93 results on '"Jonathan G. Leung"'
Search Results
2. The potential influence of estrogen-containing oral contraception on clozapine metabolism in a patient with known pharmacogenomic status
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Alyssa K. Kuhn, Meina L. Determan, Jessica A. Wright, PharmD, Eric Matey, and Jonathan G. Leung
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clozapine ,oral contraceptives ,cyp1a2 ,pharmacogenomics ,schizophrenia ,estrogen ,progestin ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Pharmacy and materia medica ,RS1-441 - Abstract
Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient’s pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.
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- 2024
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3. Evaluation of major adverse events of clozapine based on accordance to an international titration guideline
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Matthew Nuebel, PharmD, Jonathan G. Leung, PharmD, Christopher Hughes, PhD, and Ian McGrane, PharmD
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antipsychotic agents ,clozapine ,dose-response relationship ,drug ,drug-related side effects and adverse reactions ,inflammation ,schizophrenia spectrum and other psychotic disorders ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Pharmacy and materia medica ,RS1-441 - Abstract
Introduction Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated. Methods A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient’s cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring. Results Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal. Discussion Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.
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- 2024
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4. Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder
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Nicolas A. Nuñez, Brandon J. Coombes, Lindsay Melhuish Beaupre, Aysegul Ozerdem, Manuel Gardea Resendez, Francisco Romo-Nava, David J. Bond, Marin Veldic, Balwinder Singh, Katherine M. Moore, Hannah K. Betcher, Simon Kung, Miguel L. Prieto, Manuel Fuentes, Mete Ercis, Alessandro Miola, Jorge A. Sanchez Ruiz, Gregory Jenkins, Anthony Batzler, Jonathan G. Leung, Alfredo Cuellar-Barboza, Susannah J. Tye, Susan L. McElroy, Joanna M. Biernacka, and Mark A. Frye
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.
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- 2024
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5. Ethnopsychopharmacology: Clinical and scientific writing pearls
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Jonathan G. Leung, PharmD, BCPS, BCPP
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ethnopsychopharmacology ,antipsychotics ,antidepressants ,pharmacogenomics ,precision medicine ,clozapine ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Pharmacy and materia medica ,RS1-441 - Abstract
The concept of ethnopsychopharmacology aims to predict or explain the pharmacologic response to psychiatric medications based on the influence of biologic and nonbiologic factors. Interactions involving these factors are complex and influence patient outcomes in health care. Pharmacists and other clinicians working in patient care environments, research, or medical education should engage in lifelong learning to enhance ethnopsychopharmacologic knowledge gaps, which ultimately may improve and individualize care across diverse populations. Through two cases, this paper provides pearls on how biogeographical ancestry and cytochrome P450 status may influence pharmacotherapy selection, dosing, or response. A third scenario highlights a publication, like many other published works, with deficiencies in how data on ancestry, race, and ethnicity are collected or reported. Current recommendations on the use of inclusive language in scientific writing are reviewed, with attention to specific examples.
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- 2023
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6. Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes
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Dylan L. Kosaski, PharmD, Kristin C. Cole, Jessica A. Wright, Razan M. El Melik, PharmD, Simon Kung, MD, Wayne T. Nicholson, MD, PharmD, and Jonathan G. Leung, PharmD
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antidepressants ,depression ,drug interactions ,pharmacogenomics ,pharmacokinetics ,cytochrome p450 ,sex ,gender ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Pharmacy and materia medica ,RS1-441 - Abstract
Introduction: Although there are studies assessing reasons for antidepressant discontinuation, little is known about the impact of sex differences or cytochrome P450 phenotypes. Our objective is to assess discontinuation rates between males and females and whether CYP450 phenotype influences discontinuation. Methods: This is a retrospective review of patients previously enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment database with major depressive disorder. Patients were evaluated for antidepressants trialed between January 1, 2009, and September 30, 2019. Survival analyses with competing risks were used to analyze discontinuation reasons. A Kaplan-Meier estimation method was used to assess the time to discontinuation and discontinuation rates. Analyses were also completed to assess discontinuation between men and women by phenotypic groups. All tests were two-sided, and p-values ≤ .05 were considered statistically significant. Results: There were 620 antidepressant discontinuation events discovered from 1015 antidepressant trials included. Overall, the median time to discontinuation for males was 2.6 years and 1.9 years for females (hazard ratio [HR] 0.97 [95% confidence interval (CI): 0.80, 1.19], p = .77). The risk of discontinuation was not different between males and females in any of the phenotype groups, which was consistent in the multivariable analyses. Concomitant use of medications that inhibited or induced antidepressant metabolism increased the overall risk of discontinuation (HR 1.45, 95% CI [1.06, 1.99], p = .020) in a time-dependent analysis. Discussion: We did not detect a significant difference in risk of antidepressant discontinuation rates between males and females even when accounting for cytochrome P450 phenotype. Future studies should account for whether medications that inhibit or induce antidepressant metabolism may be a crucial factor in antidepressant discontinuation.
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- 2023
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7. Medications and Patient Factors Associated With Increased Readmission for Alcohol-Related Diagnoses
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Joseph C. Osborne, II, PharmD, Susan E. Horsman, PharmD, BCPS, Kristin C. Mara, MS, Thomas C. Kingsley, MD, MPH, Robert W. Kirchoff, MD, and Jonathan G. Leung, PharmD, BCPS, BCPP
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Medicine (General) ,R5-920 - Abstract
Objective: To investigate medication factors and patient characteristics associated with readmissions following alcohol-related hospitalizations. Patients and Methods: Adult patients admitted from September 1, 2016, through August 31, 2019, who had an alcohol-related hospitalization were identified through electronic health records. Patient characteristics and medications of interest administered during hospitalization or prescribed at discharge were identified. Medications of interest included US Food and Drug Administration–approved medications for alcohol use disorder, benzodiazepines, barbiturates, gabapentin, opioids, and muscle relaxants. The primary outcome was to identify medications and patient factors associated with 30-day alcohol-related readmission. Secondary outcomes included medications and patient characteristics associated with multiple alcohol-related readmissions within a year from the index admission (ie, two or more readmissions) and factors associated with 30-day all-cause readmission. Results: Characteristics of the 932 patients included in this study associated with a 30-day alcohol-related readmission included younger age, severity of alcohol withdrawal, history of psychiatric disorder, marital status, and the number of prior alcohol-related admission in the previous year. Benzodiazepine or barbiturate use during hospitalization or upon discharge was associated with 30-day alcohol-related readmission (P=.006). Gabapentin administration during hospitalization or upon discharge was not associated with 30-day alcohol-related readmission (P=.079). Conclusion: The findings reinforce current literature identifying patient-specific factors associated with 30-day readmissions. Gabapentin use was not associated with readmissions; however, there was an association with benzodiazepine/barbiturate use.
