comparative risk of harm associated with trazodone or atypical antipsychotic use in older adults with dementia: a retrospective cohort study","journal-title":"CMAJ","doi-asserted-by":"crossref"},{"DOI":"10.7326/M19-0993","key":"B143","year":"2019","issue":null,"author":null,"volume":"171","first-page":"633","unstructured":null,"article-title":"Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis","journal-title":"Ann. Intern. Med.","doi-asserted-by":"crossref"},{"DOI":"10.1186/s12877-020-01607-7","key":"B144","year":"2020","issue":null,"author":null,"volume":"20","first-page":"212","unstructured":null,"article-title":"Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis","journal-title":"BMC Geriatr","doi-asserted-by":"crossref"},{"DOI":null,"key":"B145","year":"2021","issue":null,"author":null,"volume":"372","first-page":"n532","unstructured":null,"article-title":"Comparative efficacy of interventions for reducing symptoms of depression in people with dementia: systematic review and network meta-analysis","journal-title":"BMJ","doi-asserted-by":null},{"DOI":"10.1016/j.jamda.2024.03.007","key":"B146","year":"2024","issue":null,"author":null,"volume":"25","first-page":"837","unstructured":null,"article-title":"Guideline recommendations on behavioral and psychological symptoms of dementia: a systematic review","journal-title":"J. Am. Med. Dir. Assoc.","doi-asserted-by":"crossref"},{"DOI":"10.1136/bmj-2021-069187","key":"B147","year":"2022b","issue":null,"author":null,"volume":"376","first-page":"e069187","unstructured":null,"article-title":"Managing neuropsychiatric symptoms in patients with dementia","journal-title":"BMJ","doi-asserted-by":"crossref"},{"DOI":null,"key":"B148","year":"2015","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":null,"key":"B149","year":"2023","issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":"Non-pharmacological interventions for sleep disturbances in people with dementia","journal-title":"Cochrane Database Syst. Rev.","doi-asserted-by":null},{"DOI":"10.1093/ageing/afac047","key":"B150","year":"2022","issue":null,"author":null,"volume":"51","first-page":"afac047","unstructured":null,"article-title":"Family carer perspectives on the language of behaviour change in dementia: an online mixed methods survey","journal-title":"Age Ageing","doi-asserted-by":"crossref"},{"DOI":"10.1001/jamanetworkopen.2019.0828","key":"B151","year":"2019","issue":null,"author":null,"volume":"2","first-page":"e190828","unstructured":null,"article-title":"Assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia: a network meta-analysis","journal-title":"JAMA Netw. Open","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.jamda.2023.01.014","key":"B152","year":"2023","issue":null,"author":null,"volume":"24","first-page":"555","unstructured":null,"article-title":"State variation in antipsychotic use among assisted living residents with dementia","journal-title":"J. Am. Med. Dir. Assoc.","doi-asserted-by":"crossref"}],"short-title":[],"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,5,7]]}},"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["Annual Review of Clinical Psychology"],"published-print":{"date-parts":[[2026,5,7]]},"reference-count":152,"published-online":null,"references-count":152,"short-container-title":[],"is-referenced-by-count":1},"unpaywall":{"doi":"10.1146/annurev-clinpsy-061724-085912","is_oa":false,"title":"Management of Behavioral and Psychological Symptoms of Dementia: Nonpharmacologic and Pharmacologic Interventions","updated":"2026-02-13T15:49:00+00:00","published_date":"2026-02-12","best_oa_location":null}},"created_at":"2026-05-12T13:18:16.305Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Behavioral and Psychological Symptoms of Dementia","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Dementia with Lewy Bodies","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Mild Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"condition","value":"Vascular Dementia","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"citalopram","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"donepezil","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"galantamine","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"memantine","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"generic","value":"rivastigmine","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"modality","value":"Acetylcholinesterase Inhibitor","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"modality","value":"Nonpharmacological Intervention","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"modality","value":"Selective Serotonin Reuptake Inhibitor","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"warning","value":"Mortality risk data for antipsychotics (OR 1.54) is from a 2005 meta-analysis cited within the guideline; more recent estimates may differ.","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"warning","value":"No sample size tag was applied as this is a guideline synthesis, not a single primary study with a defined N.","value_numeric":null},{"paper_doi":"10.1146/annurev-clinpsy-061724-085912","tag_type":"warning","value":"The full text extracted is the 2016 Australian NHMRC Clinical Practice Guideline, not the 2026 Annual Review of Clinical Psychology article referenced in the DOI metadata — these appear to be two different documents. 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."}}],"initialOffset":6,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"generic","value":"quetiapine"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Generics","href":"/hub/tag/generic"},{"name":"quetiapine"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"generic","hub_tag_value":"quetiapine"}}}]]

Papers