Journal of Clinical Psychopharmacology最新文献

{"title":"Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I: A Review of the Pharmacokinetic Literature 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 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.0000000000001987","DOIUrl":"https://doi.org/10.1097/JCP.0000000000001987","url":null,"abstract":"<p><strong>Purpose/background: </strong>Clozapine was approved in the United States (US) using 1989 regulations and knowledge. After 30 years, many sections of the US package insert (PI) are outdated.</p><p><strong>Methods: </strong>We comprehensively reviewed the literature to propose PI updates. We present the information in 2 articles. In Part I, we focus on basic pharmacology based on 407 relevant articles. Part II focuses on clinical aspects and pharmacovigilance.</p><p><strong>Findings/results: </strong>Based on more recent expectations of Food and Drug Administration regulations, we reviewed clozapine basic pharmacology including the following: 1) clearance, 2) pharmacokinetics and pharmacodynamics, and 3) monitoring tools. We identified 9 major problems in the basic pharmacological sections of the PI including the following: 1) in vivo studies indicate that clozapine is dependent on CYP1A2 for its metabolism, 2) the minor role of CYP2D6 in clozapine metabolism requires removing the PI recommendation to lower clozapine doses in CYP2D6 poor metabolizers, 3) in nontoxic concentrations CYP3A4 has a minor role in clozapine metabolism and potent CYP3A4 inhibitors lack clinically relevant effects, 4) several drug-drug interactions need to be updated based on recent literature, 5) systemic inflammation may decrease clozapine metabolism and increase the risk of clozapine intoxication, 6) obesity may decrease clozapine metabolism, 7) patients of Asian and Indigenous American ancestry need lower clozapine doses, 8) personalized titration and c-reactive protein monitoring should be considered until prospective studies are available, and 9) the half-life section needs to be modified to acknowledge that single dosing at night is frequent in the US.</p><p><strong>Implications/conclusions: </strong>An improvement in the US clozapine PI may lead to improvement in PIs worldwide.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811618","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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactation-Related Side Effects of Aripiprazole: A Study From Perinatal Psychiatry Services in India.","authors":"Madhuri H Nanjundaswamy, Aana Shah, Shraddha Lotlikar, Rashmi Arasappa, Sundarnag Ganjekar, Harish Thippeswamy, Prabha S Chandra, Geetha Desai","doi":"10.1097/JCP.0000000000001997","DOIUrl":"https://doi.org/10.1097/JCP.0000000000001997","url":null,"abstract":"<p><strong>Background: </strong>Aripiprazole, a prolactin-sparing antipsychotic, is considered relatively safe during pregnancy and has a better metabolic profile compared to other antipsychotics. However, its impact on lactation has not been adequately studied. This study aimed to assess the relationship between aripiprazole use during pregnancy and the postpartum period with lactation outcomes.</p><p><strong>Methods: </strong>Clinical charts of women attending perinatal psychiatry services between January 2016 and December 2021 were reviewed for details of aripiprazole prescription, clinical information, and lactation outcomes. Lactation failure was defined as the total absence of milk flow or secretion of minimal amounts for at least 7 days.</p><p><strong>Results: </strong>Among the 398 women attending perinatal psychiatry services, 60 were prescribed aripiprazole during pregnancy, with lactation data available for 35 women who continued the drug during the postpartum period. The mean age of women in years was 29 (±4.4) years. The most common diagnosis for aripiprazole prescription was schizophrenia (60%). Approximately 54.2% of the women were primiparous. Of the 35 women with available lactation data, 26 (74%) experienced complete lactation failure, and 4 (11%) had insufficient milk production while on aripiprazole. The mean dose of aripiprazole was 16.4 mg/day, with a mean duration of use of 20 months.</p><p><strong>Conclusions: </strong>In this study, most women who continued aripiprazole through pregnancy and postpartum experienced either lactation failure or insufficient milk production. It is important to discuss lactation issues associated with the use of aripiprazole with women during pregnancy and the postpartum period.