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- 2022
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8. Comment on: Treatment strategies for clozapine-induced hypotension: A systematic review
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Patrick M. Wieruszewski, Erica D. Wittwer, Sarah B. Leung, and Jonathan G. Leung
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Therapeutics. Pharmacology ,RM1-950 ,Psychiatry ,RC435-571 - Published
- 2022
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9. Assessing Naltrexone Prescribing and Barriers to Initiation for Alcohol Use Disorder: A Multidisciplinary, Multisite Survey
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Jonathan G. Leung, Prasanna P. Narayanan, Matej Markota, Nathaniel E. Miller, Kemuel L. Philbrick, M. Caroline Burton, and Robert W. Kirchoff
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alcohol use disorder ,naltrexone ,prescribing ,substance use disorder ,survey ,Psychiatry ,RC435-571 - Abstract
ObjectiveTo survey barriers in prescribing naltrexone for alcohol use disorder.MethodsA 12-question survey related to naltrexone prescribing patterns, perceptions, and knowledge was sent to 770 prescribers in the departments of internal medicine, family medicine, and psychiatry across a health system with sites in Arizona, Florida, and Minnesota.ResultsResponses were obtained and included for 146/770 prescribers (19.0% response rate). Most respondents were in the department of internal medicine (n = 94, 64.4%), but the departments of psychiatry (n = 22, 15.1%) and family medicine (n = 30, 20.5%) were also represented. Only 34 (23.3%) respondents indicated they had prescribed naltrexone in the previous 3 months. The most common reasons for not prescribing naltrexone were “unfamiliarity with naltrexone for treatment of alcohol use disorder” and “patients do not have appropriate follow-up or are not in a formal treatment program.” Compared with those representing internal/family medicine, psychiatry respondents were more likely to prescribe naltrexone and answer knowledge questions correctly.ConclusionIn this survey among primarily non-addiction-trained prescribers, a disparity was shown for prescribing naltrexone and in knowledge barriers between staff in internal/family medicine and psychiatry. There exist opportunities for education and quality improvement that promote the prescribing of naltrexone for alcohol use disorder by non-addiction specialists.
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- 2022
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10. Retrospective Analysis of Gabapentin for Alcohol Withdrawal in the Hospital Setting: The Mayo Clinic Experience
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Ruth E. Bates, MD, Jonathan G. Leung, PharmD, RPh, Robert J. Morgan, III, MD, Karen M. Fischer, MPH, Kemuel L. Philbrick, MD, and Simon Kung, MD
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Medicine (General) ,R5-920 - Abstract
Objective: To evaluate the efficacy and safety of a fixed-dose gabapentin taper protocol for alcohol withdrawal in hospitalized patients. Patients and Methods: We retrospectively identified patients admitted to the hospital from January 1, 2016, to April 30, 2018, for alcohol withdrawal syndrome. Based on the treatment that patients received, they were divided into the gabapentin, benzodiazepine, and combination treatment groups. The primary outcome was length of stay, defined as time from admission to either discharge or 36 hours with Clinical Institute Withdrawal Assessment (CIWA) score less than 10. Inverse probability of treatment weight was used to account for differences in baseline characteristics between groups. Results: A total of 443 patients met criteria for inclusion (128, 253, and 62 patients in the gabapentin, benzodiazepine, and combination groups, respectively). Baseline characteristics were similar among all groups. The median gabapentin group length of stay was 4.0 hours shorter than the benzodiazepine group (P=.012). Maximum CIWA score was 2.2 points lower in the gabapentin group (P=.003). No statistical differences were noted among safety outcomes, including incidence of seizure, intensive care unit transfer, or delirium tremens. Results were not statistically altered by inverse probability of treatment weight analysis. Conclusion: A fixed-dose gabapentin taper protocol appears to be an effective and safe alternative to CIWA-driven benzodiazepines in patients hospitalized with alcohol withdrawal syndrome, though further research is necessary to define the potential subpopulations that benefit most.
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- 2020
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11. Delayed Signs and Symptoms of Extended Release Guanfacine Overdose in Two Adolescent Patients: Implications of Monitoring on the Psychiatry Unit
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Sanskriti Mishra, Julia Shekunov, Della J. Derscheid, Elizabeth A. Canterbury, and Jonathan G. Leung
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Psychiatry ,RC435-571 - Abstract
Guanfacine is a selective alpha-2a adrenoreceptor agonist that with overdose can cause symptoms ranging from mild sedation to coma, respiratory depression, hyporeflexia, hypotonia, bradycardia, and hypotension. Despite a well-defined and predictable toxidrome, variations can be seen based on multiple factors including age, quantity ingested, organ functions, coingestions, time since ingestion, and specific dosage form. Here, we describe two cases of delayed presentation of extended release guanfacine toxicity and highlight the variations encountered in the toxidrome presentation. These cases bring to attention the importance of maintaining a high suspicion for such atypical presentations, keeping in mind the limitations of managing these complications on an inpatient psychiatric unit.
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- 2022
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12. Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population
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William V. Bobo, Brandon R. Grossardt, Maria I. Lapid, Jonathan G. Leung, Cynthia Stoppel, Paul Y. Takahashi, Robert W. Hoel, Zheng Chang, Christian Lachner, Mohit Chauhan, Lee Flowers, Scott M. Brue, Mark A. Frye, Jennifer St. Sauver, Walter A. Rocca, and Bruce Sutor
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antidepressants ,cohort study ,elderly ,overuse ,prescribing ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract The purpose of this study was to estimate the extent of potential antidepressant overprescribing in a geographically defined U.S. population, and to determine the indications and factors that account for it. We conducted a cohort study of new antidepressant prescriptions for elderly residents of Olmsted County, Minnesota, 2005‐2012, using the Rochester Epidemiology Project medical records‐linkage system. Indications for antidepressants were abstracted from health records for all cohort members. Potential antidepressant overprescribing was defined based on regulatory approval, the level of evidence identified from a standardized drug information database, and multidisciplinary expert review. Predictors of potential antidepressant overprescribing were investigated using logistic regression models, stratified by general antidepressant indication (general medical indication, specific psychiatric diagnosis, and non‐specific psychiatric symptoms). Potential antidepressant overprescribing occurred in 24% of 3199 incident antidepressant prescriptions during the study period, and involved primarily newer antidepressants that were prescribed for non‐specific psychiatric symptoms and subthreshold diagnoses. Potential antidepressant overprescribing was associated with nursing home residence, having a higher number of comorbid medical conditions and outpatient prescribers, taking more concomitant medications, having greater use of urgent or acute care services in the year preceding the index antidepressant prescription, and being prescribed antidepressants via telephone, e‐mail, or patient portal. In conclusion, potential antidepressant overprescribing occurred in elderly persons and involved mainly newer antidepressants used for non‐specific psychiatric symptoms and subthreshold diagnoses, and was associated with indicators of higher clinical complexity or severity and with prescribing without face‐to‐face patient contact.
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- 2019
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13. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms
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Jonathan G. Leung and Brian A. Palmer
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Psychiatry ,RC435-571 - Abstract
One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS). OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of “violent delusions.” However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD) was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient’s obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS.
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- 2016
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14. Paliperidone Palmitate Associated with Necrotizing Deep Tissue Infection and Sepsis Requiring Surgical Intervention
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Jonathan G. Leung, Kirstin J. Kooda, Erin N. Frazee, Sarah Nelson, and Katherine M. Moore
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Psychiatry ,RC435-571 - Abstract
Long-acting injectable antipsychotics provide the delivery of medication over an extended period of time requiring administration typically only every 2 to 4 weeks. The side effect profile of a long-acting injectable antipsychotic is predictable and similar to the oral formulation. However, injection site reactions may occur with this novel delivery system. The risk of an injection site reaction may be greater with the repeated administration of a lipophilic decanoate formulation and include pain, development of indurations, and fibrosis. Severe complications from injection site reactions have rarely been described in the literature with newer agents. We report the first case of a patient prescribed paliperidone palmitate every 3 weeks that developed severe sepsis requiring vasopressors and intubation due to delayed relayed recognition of a necrotizing infection at an injection site. Clinicians should be alerted to screen for injection site reactions when there is an unknown source infection in a patient receiving a long-acting injectable antipsychotic.
