Focus (American Psychiatric Publishing)最新文献

{"title":"Combined Ketamine and Cognitive-Behavioral Therapy: Leveraging Metaplasticity to Enhance Treatment Outcomes.","authors":"Morgan S Hardy, S William Li, Samuel T Wilkinson","doi":"10.1176/appi.focus.20260001","DOIUrl":"10.1176/appi.focus.20260001","url":null,"abstract":"<p><p>Over the past two decades, ketamine has emerged as a rapid-acting antidepressant, especially among patients with treatment-resistant depression. As an <i>N</i>-methyl-d-aspartate glutamate receptor antagonist, ketamine has reshaped the understanding of the underlying neurobiological mechanisms of depression treatment. Ketamine induces a transient state of enhanced neuroplasticity and likely potentiates metaplasticity-the brain's increased capacity to undergo future plastic changes. These effects suggest a posttreatment window during which patients are more cognitively flexible and responsive to other interventions. This theoretical framework has led to increasing interest in pairing ketamine with psychotherapies, such as cognitive-behavioral therapy (CBT), to enhance response and reduce relapse after ketamine treatment. This combined approach differs conceptually from ketamine-assisted psychotherapy, which is modeled after psychedelic-assisted therapy and emphasizes the consciousness-altering experience of ketamine as being integral to the therapeutic process. Multiple early studies suggest that CBT or other cognitive therapies delivered after ketamine treatment may leverage the neurobiological changes and cognitive flexibility ketamine induces to produce an enhanced and more durable antidepressant effect. However, the evidence remains limited, and critical parameters such as optimal timing and structure for combined treatment remain undefined. This review summarizes the theoretical rationale for and emerging empirical evidence supporting the integration of ketamine or esketamine with cognitive therapies. The authors evaluate recent clinical trials and highlight gaps in the literature, and conclude with a proposed framework for interventional psychiatrists seeking to incorporate CBT into ketamine-based treatment programs.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 3","pages":"294-306"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Innovation to Implementation: Translating Advances in Psychopharmacology to Clinical Practice.","authors":"Venkat Bhat, Manish K Jha","doi":"10.1176/appi.focus.20260007","DOIUrl":"10.1176/appi.focus.20260007","url":null,"abstract":"","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"113-114"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychopharmacology and Neurocognitive Disorders: Evidence for Cognitive and Behavioral Symptom Management.","authors":"Cody Olson, Marlene Maria Girón Bravo, Gisela Gonzalez, Mary Elizabeth Camp","doi":"10.1176/appi.focus.20250042","DOIUrl":"10.1176/appi.focus.20250042","url":null,"abstract":"<p><p>Neurocognitive disorders (NCDs) encompass various conditions that affect cognition and functioning in activities of daily living. Although many types of NCDs lack curative therapy, medications may be used to ameliorate cognitive as well as behavioral and psychological symptoms of dementia (BPSD). Medications classified as acetylcholinesterase inhibitors, <i>N</i>-methyl-D-aspartate receptor antagonists, and antiamyloid monoclonal antibodies target cognitive symptoms. For BPSD, antidepressants, antipsychotics, mood stabilizers, anxiolytics, and stimulants have been studied. Selection of pharmacotherapies requires careful risk-benefit analysis for individual patients. This review discusses available evidence to guide these discussions and clinical decisions.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"179-187"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Psilocybin in Psychiatric Disorders: Mechanisms, Efficacy, and Clinical Implications.","authors":"Shakila Meshkat, Manish K Jha, Venkat Bhat","doi":"10.1176/appi.focus.20250043","DOIUrl":"10.1176/appi.focus.20250043","url":null,"abstract":"<p><p>Psilocybin, a serotonergic psychedelic, has gained attention as a potential treatment for various psychiatric conditions. In this review, the authors summarize current clinical evidence related to psilocybin's efficacy, safety, and mechanisms of action across psychiatric disorders. Findings from early-phase and small-scale clinical trials suggest rapid but variable reductions in depressive symptoms, with some studies reporting sustained effects. Psilocybin has also shown preliminary benefits in alleviating anxiety related to life-threatening illness and in reducing substance use, including alcohol and tobacco dependence. Emerging but limited evidence supports possible therapeutic effects in the treatment of obsessive-compulsive disorder, body dysmorphic disorder, anorexia nervosa, and