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811614","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":"Plasma Clozapine in Treatment Refractory Schizophrenia: What Is the Target Range?","authors":"Robert James Flanagan, Stephen John Obee, Alice Hyun Min Kim, Susanna Every-Palmer, Paula Liren Valbuena Sanchez, Lauren Evans, Jonathan Rogers, Suzanne Reeves","doi":"10.1097/JCP.0000000000002007","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002007","url":null,"abstract":"<p><strong>Background: </strong>In treatment-refractory schizophrenia (TRS), a predose plasma concentration of 0.35 mg L-1 is suggested to ensure an adequate trial of clozapine, but the target range may differ between smokers and nonsmokers.</p><p><strong>Method: </strong>We studied data from a clozapine therapeutic drug monitoring service, 1993-2017, with respect to age, sex, smoking status, clozapine dose, estimated clozapine treatment duration, plasma clozapine and norclozapine concentrations, and reason for the request.</p><p><strong>Results: </strong>There were 35,147 and 88,279 samples from 8882 women and 20,378 men, respectively, for which reasons for the request were specified (26,572 samples, 2 reasons; 6421, 3 or more reasons). More samples were sent for analysis due to suspected adverse drug reactions (ADRs) from women (5.3 vs 4.7%, P < 0.001). The median minimum duration of clozapine treatment before the suspected reaction was 156 days shorter in nonsmokers than smokers of either sex (P < 0.001) and shorter in female than male nonsmokers (189 vs 334 d; P < 0.01). The differences in median plasma clozapine concentrations between suspected ADR (1869/4149 samples from women/men, respectively), and control (10,627/25,848 samples from women/men, respectively) groups were small, averaging 0.03 mg L-1 (P < 0.01), but the median plasma clozapine in the ADR and baseline groups was 0.15 mg L-1 lower in smokers than nonsmokers (P < 0.001).</p><p><strong>Implications: </strong>The target ranges associated with response to clozapine and minimal ADRs in TRS may be 0.35-0.45 and 0.50-0.60 mg L-1 in smokers and in nonsmokers, respectively. ADRs may occur earlier in treatment in nonsmokers, particularly in women, who in general have higher predose plasma clozapine concentrations than men.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811647","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":"https://doi.org/10.1097/JCP.0000000000001996","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","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":"Weekly Changes in the Clozapine Concentration-to-Dose Ratio During Clozapine Titration in Japanese Patients With Schizophrenia.","authors":"Yuki Kikuchi, Mutsumi Sakata, Kazuro Ikawa, Daisuke Kume, Naoki Horikawa, Hiroshi Komatsu, Hiroaki Tomita","doi":"10.1097/JCP.0000000000002003","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002003","url":null,"abstract":"<p><strong>Background: </strong>To prevent inflammatory side effects early in the titration phase of clozapine, international guidelines recommend measuring clozapine blood levels weekly. However, data on such measurements are lacking.</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of all patients with schizophrenia who were treated with clozapine for the first time and whose clozapine blood levels were measured for at least 2 consecutive weeks from clozapine initiation at our institution from 2020 to 2024. Patients were divided into 2 groups based on whether they had a fever during the first 6 weeks of clozapine treatment. The clozapine concentration-to-dose (C/D) ratios were compared weekly within 6 weeks after starting clozapine.</p><p><strong>Results: </strong>A total of 28 patients were included in the study, of whom 6 developed a fever and 22 did not. The median C/D ratios in weeks 1 and 2 were significantly higher in patients with a fever than in those without (week 1: 2.12 vs 1.31, P = 0.0217; week 2: 3.48 vs 1.23, P = 0.01). There was no significant difference in C/D ratios between the groups from week 3 to week 6. During the first 6 weeks of treatment, C/D ratios increased markedly and showed peaks in patients with fever but remained stable in patients without fever.</p><p><strong>Conclusions: </strong>Measuring clozapine blood levels early in the titration phase helps estimate the metabolic capacity of patients. Furthermore, it is essential to pay attention to inflammation, which may increase clozapine C/D ratios.