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- 2015
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15. Improving clozapine utilization will require continued advocacy, drug sponsor interest, and FDA support to address REMS issues
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Jonathan G Leung, Megan Ehret, Raymond C Love, and Robert O Cotes
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Pharmacology (medical) ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics - Published
- 2023
16. The Modernization of Clozapine
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Jonathan G. Leung, Jose de Leon, Mark A. Frye, Balwinder Singh, Robert O. Cotes, and Susan L. McElroy
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Psychiatry and Mental health ,Pharmacology (medical) - Published
- 2022
17. Iatrogenic clozapine intoxication after hospital admission: A case-based rationale for an inpatient pharmacy clozapine monitoring service
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Jonathan G. Leung, Daniela B. Rakocevic, Shelby N. Courtis, Megan R. Leloux, and Nicholas D. Allen
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Hospitalization ,Pharmacology ,Inpatients ,Iatrogenic Disease ,Humans ,Pharmacology (nursing) ,Pharmacy ,Drug Monitoring ,Hypotension ,Pharmacists ,Pharmacy Service, Hospital ,Clozapine ,Hospitals - Abstract
Clozapine must be retitrated after 2 consecutive days or more of missed doses owing to the risk of severe hypotension, bradycardia, and cardiac arrest. However, other important adverse events such as somnolence, sialorrhea, or respiratory depression can occur without severe cardiovascular sequalae. These other unintended consequences are not well characterized in the literature. Three cases are reported, highlighting the concerns for continuing clozapine without retitration after periods of not taking the medication. Implications are discussed as well as how pharmacists can collaborate with other disciplines to mitigate safety risks associated with clozapine for hospitalized patients.The first case highlights the importance of medication reconciliation and verifying adherence before clozapine continuation in the hospital. Waiting for collateral information and missing one dose are safer than unknowingly resuming clozapine. The second case suggests that it may be safer to consider patients with unexplained worsening psychiatric symptoms as nonadherent and even partially reduced clozapine doses after nonadherence may be unsafe. The final case demonstrates the importance assessing comedications (e.g., warfarin, phenytoin) that have available therapeutic drug monitoring to suggest nonadherence. Each case resulted in significant adverse events requiring transfer to a higher level of care or prolonged hospitalization.Continuation of psychiatric medications when a patient is admitted to the hospital is important to prevent worsening of symptoms. However, assessment of clozapine adherence and confidence in that assessment is crucial to prevent clozapine intoxication, severe hypotension, and even death. Pharmacists are uniquely positioned to assess clozapine adherence and ensure patient safety. A hospital-based service was created at a 2000-bed academic medical center to improve transitions of care when patients are admitted with clozapine. The process was created in collaboration with the psychiatric consultation service. Through this process, pharmacists also complete appropriate hematologic monitoring and ongoing clinical monitoring for adverse events.
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- 2022
18. Medications and Patient Factors Associated With Increased Readmission for Alcohol-Related Diagnoses
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Joseph C. Osborne, Susan E. Horsman, Kristin C. Mara, Thomas C. Kingsley, Robert W. Kirchoff, and Jonathan G. Leung
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Medicine (General) ,R5-920 ,AUD, alcohol use disorder ,AWS, alcohol withdrawal syndrome ,CCI, Charlson comorbidity index ,BMI, body mass index ,Original Article ,AI, artificial intelligence ,CIWA, clinical institute withdrawal assessment ,LOS, length of stay - Abstract
Objective: To investigate medication factors and patient characteristics associated with readmissions following alcohol-related hospitalizations. Patients and Methods: Adult patients admitted from September 1, 2016, through August 31, 2019, who had an alcohol-related hospitalization were identified through electronic health records. Patient characteristics and medications of interest administered during hospitalization or prescribed at discharge were identified. Medications of interest included US Food and Drug Administration–approved medications for alcohol use disorder, benzodiazepines, barbiturates, gabapentin, opioids, and muscle relaxants. The primary outcome was to identify medications and patient factors associated with 30-day alcohol-related readmission. Secondary outcomes included medications and patient characteristics associated with multiple alcohol-related readmissions within a year from the index admission (ie, two or more readmissions) and factors associated with 30-day all-cause readmission. Results: Characteristics of the 932 patients included in this study associated with a 30-day alcohol-related readmission included younger age, severity of alcohol withdrawal, history of psychiatric disorder, marital status, and the number of prior alcohol-related admission in the previous year. Benzodiazepine or barbiturate use during hospitalization or upon discharge was associated with 30-day alcohol-related readmission (P=.006). Gabapentin administration during hospitalization or upon discharge was not associated with 30-day alcohol-related readmission (P=.079). Conclusion: The findings reinforce current literature identifying patient-specific factors associated with 30-day readmissions. Gabapentin use was not associated with readmissions; however, there was an association with benzodiazepine/barbiturate use.
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- 2021
19. Fluctuation between cigarette smoking and use of electronic nicotine delivery systems: Impact on clozapine concentrations and clinical effect
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Daniel J. Montville, Jaclyn M. Lindsey, and Jonathan G. Leung
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medicine.medical_specialty ,Pharmacological management ,Case Reports ,Clinical correlation ,smoking ,Nicotine ,Cigarette smoking ,Internal medicine ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Clozapine ,drug interaction ,clozapine ,business.industry ,CYP450 1A2 ,Drug interaction ,Serum concentration ,Neuropsychology and Physiological Psychology ,Nicotine delivery ,Neurology (clinical) ,business ,cigarettes ,medicine.drug ,nicotine ,electronic nicotine delivery systems - Abstract
Unlike with smoking cigarettes, electronic nicotine delivery systems do not cause CYP450 1A2 induction as there is a lack of combustion and polycyclic aromatic hydrocarbon production. Changing to the use of an electronic nicotine delivery system from cigarettes can result in the deinduction of CYP450 1A2 and the increase of certain medication serum concentrations, including clozapine. A case is reported in which the switch from smoking to an electronic nicotine delivery system resulted in increased clozapine serum concentration and constipation, necessitating pharmacologic management. The patient ultimately transitioned back to cigarettes, which resulted in the emergence of psychiatric symptoms. An evaluation of longitudinal serum concentrations and clinical correlation is provided. It is important that patients and health care professionals have knowledge not only about the impact of smoking cigarettes on clozapine metabolism, but also the effects of switching to or from an electronic nicotine delivery system.
