Journal of Clinical Psychopharmacology最新文献

{"title":"Improving Result Turnaround Time as a Crucial Factor to Increasing Clozapine Therapeutic Drug Monitoring in Hospitalized Patients.","authors":"Katelyn N Bye, Megan R Leloux, Kristin C Cole, Matej Markota, Nicholas D Allen, Paul J Jannetto, Jonathan G Leung","doi":"10.1097/JCP.0000000000001982","DOIUrl":"https://doi.org/10.1097/JCP.0000000000001982","url":null,"abstract":"<p><strong>Purpose/background: </strong>Clozapine requires careful monitoring to minimize adverse reactions and optimize response. Because of variable pharmacokinetics and interpatient variability, guidelines recommend therapeutic drug monitoring (TDM), although practical guidance is limited. This study aims to characterize patient factors associated with TDM, rates of TDM use over time, turnaround times of TDM results, and influence of institutional initiatives aimed to improve TDM.</p><p><strong>Methods/procedures: </strong>A retrospective chart review was conducted at a large 2000-bed academic medical center from August 1, 2015, to November 26, 2023. Adult patients who were administered clozapine during medical or psychiatric inpatient hospitalizations were included. Data collected included patient demographics, clozapine TDM ordering, and clozapine TDM turnaround time. Yearly TDM rates were analyzed to evaluate the impact of various institutional clozapine-related initiatives on TDM practices.</p><p><strong>Results: </strong>There were 679 encounters involving 334 patients; 62.7 % were men, and 84.4% were White. Younger patients were less likely to have levels drawn (odds ratio 0.98, confidence interval 0.97-0.99), while self-identified Asian patients more likely (odds ratio 7.54, confidence interval 1.60-35.42). TDM rates increased significantly over time for both medical (P = 0.002) and psychiatric (P < 0.001) admission types, with turnaround times improving from 66.07 hours in 2016 to 28.65 hours in 2022. Overall, TDM annual rates increased from 46.2% in 2015 to 69.6% in 2023. The time-period before and after an institutional initiative, which improved TDM turnaround time, was associated with improvements of TDM rates (36.2% vs 67.9%, P < 0.001).</p><p><strong>Conclusions: </strong>This study highlights an increase in clozapine TDM use during the study period, but use remained suboptimal. Improvement of turnaround time was associated with increased TDM rates.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":"45 3","pages":"225-230"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating Real-World Treatment Data Into Clozapine's Product Label.","authors":"Larry Alphs","doi":"10.1097/JCP.0000000000001996","DOIUrl":"10.1097/JCP.0000000000001996","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"177-178"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part II: A Review of Fatal Outcomes in US Pharmacovigilance Data and Proposed Changes.","authors":"Jose de Leon, Ross J Baldessarini, Richard Balon, John Bilbily, Stanley N Caroff, Leslie Citrome, Christoph U Correll, Robert O Cotes, John M Davis, Lynn E DeLisi, Justin Faden, Oliver Freudenreich, David R Goldsmith, Ronald Gurrera, Richard C Josiassen, John M Kane, Deanna L Kelly, Matcheri S Keshavan, Robert S Laitman, Y W Francis Lam, Jonathan G Leung, Raymond C Love, Betsy McCollum, Ian R McGrane, Jonathan M Meyer, Henry A Nasrallah, Frederick C Nucifora, Anthony J Rothschild, Jose M Rubio, Martha Sajatovic, Deepak K Sarpal, Georgios Schoretsanitis, Mujeeb Shad, Charles Shelton, Leo Sher, Balwinder Singh, Sandarsh Surya, Theodore R Zarzar, Emilio J Sanz, Carlos De Las Cuevas","doi":"10.1097/JCP.0000000000001990","DOIUrl":"10.1097/JCP.0000000000001990","url":null,"abstract":"<p><strong>Purpose/background: </strong>This is the second part of a 2-part article that proposes improving the United States (US) clozapine package insert. Part II focuses on fatal outcomes and the 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension and myocarditis, and 1 for all antipsychotics (elderly with dementia).</p><p><strong>Methods: </strong>US reports to the World Health Organization's global pharmacovigilance database were analyzed from clozapine's introduction to January 15, 2023.</p><p><strong>Findings/results: </strong>The US was the top reporter worldwide for clozapine with 56,003 reports and 9587 associated fatal outcomes. The 4 clozapine boxed warnings were associated with 534 fatal outcomes (218 with severe neutropenia, 131 with seizures, 125 with orthostasis, 36 with myocarditis, 24 with cardiomyopathy, and 0 with mitral valve prolapse). With no boxed warnings, pneumonia was associated with 674 fatal outcomes and increased white blood cell count (a sign of infection) with 596 fatal outcomes. After considering overlaps, pneumonia and increases in white blood cell count explained 900 fatalities, or 9.4% of 9587 fatal outcomes. The Food and Drug Administration continues to focus on severe neutropenia which was associated with only 218 or 2.3% of fatal outcomes, whereas 97.7% of fatal outcomes reported in US clozapine-treated patients had another cause.