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788359","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":"Clozapine Use Among Individuals With Schizophrenia Occurring on the Background of Intellectual Disability and Rare Genetic Variation: A Retrospective Chart Review.","authors":"Mark A Colijn","doi":"10.1097/JCP.0000000000002000","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002000","url":null,"abstract":"<p><strong>Background: </strong>Treatment resistance in schizophrenia is associated with both intellectual disability and rare genetic variation. Information pertaining to the use of clozapine in this context has primarily come from case reports and small case series. Given the frequent occurrence of comorbid medical issues in various genetic disorders and the heightened sensitivity to antipsychotic medications among intellectually disabled individuals, additional information regarding the effectiveness and tolerability of clozapine in this population is needed, particularly in light of its unique side effect profile.</p><p><strong>Methods: </strong>This retrospective review of 1200 charts, which took place at a subspecialty psychiatry clinic, sought to characterize the use of clozapine in individuals with schizophrenia (or psychotic symptoms, generally speaking) and intellectual disability occurring on the background of rare genetic variation, a difficult to study and underserved patient population.</p><p><strong>Results: </strong>Twelve hundred charts were reviewed and 10 eligible individuals were identified, all of whom had been prescribed clozapine and carried a diagnosis of schizophrenia on the background of intellectual disability and rare genetic variation. Six of these 10 individuals harbored presumed pathogenic variants.</p><p><strong>Implications: </strong>This study affirms what is known about clozapine treatment in 22q11.2 deletion syndrome, adds to the scarce literature on Usher syndrome in this context, and provides the first accounts of clozapine use in 22q11.2 microduplication syndrome and DCX variant-related heterotopia.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784377","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":"Exploring the Addictive Potential of Tranylcypromine: A Case Report.","authors":"Livia Beraldo de Lima, Laura Fernandes Berto, Victor Hugo Spitz, João P De Aquino, Rodolfo Furlan Damiano","doi":"10.1097/JCP.0000000000001998","DOIUrl":"https://doi.org/10.1097/JCP.0000000000001998","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784381","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":"Antidepressant non-refill as a Proxy Measure for Medication Acceptability in Electronic Health Records.","authors":"Jorge A Sanchez-Ruiz, Melissa Solares-Bravo, Gregory D Jenkins, Nicolas A Nuñez, Nicole I Leibman, Ahmed T Ahmed, Suzette J Bielinski, Richard M Weinshilboum, Liewei Wang, Mark A Frye, Joanna M Biernacka, Aysegul Ozerdem","doi":"10.1097/JCP.0000000000002001","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002001","url":null,"abstract":"<p><strong>Background: </strong>Pharmacogenomic studies on antidepressant treatment outcomes could be conducted using previously collected data from electronic health record (EHR)-linked biobanks. However, absence of EHR based outcome measures is an unmet need in designing such studies We aimed to define EHR-derived antidepressant outcome measures and explore their utility in showing associations between treatment outcomes and Cytochrome P450 (CYP) metabolizer phenotypes in a proof-of-concept study.</p><p><strong>Methods: </strong>Using data from the EHR-linked cohort, Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT 10K) Study, we collected prescription data and patient health questionnaire 9 (PHQ-9) scores to compute 3 proxy measures for antidepressant response, efficacy, and acceptability: change in PHQ-9 scores, longest treatment interval with a single antidepressant, and antidepressant non-refill. Subsequently, we tested the association of both prescription-based outcomes with DNA-predicted CYP metabolizer phenotypes in European-ancestry participants.</p><p><strong>Results: </strong>We identified 3920 RIGHT 10K participants with at least 1 antidepressant prescription and European-ancestry. Participants had a mean age of 61 years and 72% were women. Implementation of the PHQ-9 outcome was not feasible because of missingness. Of both prescription-based outcomes, antidepressant non-refill reproduced several known antidepressant-CYP interactions. However, the pilot was limited by small subgroups of participants with non-normal metabolizer phenotypes.</p><p><strong>Conclusions: </strong>Derived from structured data, antidepressant non-refill is a promising outcome measure for EHR-linked biobanks that partially reproduced antidepressant-CYP interactions. However, testing on larger datasets is necessary to understand whether it would be a useful for pharmacogenomic research.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803437","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}