- Published
- 2021
20. Finger capillary blood sampling for ANC monitoring in a pilot clozapine clinic: Another option between venipuncture and emerging point-of-care technology
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Jonathan G. Leung, Kristin C. Mara, Emily K. Johnson, Terri S. Wittenberger, and Kathyrn M. Schak
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Psychiatry and Mental health ,Biological Psychiatry - Published
- 2023
21. Improving the Clozapine Prescribing Information to Enhance Clozapine Safety and Address Barriers: Clozapine-Induced Inflammation, Pnuemonia, and Rems
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Jonathan G, Leung and Ian R, McGrane
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Inflammation ,Humans ,Practice Patterns, Physicians' ,Clozapine ,Antipsychotic Agents - Published
- 2022
22. Assessment of gender differences in letters of recommendation for pharmacy residency applicants
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Kristin C. Mara, Mikhaila L. Rice, Sarah B Leung, and Jonathan G. Leung
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Male ,letters of recommendation ,Pharmacy Residencies ,Sexism ,Word count ,Pharmacy ,implicit bias ,Affect (psychology) ,gender bias ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Gender bias ,Humans ,030212 general & internal medicine ,Personnel Selection ,Pharmacology ,Medical education ,Academic year ,business.industry ,Health Policy ,Significant difference ,Internship and Residency ,Residency program ,Note ,job application ,030220 oncology & carcinogenesis ,AcademicSubjects/MED00410 ,Female ,Psychology ,business - Abstract
Purpose Letters of recommendation (LORs) are highly regarded components of pharmacy residency applications, as they provide insight into an applicant’s character and capabilities. In other medical fields, differences in language have been reported for letters written for female and male applicants; however, data on gender differences in LORs for pharmacy residency applications are currently lacking. Methods LORs for applicants to our institution’s postgraduate year 1 pharmacy residency program for the 2019-2020 academic year were extracted and processed by a natural language processing service. Words within 18 categories were identified and counted for each LOR. Total word count was also compared. Results Of the 473 LORs included for analysis, 320 (67.7%) were written for female applicants and 153 (32.3%) were written for male applicants. Approximately two-thirds of all writers were women for both female and male applicants. In comparing letters for women and men, there was a statistically significant difference in the percentage of LORs that contained terms in categories described as gendered, solitary/reserved, and desire. There was no statistically significant difference in total word count or in the presence of words in other categories such as grindstone, standout, agentic, or communal. When controlling for grade point average, writer gender, duration that the writer knew the applicant, and the writer’s professional position, there were no changes to the statistical findings. Conclusion Letters written for female and male applicants were largely similar with regard to length and word categories utilized. While no clear gender bias was found when evaluating pharmacy residency LORs, writers must continue to assess their implicit biases and how those biases might affect a candidate’s application.
- Published
- 2021
23. Naltrexone Initiation in the Inpatient Setting for Alcohol Use Disorder: A Systematic Review of Clinical Outcomes
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Thomas Kingsley, Jack McHugh, M. Caroline Burton, Norhan M. Mohammed, Matej Markota, Jonathan G. Leung, Robert Kirchoff, and Rahul Chaudhary
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medicine.medical_specialty ,Medicine (General) ,business.industry ,Clinical study design ,Scopus ,PsycINFO ,Alcohol use disorder ,Emergency department ,030204 cardiovascular system & hematology ,medicine.disease ,Naltrexone ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Randomized controlled trial ,law ,medicine ,030212 general & internal medicine ,Medical prescription ,Psychiatry ,business ,medicine.drug - Abstract
Alcohol use disorder (AUD) is a highly prevalent health issue in the United States. The number of those receiving medication-assisted treatment (MAT) is limited, despite strong evidence for their effectiveness. The inpatient setting may represent an important opportunity to initiate MAT. The goal of this study was to summarize the data on naltrexone initiation in the emergency department or inpatient setting for the management of AUDs. We searched ClinicalTrials.gov , Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science from inception through October 31, 2019. Search strategies were created using a combination of keywords ( Supplemental Appendix 1 , available online at http://www.mcpiqojournal.org ) and standardized index terms related to naltrexone therapy for medically hospitalized patients with AUD. Two uncontrolled pre-post study designs evaluated naltrexone prescription rates, 30-day readmission rates, and rehospitalization rates. Two authors independently abstracted data on study characteristics, results, and study-level risk of bias. The research team collaborated to assess the strength of evidence across studies. Two studies reported that implementing a protocol for naltrexone initiation increased MAT rates, with one study noting a substantial decrease in 30-day hospital readmissions. Overall, we found that there is a paucity of data on naltrexone initiation in the inpatient setting for AUDs. This likely reflects the nature of current clinical practice and prescriber comfortability. There is a need for further studies evaluating MAT initiation in the inpatient setting. Furthermore, efforts to increase provider knowledge of these therapeutic options are in need of further exploration.
- Published
- 2021
24. Successful Continuation of Clozapine in Conjunction With Chimeric Antigen Receptor T-Cell (CAR-T) Immunotherapy: Case Report
- Author
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Adrienne Nedved, N. Nora Bennani, Jade L. Kutzke, Heather P. May, Catherine E. DeFino, and Jonathan G. Leung
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,T cell ,medicine.medical_treatment ,Immunotherapy, Adoptive ,Cell therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Clozapine ,Receptors, Chimeric Antigen ,Hematology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Immunotherapy ,medicine.disease ,Chimeric antigen receptor ,Conjunction (grammar) ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Schizophrenia ,Immunology ,Lymphoma, Large B-Cell, Diffuse ,business ,medicine.drug - Published
- 2021
25. Retrospective Analysis of Gabapentin for Alcohol Withdrawal in the Hospital Setting: The Mayo Clinic Experience
- Author
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Kemuel L. Philbrick, Jonathan G. Leung, Ruth E. Bates, Simon Kung, Robert J. Morgan, and Karen M. Fischer
- Subjects
Gabapentin ,medicine.drug_class ,Alcohol use disorder ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,IPTW, inverse probability of treatment weight ,Medicine ,030212 general & internal medicine ,max, maximum ,Delirium tremens ,Benzodiazepine ,lcsh:R5-920 ,AWS, alcohol withdrawal syndrome ,business.industry ,Incidence (epidemiology) ,medicine.disease ,ICU, intensive care unit ,Intensive care unit ,AUD, alcohol use disorder ,Quartile ,Alcohol withdrawal syndrome ,Anesthesia ,CIWA, Clinical Institute Withdrawal Assessment ,Original Article ,business ,lcsh:Medicine (General) ,GABA, γ-aminobutyric acid ,LOS, length of stay ,min, minimum ,Q, quartile ,medicine.drug - Abstract
Objective To evaluate the efficacy and safety of a fixed-dose gabapentin taper protocol for alcohol withdrawal in hospitalized patients. Patients and Methods We retrospectively identified patients admitted to the hospital from January 1, 2016, to April 30, 2018, for alcohol withdrawal syndrome. Based on the treatment that patients received, they were divided into the gabapentin, benzodiazepine, and combination treatment groups. The primary outcome was length of stay, defined as time from admission to either discharge or 36 hours with Clinical Institute Withdrawal Assessment (CIWA) score less than 10. Inverse probability of treatment weight was used to account for differences in baseline characteristics between groups. Results A total of 443 patients met criteria for inclusion (128, 253, and 62 patients in the gabapentin, benzodiazepine, and combination groups, respectively). Baseline characteristics were similar among all groups. The median gabapentin group length of stay was 4.0 hours shorter than the benzodiazepine group (P=.012). Maximum CIWA score was 2.2 points lower in the gabapentin group (P=.003). No statistical differences were noted among safety outcomes, including incidence of seizure, intensive care unit transfer, or delirium tremens. Results were not statistically altered by inverse probability of treatment weight analysis. Conclusion A fixed-dose gabapentin taper protocol appears to be an effective and safe alternative to CIWA-driven benzodiazepines in patients hospitalized with alcohol withdrawal syndrome, though further research is necessary to define the potential subpopulations that benefit most.