posttraumatic stress disorder. Reported adverse events, such as headache, nausea, and short-lived anxiety, are typically transient and mild; however, notable adverse reactions have occurred in larger randomized trials. Mechanistically, psilocybin may act by modulating limbic-prefrontal circuits, promoting synaptic plasticity, and enhancing emotional and cognitive flexibility, in particular when administered alongside structured psychotherapeutic support. Although the existing data are encouraging, the evidence base remains limited by small sample sizes, highly selective populations, and short follow-up durations. Larger, rigorously designed trials are required to confirm efficacy, establish long-term safety, and refine therapeutic protocols. Overall, psilocybin represents a promising but still experimental intervention that warrants further systematic investigation under controlled conditions.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"140-148"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethical and Legal Aspects of Pharmacological Treatment in Psychiatry.","authors":"Jacob M Appel","doi":"10.1176/appi.focus.20250047","DOIUrl":"10.1176/appi.focus.20250047","url":null,"abstract":"","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"191-194"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VMAT2 Inhibitors for Tardive Dyskinesia: What Psychiatrists Should Know.","authors":"Arthur N Westover, Jennifer Perez, Zena Patel, Manish K Jha","doi":"10.1176/appi.focus.20250044","DOIUrl":"10.1176/appi.focus.20250044","url":null,"abstract":"<p><p>Tardive dyskinesia (TD) is characterized by involuntary movements that develop in association with chronic use of antipsychotic medications. While second-generation antipsychotics are associated with lower risk of TD compared with first-generation antipsychotics, their widespread use across a range of chronic mental health conditions (such as psychotic disorders, autism, and mood disorders) has resulted in substantial public health burden of TD. The therapeutic landscape of managing TD has been transformed by the U.S. Food and Drug Administration (FDA) approval of two selective vesicular monoamine transporter 2 (VMAT2) inhibitors in 2017. This report reviews efficacy and safety considerations for the two FDA-approved VMAT2 inhibitors, deutetrabenazine and valbenazine, which are recommended as first-line treatment for troublesome TD in current practice guidelines. Overall, these VMAT2 inhibitors offer significant benefit to patients experiencing TD through improved health and quality of life.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"159-167"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prazosin Monotherapy for Adolescent Posttraumatic Stress Disorder: A Case Report and Narrative Review.","authors":"Baris Olten, Boadie W Dunlop, William V McCall","doi":"10.1176/appi.focus.20250029","DOIUrl":"10.1176/appi.focus.20250029","url":null,"abstract":"<p><p>Pediatric posttraumatic stress disorder (PTSD) is a debilitating condition that is associated with significant functional impairment, diagnostic complexity, and limited evidence-based treatment options. Among its core features, trauma-related sleep disturbances-particularly nightmares-are highly prevalent, profoundly impairing, and contribute to the chronicity and severity of the disorder. Prazosin, a selective alpha₁-adrenergic antagonist, has demonstrated efficacy in adults for reducing nightmares and improving sleep, but pediatric data remain limited. This case report describes an adolescent male patient with chronic PTSD who achieved full symptomatic remission and functional recovery with prazosin monotherapy. The patient had previously failed to respond to multiple psychotropic classes, including antidepressants, mood stabilizers, and antipsychotics. After initiating prazosin and titrating to 3 mg nightly, he experienced rapid and sustained resolution of nightmares, improvement in sleep quality, and overall reduction of PTSD symptomatology. His UCLA Child/Adolescent PTSD Reaction Index scores declined from 61 to 11 over 20 weeks. This case is contextualized within a narrative review of the pediatric prazosin literature, and highlights pharmacologic rationale, safety considerations, and clinical utility. The findings underscore the central role of sleep disturbances as a pivotal treatment target in pediatric PTSD and support further research into prazosin's therapeutic potential in this population.