</p><p><strong>Implications/conclusions: </strong>To help prevent future deaths in clozapine-treated patients, the clozapine package insert should focus on fatal outcomes during infections. Part II offers detailed solutions regarding current boxed warnings and lack of a warning for pneumonia and other infections. The Supplementary Material includes letters of support from 124 non-US clozapine experts from 44 countries/regions who support Parts I and II.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"197-218"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navacaprant, a Novel and Highly Selective Kappa Opioid Receptor Antagonist, in Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial.","authors":"Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora","doi":"10.1097/JCP.0000000000001967","DOIUrl":"10.1097/JCP.0000000000001967","url":null,"abstract":"<p><strong>Purpose/background: </strong>This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).</p><p><strong>Methods/procedures: </strong>Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.</p><p><strong>Findings/results: </strong>At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs placebo (least squares mean difference -1.7 [standard error, 1.08], P = 0.121; mixed-models repeated-measures) in the efficacy population. In a prespecified sensitivity analysis using last-observation-carried-forward, navacaprant statistically significantly improved HAMD-17 CFB (-2.9 [0.88], P = 0.002; -2.2 [0.98], P = 0.024) and SHAPS CFB (-2.8 [0.96], P = 0.004; -3.4 [1.10], P = 0.002) vs placebo at weeks 4 and 8. In the prespecified subgroup with moderate-to-severe MDD (baseline HAMD-17 score ≥22; n = 100), navacaprant statistically significantly improved HAMD-17 CFB at both timepoints (-3.0 [1.20], P = 0.015; -2.8 [1.33], P = 0.037) and SHAPS CFB at week 8 (-4.8 [1.35], P = 0.001) vs placebo. Most frequently reported adverse events (AEs) included headache (4.9% both) and nausea (4.9% navacaprant, 1.0% placebo); no serious AEs were reported with navacaprant.</p><p><strong>Implications/conclusions: </strong>Although the primary endpoint was not met in the efficacy population, which included participants with mild depression, statistically significant improvements with navacaprant on depressive symptoms including anhedonia in the moderate-to-severe MDD subgroup, along with a favorable safety profile, support further study of navacaprant for the treatment of MDD.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"267-276"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orofacial Dyskinesia in a Patient With Sotos Syndrome Treated With Methylphenidate.","authors":"Züleyha Ulusoy, Esra Hoşoğlu, Bahadır Turan","doi":"10.1097/JCP.0000000000001988","DOIUrl":"10.1097/JCP.0000000000001988","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"300-301"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Question: Which Antidepressants Would Be Safest to Use in an Elderly Patient, Currently Taking Bupropion, Experiencing Decreasing Renal Function?","authors":"Carl Salzman","doi":"10.1097/JCP.0000000000001991","DOIUrl":"10.1097/JCP.0000000000001991","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"302-303"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Therapeutic Drug Monitoring on Clozapine Dosing and Clinical Outcome in a Tertiary Care Center in India: A Retrospective Study.","authors":"Lakshmi Jogi, Parvathy Praveen, Aromal Shibu, Karthik Narasimhappa, Suhas Satish, Shivarama Varambally, Ganesan Venkatasubramanian, Pratima Murthy, Vijay Kumar","doi":"10.1097/JCP.0000000000001980","DOIUrl":"https://doi.org/10.1097/JCP.0000000000001980","url":null,"abstract":"<p><strong>Background: </strong>There are significant interindividual and interethnic variations in serum clozapine levels achieved for a particular dose of clozapine. Therapeutic drug monitoring (TDM) helps optimize the clozapine dosing. We studied the impact of TDM on clozapine dosing and clinical outcomes in subjects with treatment-resistant schizophrenia.</p><p><strong>Methods: </strong>We compared clozapine dose and clinical outcomes before and after the TDM service implementation in our center, a tertiary care psychiatric facility in India. A retrospective file review of inpatients diagnosed with treatment-resistant schizophrenia and started on clozapine between 2016-2017 (pre-TDM arm; n = 45) and 2021-23 (post-TDM arm; n = 45) was conducted. Clozapine dose in milligrams per day (mg/d), Clinical Global Impression-Improvement scores, and adverse event profile were compared between these groups after 3 months of therapeutic clozapine dose.