- Published
- 2020
26. Predatory Journals: A Cautionary Tale and a Lesson in Copyright Transfer
- Author
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LeAnn Stee, Patrick M. Wieruszewski, Jonathan G. Leung, Christopher R. Takala, and Brian A. Palmer
- Subjects
Publishing ,MEDLINE ,General Medicine ,Video-Audio Media ,Authorship ,United States ,World Wide Web ,Open Access Publishing ,Copyright ,Political science ,Humans ,Periodicals as Topic ,Editorial Policies - Published
- 2020
27. Thrombocytopenia associated with clonidine in a case of clozapine-induced sialorrhea
- Author
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Kathryn M. Schak, Jade L. Kutzke, Robert J. Morgan, and Jonathan G. Leung
- Subjects
drug safety ,Sedation ,thrombocytopenia ,Schizoaffective disorder ,Case Reports ,Aspiration pneumonia ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,sialorrhea ,clonidine ,Adverse effect ,Clozapine ,Sialorrhea ,clozapine ,business.industry ,medicine.disease ,030227 psychiatry ,Clonidine ,Neuropsychology and Physiological Psychology ,Schizophrenia ,Anesthesia ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Clozapine is approved by the US Food and Drug Administration for treatment-resistant schizophrenia and mitigation of suicidality in patients with schizophrenia or schizoaffective disorder. Clozapine requires monitoring of adverse events, such as hypotension, myocarditis, cardiomyopathy, seizures, severe neutropenia, and gastrointestinal hypomotility. Sialorrhea is another adverse event that can be bothersome for patients and result in nonadherence or the development of aspiration pneumonia. Clonidine, an α2A adrenergic receptor agonist, is one medication option that can reduce or eliminate sialorrhea. Clonidine is generally well tolerated but can contribute to hypotension and sedation. One adverse event associated with clonidine not described in the literature is thrombocytopenia. Reported is a case of clonidine-associated thrombocytopenia when used for the treatment of clozapine-induced sialorrhea.
- Published
- 2020
28. Correction: An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
- Author
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Jose de Leon, Georgios Schoretsanitis, Robert L. Smith, Espen Molden, Anssi Solismaa, Niko Seppälä, Miloslav Kopeček, Patrik Švancer, Ismael Olmos, Carina Ricciardi, Celso Iglesias-Garcia, Ana Iglesias-Alonso, Edoardo Spina, Can-Jun Ruan, Chuan-Yue Wang, Gang Wang, Yi-Lang Tang, Shih-Ku Lin, Hsien-Yuan Lane, Yong Sik Kim, Se Hyun Kim, Anto P. Rajkumar, Dinora F. González-Esquivel, Helgi Jung-Cook, Trino Baptista, Christopher Rohde, Jimmi Nielsen, Hélène Verdoux, Clelia Quiles, Emilio J. Sanz, Carlos De Las Cuevas, Dan Cohen, Peter F.J. Schulte, Aygün Ertuğrul, A. Elif Anıl Yağcıoğlu, Nitin Chopra, Betsy McCollum, Charles Shelton, Robert O. Cotes, Arun R. Kaithi, John M. Kane, Saeed Farooq, Chee H. Ng, John Bilbily, Christoph Hiemke, Carlos López-Jaramillo, Ian McGrane, Fernando Lana, Chin B. Eap, Manuel Arrojo-Romero, Flavian Ş. Rădulescu, Erich Seifritz, Susanna Every-Palmer, Chad A. Bousman, Emmanuel Bebawi, Rahul Bhattacharya, Deanna L. Kelly, Yuji Otsuka, Judit Lazary, Rafael Torres, Agustin Yecora, Mariano Motuca, Sherry K.W. Chan, Monica Zolezzi, Sami Ouanes, Domenico De Berardis, Sandeep Grover, Ric M. Procyshyn, Richard A. Adebayo, Oleg O. Kirilochev, Andrey Soloviev, Konstantinos N. Fountoulakis, Alina Wilkowska, Wiesław J. Cubała, Muhammad Ayub, Alzira Silva, Raphael M. Bonelli, José M. Villagrán-Moreno, Benedicto Crespo-Facorro, Henk Temmingh, Eric Decloedt, Maria R. Pedro, Hiroyoshi Takeuchi, Masaru Tsukahara, Gerhard Gründer, Marina Sagud, Andreja Celofiga, Dragana Ignjatovic Ristic, Bruno B. Ortiz, Helio Elkis, António J. Pacheco Palha, Adrián LLerena, Emilio Fernandez-Egea, Dan Siskind, Abraham Weizman, Rim Masmoudi, Shamin Mohd Saffian, Jonathan G. Leung, Peter F. Buckley, Stephen R. Marder, Leslie Citrome, Oliver Freudenreich, Christoph U. Correll, Daniel J. Müller, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Psychiatry and Mental health ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Pharmacology (medical) ,General Medicine - Published
- 2022
29. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
- Author
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Jose de Leon, Georgios Schoretsanitis, Robert L. Smith, Espen Molden, Anssi Solismaa, Niko Seppälä, Miloslav Kopeček, Patrik Švancer, Ismael Olmos, Carina Ricciardi, Celso Iglesias-Garcia, Ana Iglesias-Alonso, Edoardo Spina, Can-Jun Ruan, Chuan-Yue Wang, Gang Wang, Yi-Lang Tang, Shih-Ku Lin, Hsien-Yuan Lane, Yong Sik Kim, Se Hyun Kim, Anto P. Rajkumar, Dinora F. González-Esquivel, Helgi Jung-Cook, Trino Baptista, Christopher Rohde, Jimmi Nielsen, Hélène Verdoux, Clelia Quiles, Emilio J. Sanz, Carlos De Las Cuevas, Dan Cohen, Peter F.J. Schulte, Aygün Ertuğrul, A. Elif Anıl Yağcıoğlu, Nitin Chopra, Betsy McCollum, Charles Shelton, Robert O. Cotes, Arun R. Kaithi, John M. Kane, Saeed Farooq, Chee H. Ng, John Bilbily, Christoph Hiemke, Carlos López-Jaramillo, Ian McGrane, Fernando Lana, Chin B. Eap, Manuel Arrojo-Romero, Flavian Ş. Rădulescu, Erich Seifritz, Susanna Every-Palmer, Chad A. Bousman, Emmanuel Bebawi, Rahul Bhattacharya, Deanna L. Kelly, Yuji Otsuka, Judit Lazary, Rafael Torres, Agustin Yecora, Mariano Motuca, Sherry K.W. Chan, Monica Zolezzi, Sami Ouanes, Domenico De Berardis, Sandeep Grover, Ric M. Procyshyn, Richard A. Adebayo, Oleg O. Kirilochev, Andrey Soloviev, Konstantinos N. Fountoulakis, Alina Wilkowska, Wiesław J. Cubała, Muhammad Ayub, Alzira Silva, Raphael M. Bonelli, José M. Villagrán-Moreno, Benedicto Crespo-Facorro, Henk Temmingh, Eric Decloedt, Maria R. Pedro, Hiroyoshi Takeuchi, Masaru Tsukahara, Gerhard Gründer, Marina Sagud, Andreja Celofiga, Dragana Ignjatovic Ristic, Bruno B. Ortiz, Helio Elkis, António J. Pacheco Palha, Adrián LLerena, Emilio Fernandez-Egea, Dan Siskind, Abraham Weizman, Rim Masmoudi, Shamin Mohd Saffian, Jonathan G. Leung, Peter F. Buckley, Stephen R. Marder, Leslie Citrome, Oliver Freudenreich, Christoph U. Correll, and Daniel J. Müller
- Subjects
Adult ,Male ,CYP1A2 ,mortality/drug effects ,clozapine/therapeutic use ,American continental ancestry group ,Asian continental ancestry group ,clozapine/adverse effects ,clozapine/blood ,clozapine/metabolism ,clozapine/toxicity ,drug labeling ,European continental ancestry group ,infection ,inflammation ,Native ,sex ,smoking ,Asian People ,Humans ,Pharmacology (medical) ,Clozapine ,Valproic Acid ,Native - American continental ancestry group - Asian continental ancestry group - clozapine/adverse effects - clozapine/blood - clozapine/metabolism - clozapine/therapeutic use - clozapine/toxicity - CYP1A2 - drug labeling - European continental ancestry group - infection - inflammation - mortality/drug effects - sex - smoking ,General Medicine ,Psychiatry and Mental health ,C-Reactive Protein ,Female ,Antipsychotic Agents - Abstract