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"199-206"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"I've Done My Research\": Psychedelics, PTSD, and the Therapeutic Alliance.","authors":"Dorothy E Stubbe","doi":"10.1176/appi.focus.20260003","DOIUrl":"10.1176/appi.focus.20260003","url":null,"abstract":"","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"195-198"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Esketamine on Depressive Symptoms in Adolescents With Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study.","authors":"Colette Kosik-Gonzalez, Dong-Jing Fu, Li Nancy Chen, Rosanne Lane, Michael H Bloch, Melissa DelBello, Carmen Moreno, Wayne C Drevets, Carla M Canuso","doi":"10.1176/appi.focus.26024113","DOIUrl":"10.1176/appi.focus.26024113","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate the efficacy, safety, and tolerability of esketamine nasal spray vs psychoactive placebo (oral midazolam) in rapidly reducing depressive symptoms in adolescents with major depressive disorder at imminent risk for suicide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;This double-blind, double-dummy, phase 2b study randomized (1:1:1:2) 147 adolescents (12 to &lt;18 years old) to esketamine (28, 56, or 84 mg) or midazolam twice weekly for 4 weeks. Participants concomitantly received comprehensive standard of care, including initial hospitalization, oral antidepressant, and evidenced-based psychotherapy. The primary efficacy end point-change in Children's Depression Rating Scale-Revised (CDRS-R) total score from baseline to 24 hours post first dose-was analyzed using analysis of covariance, according to a pooled sequential multiple testing procedure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All participants were moderately to severely depressed at enrollment; approximately 95% were moderately to extremely suicidal. Pooled esketamine doses (56 and 84 mg) showed superiority over midazolam in reducing CDRS-R total score at 24 hours post first dose (between-group difference of least squares means [95% CI]:-5.8 [-11.19,-0.35], &lt;i&gt;p&lt;/i&gt; =.037). The between-group differences for individual esketamine 84 mg and 56 mg doses vs midazolam were -5.7 ([-12.91, 1.55], &lt;i&gt;p&lt;/i&gt; =.123) and 5.9 ([12.25, 0.53], &lt;i&gt;p&lt;/i&gt; =.072), respectively. Severity of suicidality, per Clinical Global Impression of Severity of Suicidality-revised (CGI-SS-R), improved in all 4 groups (between-group difference of least squares means [95% CI]:-0.2 [-0.90, 0.41], -0.3 [-0.93, 0.31], 0.0 [-0.69, 0.72] for esketamine 28, 56, and 84 mg, respectively, at 24 hours post first dose). Common adverse events (incidence ≥20%) reported for esketamine were dizziness, nausea, dissociation, headache, dysgeusia, somnolence, vomiting, hypoesthsesia, and intentional self-injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The primary efficacy end point of the study was met for the pooled esketamine doses (56 and 84 mg). Esketamine in conjunction with comprehensive standard of care rapidly improved depressive symptoms among adolescents at imminent risk for suicide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;This double-blind randomized controlled clinical trial compared the effects of esketamine nasal spray (28, 56, or 84 mg) to a psychoactive placebo (midazolam) in 147 adolescents with major depressive disorder who were at imminent risk for suicide. All participants also received standard-of-care treatment, including initial hospitalization, oral antidepressant treatment, and evidenced-based psychotherapy. Combined 56- and 84-mg doses of esketamine were superior to midazolam in reducing depressive symptoms at 24 hours following the first dose; all 4 treatment groups showed continued improvement in depressive symptoms and severity of suicidality after 4 weeks of treatment. The most common side ","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"223-235"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Clinical Applications of Ketamine and Esketamine Across Psychiatric Disorders.","authors":"Rachel Fremont, Marcella Corwin, Greta Kandel, Esha Talati, Jakub Denkiewicz, Rae L Sustana, Keren Bachi, Adriana Feder","doi":"10.1176/appi.focus.20250046","DOIUrl":"10.1176/appi.focus.20250046","url":null,"abstract":"<p><p>Over the past 25 years, the field of psychiatry has seen a rapid expansion of ketamine treatment services offered for the off-label management of depression, anxiety, and other psychiatric disorders as well as the U.S. Food and Drug Administration's approval of intranasal esketamine, the S-enantiomer of ketamine, for treatment-resistant depression and suicidal depression. In this review, the authors describe recent advances in the use of ketamine and esketamine for the treatment of depression and other psychiatric disorders, new research on novel treatment targets, and emerging evidence about ketamine's potential as a prophylactic intervention. Key outstanding issues and limitations of current ketamine treatment also are discussed.</p>","PeriodicalId":73036,"journal":{"name":"Focus (American Psychiatric Publishing)","volume":"24 2","pages":"115-126"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}