</p><p><strong>Results: </strong>The median clozapine dose reduced by 100 mg/day after introducing TDM (mean ± SD [median] mg, pre-TDM arm: 276.66 ± 118 [250] mg vs post-TDM arm: 167.22 ± 68 [150] mg, P ≤ 0.0001). However, there was no significant difference in Clinical Global Impression-Improvement score between the 2 groups (pre-TDM arm = median 2; post-TDM arm = median 2, P = 0.33). The incidence of hypersalivation (P = 0.026, odds ratio (95% confidence interval) = 3.06 [1.2-7.6]) and weight gain (P = 0.04, odds ratio [95% CI] = 4.5 [1.1-17.5]) were higher in the pre-TDM group. The median serum clozapine concentration/dose (C/D) ratio was 3 ng/mL/mg in our post-TDM sample of 35, where serum clozapine levels were done.</p><p><strong>Conclusions: </strong>After introducing TDM, there was a significant reduction in clozapine dosage while the magnitude of clinical improvement was comparable.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":"45 3","pages":"251-257"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Pyramidal Sign as an Unexpected Presentation in Antipsychotic-Induced Acute Dystonia: Case Reports and Literature Review.","authors":"Yi-Hui Liu, Ming Chen, Ye-Kai Huang, Wei-Lin Wang, Jia-Rong Liang, Fu-Jun Jia, Cai-Lan Hou","doi":"10.1097/JCP.0000000000001985","DOIUrl":"10.1097/JCP.0000000000001985","url":null,"abstract":"<p><strong>Background: </strong>Acute drug-induced dystonia (DID) is an extrapyramidal side effect triggered by certain medications, primarily antipsychotics. It presents as acute involuntary muscle contractions, causing twisting, repetitive movements, or abnormal postures. Pyramidal signs, typically from upper motor neuron damage, are characterized by positive pathological reflexes, increased muscle tone, and hyperactive tendon reflexes.</p><p><strong>Procedures: </strong>This study describes 2 cases of acute DID following antipsychotic treatment, both presenting with positive pyramidal sign. A literature review was conducted to find reports of abnormal pyramidal signs in acute DID cases, focusing on medical tests for differential diagnosis and neurological assessments related to DID.</p><p><strong>Results: </strong>After reviewing the detailed medication history and conducting comprehensive tests, it was concluded that risperidone and haloperidol caused DID. Adjusting the medication and providing symptomatic treatment led to significant improvement.</p><p><strong>Conclusions: </strong>These cases highlight the importance of being alert to the possibility of acute DID when using antipsychotics and pyramidal signs appear, providing insights for future research into the mechanisms of these unusual symptoms.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"282-286"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pramipexole Augmentation for Treatment-Resistant Unipolar Depression Not Responding to Aripiprazole Augmentation: An Observational Study.","authors":"Antonio Tundo, Sophia Betro', Rocco de Filippis, Roberto Felici, Chiara Lucangeli, Marica Iommi","doi":"10.1097/JCP.0000000000001986","DOIUrl":"10.1097/JCP.0000000000001986","url":null,"abstract":"<p><strong>Background: </strong>At least 50% of patients with treatment-resistant depression (TRD) fail to respond to antidepressant augmentation with aripiprazole (AA), currently the augmentation strategy with the best evidence of efficacy. The present observational study investigated whether pramipexole augmentation (PA) might be useful for patients who failed AA.</p><p><strong>Methods: </strong>We compared the short- and long-term effectiveness and safety of PA in 81 consecutively recruited unipolar patients with TRD, 58 (71.6%) not previously treated with AA (UAA) and 23 (28.4%) who previously failed AA (FAA).</p><p><strong>Results: </strong>The FAA and UAA groups did not differ significantly in terms of remission, response, improvement, and general functioning at 12 and 24 weeks and in terms of freedom from relapse at 12 and 24 months. The response rates at 24 weeks were 69.6% (n = 16) and 77.6% (n = 45), and the remission rates were 60.9% (n = 14) and 74.1% (n = 43), respectively. The rates of sustained response at 24 months were 72.7% (n = 8) and 84.2% (n = 16), respectively. The 2 groups did not differ significantly on safety outcomes (acceptability, tolerability, suicidality and suicide attempts) in the short and long term.</p><p><strong>Conclusions: </strong>Our study showed that the off-label use of PA may be a promising treatment for patients with unipolar TRD who had previously failed respond to AA. The present findings are preliminary and should be interpreted with caution due to study limitations, including the flexibility of the add-on schedule and the small sample size of patients followed up for 12 and 24 months, and need to be confirmed in larger studies.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"236-242"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Article Selected to Receive the Mitchell B. Balter Award.","authors":"Anthony J Rothschild, Richard I Shader, Richard Balon, Susan L McElroy","doi":"10.1097/JCP.0000000000001992","DOIUrl":"10.1097/JCP.0000000000001992","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"304"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}