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
- Published
- 2021
30. PRN OPINION PAPER: Application of precision medicine across pharmacy specialty areas
- Author
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Maria Sheridan, Jimmi Hatton Kolpek, Jason H. Karnes, Kara L. Birrer, Christine M. Formea, Rebecca Pulk, Jonathan G. Leung, Janna Afanasjeva, Molly G. Minze, Elias B. Chahine, Chasity M. Shelton, Lamis R. Karaoui, Christopher R. Ensor, Eglis Tellez-Corrales, Christine M. Walko, James C. Lee, Angela Q. Maldonado, Keri C. Anderson, Erin F. Barreto, Jomy M. George, Roseann S. Gammal, Shubha Bhat, Craig J. Beavers, Stephanie A. Flowers, Mary F. Hebert, Kelly E. Caudle, Michael A. Smith, Scott A Soefje, Larisa H. Cavallari, and Rena A. Gosser
- Subjects
medicine.medical_specialty ,business.industry ,Pharmacogenomics ,Specialty ,medicine ,Pharmaceutical Science ,Pharmacology (medical) ,Medical physics ,Pharmacy ,Precision medicine ,business - Published
- 2019
31. Pharmacologic Management of Status Epilepticus
- Author
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Erin D Wieruszewski, Patrick M. Wieruszewski, Jonathan G. Leung, and Caitlin S. Brown
- Subjects
medicine.medical_specialty ,business.industry ,Pharmacological management ,MEDLINE ,General Medicine ,Status epilepticus ,Critical Care Nursing ,Text mining ,Status Epilepticus ,Emergency Medicine ,medicine ,Humans ,Anticonvulsants ,medicine.symptom ,Intensive care medicine ,business - Published
- 2020
32. Improvement of Inpatient Psychiatric Facility Quality Reporting program measure: Screening for metabolic disorders through pharmacy collaborative practice agreement
- Author
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Michelle Kreps, Melinda Dively-White, Kendra K. Anderson, Amanda C. Owen, Kathryn M. Schak, Andrew J Webb, Emily K. Johnson, and Jonathan G. Leung
- Subjects
medicine.medical_specialty ,Quality management ,medicine.medical_treatment ,Pharmacist ,Psychological intervention ,Pharmacology (nursing) ,Pharmacy ,Medicare ,Pharmacists ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Extrapyramidal symptoms ,medicine ,Humans ,030212 general & internal medicine ,Antipsychotic ,Aged ,Pharmacology ,Inpatients ,business.industry ,United States ,Clinical pharmacy ,Pharmaceutical Services ,Emergency medicine ,medicine.symptom ,business ,Medicaid - Abstract
Background Second-generation antipsychotics are associated with lower risks of extrapyramidal symptoms, including tardive dyskinesia. However, many second-generation antipsychotics are associated with metabolic adverse effects, including weight gain, impaired blood glucose control, and hyperlipidemia. Metabolic monitoring for patients prescribed antipsychotic medication is 1 of several measures of the Centers for Medicare & Medicaid Services’ Inpatient Psychiatric Facility Quality Reporting program. Screening for metabolic disorders (SMD) must be obtained within the previous 365 days before the hospital discharge date. National data suggest that compliance with this measure is low. Objective To improve compliance of metabolic monitoring by 20% while ensuring that the quality improvement interventions did not cause any unintended adverse effects on other aspects of our system. Practice description This quality initiative was conducted at a large, 2000-bed academic medical center with approximately 80 inpatient psychiatric beds. Practice innovation: To improve the metabolic screening rates, a pharmacist collaborative practice agreement (CPA) was established as part of a quality improvement project. Previously, there were no formal processes at the institution to ensure that appropriate laboratory tests were conducted. Evaluation methods Using an uncontrolled before-and-after design, SMD data were gathered from 6 months before and 6 months after CPA implementation. Pearson chi-square test or Fisher exact test were used to compare the pre- and postintervention groups in this quasi-experimental design. Results Compared with the preintervention period, compliance of SMD monitoring increased by 21.2% in the postintervention phase—from 69.2% to 90.4% (P Conclusion The empowerment of clinical pharmacists with a CPA significantly improved guideline-concordant metabolic monitoring of antipsychotics. These findings may have significant impact on the approach to the safe use of these essential psychotropic medications and provide a framework for other inpatient mental health facilities to optimally use the skills of their interdisciplinary team.
- Published
- 2020
33. Second-Generation Antipsychotics and Pneumonia-Related Hospitalizations
- Author
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Jonathan G. Leung, Daniel C. DeSimone, Bryce M. Kayhart, Kristin C. Mara, Robert J. Morgan, and Victoria R. Milano
- Subjects
Adult ,Male ,Risk ,Olanzapine ,medicine.medical_specialty ,Bipolar Disorder ,Schizoaffective disorder ,Internal medicine ,medicine ,Humans ,Bipolar disorder ,Clozapine ,Aged ,Retrospective Studies ,Risperidone ,business.industry ,Retrospective cohort study ,Pneumonia ,General Medicine ,Middle Aged ,medicine.disease ,Hospitalization ,Psychotic Disorders ,Schizophrenia ,Quetiapine ,Female ,business ,Antipsychotic Agents ,medicine.drug - Abstract
Objective To compare the rate of hospitalizations for pneumonia in patients with a psychotic or bipolar disorder who were prescribed 1 of 4 second-generation antipsychotics prior to admission. Methods This retrospective cohort study included patients who were medically admitted for pneumonia to a 2,059-bed academic medical center or its associated health system hospital. Medical records of 872 admissions from November 1, 2016 to December 15, 2018, were included for all adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder prescribed clozapine, olanzapine, quetiapine, or risperidone prior to admission. Results There was no significantly increased risk of pneumonia for patients taking olanzapine (odds ratio [OR] = 1.08, 95% CI, 0.48-2.41) or quetiapine (OR = 0.97, 95% CI, 0.42-2.25) prior to admission compared to risperidone. When controlling for various factors, treatment with a combination of antipsychotics including clozapine (OR = 2.28, 95% CI, 1.13-4.62, P = .022) and clozapine alone (OR = 2.37, 95% CI, 1.30-4.32, P = .005) was associated with an increased risk of pneumonia-related hospitalization compared to treatment with risperidone, olanzapine, or quetiapine alone. Conclusions The findings of this study in combination with other published literature support an association of an increased risk of pneumonia with the use of clozapine, although this cannot be interpreted as causal. These data show that use of clozapine alone or in combination with other antipsychotics significantly increases risk of pneumonia, although this finding cannot be deemed causal due to study design.
- Published
- 2020
34. Clozapine treated patients and COVID-19: Ensuring continued care through collaboration
- Author
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Jonathan G. Leung, Kathryn M. Schak, and Terri S. Wittenberger
- Subjects
2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Pharmacist ,MEDLINE ,Pharmacists ,Article ,Physicians ,Pandemic ,medicine ,Humans ,REMS ,Intensive care medicine ,Clozapine ,Intersectoral Collaboration ,Pandemics ,Biological Psychiatry ,business.industry ,COVID-19 ,Psychiatry and Mental health ,Drug Monitoring ,business ,Coronavirus Infections ,medicine.drug ,Antipsychotic Agents - Published
- 2020
35. Pharmacogenetic testing in psychiatric inpatients with polypharmacy is associated with decreased medication side effects but not via medication changes
- Author
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Jacqueline T. Ho, Emily K. Johnson, Simon Kung, Jonathan G. Leung, Maria I. Lapid, Jessica A. Wright, Andrea R. Collins, and Kristina C. Dammen
- Subjects
Adult ,CYP2D6 ,medicine.medical_specialty ,Side effect ,Drug-Related Side Effects and Adverse Reactions ,CYP2C19 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Medical prescription ,Psychiatry ,Biological Psychiatry ,Polypharmacy ,Inpatients ,business.industry ,Checklist ,030227 psychiatry ,Pharmacogenomic Testing ,Psychiatry and Mental health ,Pharmacogenetics ,Clinical Global Impression ,business ,030217 neurology & neurosurgery - Abstract
In psychiatric patients, medication adverse effects are regularly attributed to psychosomatic causes. However, many psychotropic medications are metabolized by cytochrome P450 (CYP450) enzymes. In the setting of polypharmacy, the activity of these enzymes may produce unfavorable drug-drug interactions (DDI) and drug-genotype interactions (DGI) that contribute to morbidity and mortality. This study sought to estimate the risk of adverse DDI and DGI in psychiatric inpatients with polypharmacy. We assessed whether medication changes made after pharmacogenetics (PGx) testing correlated with changes in side effects and overall improvement. Adult psychiatry inpatients with polypharmacy, defined as 5 or more scheduled prescription medications, completed the 24-item Antidepressant Side Effect Checklist (ASEC) questionnaire on enrollment and underwent PGx testing. Analysis of PGx results focused on whether the CYP2D6 and CYP2C19 phenotypes were “extreme,” defined as poor, poor to intermediate, or ultrarapid. Approximately 30 days after PGx results were sent to outpatient providers, patients were contacted to obtain their current medication list and ASEC and Clinical Global Impression Improvement (CGI-I) scores. A total of 80 patients were enrolled, and 52 (65%) completed follow-up. ASEC scores improved from 11.5 (±8.1) to 7.2 (±6.0) (p = 0.0009). Mean CGI-I score was 2.7 (±1.4), between “minimal” to “much improved.” However, linear regression revealed that these improvements were not correlated with whether medications were changed. We concluded that the impact of drug-genotype interactions in this small sample of inpatients with polypharmacy was low, and that patient improvement was related not to PGx-guided medication changes but to other treatments during hospitalization.
- Published
- 2020
36. Use of a Gabapentin Protocol for the Management of Alcohol Withdrawal: A Preliminary Experience Expanding From the Consultation-Liaison Psychiatry Service
- Author
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Bruno A. Perossa, Nicholas D. Allen, Daniel K. Hosker, Daniela B. Rakocevic, Hannah K. Betcher, Ross A. Dierkhising, Jonathan G. Leung, Kristin L. Borreggine, Blaine A. Minton, Benjamin R. Braus, Elliot M. Handler, Amy L. Stark, and Kemuel L. Philbrick
- Subjects
Male ,medicine.medical_specialty ,Gabapentin ,medicine.drug_class ,Craving ,Alcohol ,Drug Administration Schedule ,Benzodiazepines ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sobriety ,Arts and Humanities (miscellaneous) ,medicine ,Humans ,030212 general & internal medicine ,Prospective cohort study ,Applied Psychology ,Benzodiazepine ,Ethanol ,business.industry ,Middle Aged ,medicine.disease ,Substance Withdrawal Syndrome ,Psychiatry and Mental health ,Treatment Outcome ,chemistry ,Alcohol withdrawal syndrome ,Emergency medicine ,Liaison psychiatry ,Female ,medicine.symptom ,business ,Excitatory Amino Acid Antagonists ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Benzodiazepines are the conventional mainstay to manage alcohol withdrawal; however, patients are subsequently at increased risk for poor sleep, cravings, and return to drinking. Research on alternative pharmacologic agents to facilitate safe alcohol withdrawal is scant. Gabapentin is one medication shown in small studies to reduce the need for benzodiazepines in the setting of alcohol withdrawal. The continuation of gabapentin after alcohol withdrawal appears to be safe during early sobriety and may aid in reducing alcohol-related cravings or returning to alcohol consumption. Use of a gabapentin-based, benzodiazepine-sparing protool began in early 2015 by the Mayo Clinic, Rochester, Consultation-Liaison Psychiatry Service. Objective A retrospective chart review was conducted to detect any safety concerns with use of a gabapentin protocol for alcohol withdrawal syndrome. Methods Secondary outcomes were derived by comparing a matched cohort of patients who received benzodiazepines for alcohol withdrawal syndrome. Results Seventy-seven patients had their alcohol withdrawal managed via a gabapentin protocol during the study period. No patients required transfer to a higher level of care or had a documented withdrawal seizure. Length of stay between the gabapentin protocol group and benzodiazepine group were similar. Conclusion This preliminary data has supported the frequent use of this protocol in the general internal medicine practice and formalization of an institutional order set of this protocol for mild to moderate alcohol withdrawal syndrome. Prospective studies are required to validate findings.
- Published
- 2018
37. Clozapine-induced cardiomyopathy and myocarditis monitoring: A systematic review
- Author
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Kathryn M. Schak, Amanda C. Owen, Jonathan G. Leung, Robert J. Morgan, Kristen N. Knoph, Brian A. Palmer, Mayur Patel, and Megan R. Leloux
- Subjects
medicine.medical_specialty ,Myocarditis ,medicine.medical_treatment ,Cardiomyopathy ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Antipsychotic ,Adverse effect ,Intensive care medicine ,Clozapine ,Biological Psychiatry ,Monitoring, Physiologic ,biology ,business.industry ,medicine.disease ,Troponin ,030227 psychiatry ,Psychiatry and Mental health ,Systematic review ,Schizophrenia ,biology.protein ,medicine.symptom ,Cardiomyopathies ,business ,030217 neurology & neurosurgery ,Antipsychotic Agents ,medicine.drug - Abstract
The use of clozapine requires monitoring the absolute neutrophil count because of the risk of agranulocytosis, but other potentially fatal adverse events associated with clozapine (specifically, myocarditis and cardiomyopathy) do not have mandatory procedures. We performed a systematic review of English-language articles to synthesize an evidence-based approach for myocarditis and cardiomyopathy monitoring. Articles published from January 1988 through February 2017 were identified through a search of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Google Scholar. Selected articles were required to relate to myocarditis or cardiomyopathy in humans from exposure to clozapine. A total of 144 articles were included. Recommendations varied widely. Some authors recommended baseline laboratory monitoring, with or without follow-up testing, for C-reactive protein, creatine kinase MB, and troponin. Electrocardiography was commonly recommended, and echocardiography was less commonly recommended. The expense of monitoring was a consideration. A unanimous recommendation was to stop the use of clozapine and seek a cardiovascular consultation if myocarditis or cardiomyopathy is suspected. Although there is general agreement on which tests to perform for confirming myocarditis and cardiomyopathy, preemptive screening for these clozapine-induced conditions is controversial, and cost and barriers for the use of clozapine are concerns. For asymptomatic patients receiving clozapine, testing could include baseline electrocardiography, echocardiography as part of a cardiac consultation if patients have cardiac disease or risk factors, and monitoring of C-reactive protein and troponin as indicated.
- Published
- 2018
38. A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults
- Author
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Sarah Nelson, Julie L. Cunningham, Maria I. Lapid, Jonathan G. Leung, Virginia H. Thompson, and Bryce M. Kayhart
- Subjects
Adult ,Male ,medicine.medical_specialty ,Palliative care ,Nausea ,medicine.medical_treatment ,Administration, Cutaneous ,Quetiapine Fumarate ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Humans ,Dementia ,Antipsychotic ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Hospice and palliative medicine ,030220 oncology & carcinogenesis ,Anesthesia ,Quetiapine ,Female ,Nasal administration ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Antipsychotic Agents ,medicine.drug - Abstract
In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.
- Published
- 2018
39. Concurrent Electroconvulsive Therapy and Bupropion Treatment
- Author
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Brian A. Palmer, Lauren Murphy, Jonathan G. Leung, Christopher R. Takala, and Jennifer R. Geske
- Subjects
Adult ,Male ,medicine.drug_class ,medicine.medical_treatment ,Neuroscience (miscellaneous) ,Electroencephalography ,behavioral disciplines and activities ,03 medical and health sciences ,0302 clinical medicine ,Electroconvulsive therapy ,Seizures ,mental disorders ,Humans ,Medicine ,Dosing ,Electroconvulsive Therapy ,Bupropion ,Aged ,Retrospective Studies ,Depressive Disorder, Major ,Benzodiazepine ,Seizure threshold ,medicine.diagnostic_test ,business.industry ,Mental Disorders ,Retrospective cohort study ,Middle Aged ,Combined Modality Therapy ,030227 psychiatry ,Psychiatry and Mental health ,Case-Control Studies ,Concomitant ,Anesthesia ,Antidepressive Agents, Second-Generation ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Bupropion is associated with a dose-dependent increased risk of seizures. Use of concomitant bupropion and electroconvulsive therapy (ECT) remains controversial because of an increased risk of prolonged seizures. This is the first systematic evaluation of the effect of bupropion on ECT. Methods A case group (n = 119), patients treated with concomitant ECT and bupropion, was compared with an age and gender frequency-matched control group (n = 261), treated with only ECT. Electroconvulsive therapy treatment data including seizure length, number of treatments, and concurrent medications were extracted. Longitudinal mixed models examined ECT versus ECT + bupropion group differences over the course of treatments measured by seizure duration (electroencephalogram [EEG] and motor). Multivariable models examined the total number of treatments and first and last seizure duration. All models considered group differences with ECT treatment measures adjusted for age, gender, benzodiazepine treatment, lead placement, and setting. Results Electroconvulsive therapy treatment with bupropion led to shorter motor seizure duration (0.047) and EEG seizure duration (P = 0.001). The number of ECT treatments (7.3 vs 7.0 treatments; P = 0.23), respectively, or the probability of a prolonged seizure (P = 0.15) was not significantly different. Benzodiazepine use was significantly more common in control subjects (P = 0.01). Limitations This is a retrospective analysis limited in part by unavailable variables (seizure threshold, nature of EEG and motor seizure monitoring, type of ECT device, dosing and formulation of bupropion, and duration of the current depressive illness). Conclusions This study revealed a significantly shorter duration in seizure length with ECT + concomitant bupropion, but not in the number of required treatments in those treated compared with ECT without bupropion. There remains a critical need to reevaluate the efficacy of concomitant use of psychotropic medications + ECT.
- Published
- 2017
40. Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine
- Author
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M. Earth Hasassri, Robert J. Morgan, Jason N. Barreto, Sarah Nelson, and Jonathan G. Leung
- Subjects
Lung Diseases ,Male ,medicine.medical_specialty ,Gastrointestinal Diseases ,Minnesota ,medicine.medical_treatment ,Schizoaffective disorder ,Comorbidity ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,medicine ,Humans ,Intensive care medicine ,Antipsychotic ,Adverse effect ,Clozapine ,Applied Psychology ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,030227 psychiatry ,Hospitalization ,Psychiatry and Mental health ,Pneumonia ,Schizophrenia ,Emergency medicine ,Female ,business ,030217 neurology & neurosurgery ,Antipsychotic Agents ,medicine.drug - Abstract
Background Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia; however, rigorous monitoring is required to prevent or detect adverse drug events that contribute to morbidity and mortality. In addition to the Food and Drug Administration (FDA) boxed safety warnings specific to clozapine (agranulocytosis, hypotension, seizures, and cardiomyopathy/myocarditis), other adverse events such as pneumonia and gastrointestinal hypomotility have been reported in the literature to result in hospitalization. Objective To explore the reasons for medical hospitalization in patients prescribed clozapine, a retrospective chart review was completed. Methods Adults with schizophrenia or schizoaffective disorder prescribed clozapine were identified if they had a nonpsychiatric medical admission between 1/1/2003 and 8/1/2015. Demographics, admitting diagnosis, admitting service type, psychiatric consult information, clozapine dosing, and drug interactions were collected. Results Overall, 104 patients, representing 248 hospitalizations, were admitted to a medical unit during the study period. The predominant admission types were for the management of either pulmonary (32.2%) or gastrointestinal (19.8%) illnesses. The most common pulmonary diagnosis was pneumonia, accounting for 58% of pulmonary admissions. Further, 61.2% of the gastrointestinal admissions were related to hypomotility, ranging from constipation to death. Clozapine was discontinued owing to neutropenia in 2 patients; however, in both cases concomitant chemotherapy had been given. Conclusion In patients prescribed clozapine admitted to nonpsychiatric medical settings, gastrointestinal and pulmonary illnesses were common, but not illnesses related to boxed warnings. Additional research is needed to better assess the causality and true incidence of gastrointestinal or pulmonary events associated with clozapine. Furthermore, clinicians must be prepared to prevent, detect, and manage potentially life-threatening events associated with clozapine.
- Published
- 2017
41. Increasing the Safety of Clozapine Management in Hospitalized Patients With or Without Infection: Still Much to Learn … and Teach
- Author
-
Jonathan G. Leung
- Subjects
medicine.medical_specialty ,business.industry ,Hospitalized patients ,medicine.disease ,030226 pharmacology & pharmacy ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Schizophrenia ,Medicine ,business ,Intensive care medicine ,Applied Psychology ,Clozapine ,medicine.drug - Published
- 2018
42. The professional sabbatical: A systematic review and considerations for the health-system pharmacist
- Author
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Erin F. Barreto, Julie L. Cunningham, Jonathan G. Leung, Sarah Nelson, and Leslie C. Hassett
- Subjects
Medical education ,education ,05 social sciences ,Professional development ,Pharmacist ,Staffing ,Pharmaceutical Science ,Pharmacy ,CINAHL ,PsycINFO ,Pharmacists ,030210 environmental & occupational health ,Job Satisfaction ,03 medical and health sciences ,Leadership ,0302 clinical medicine ,Systematic review ,0502 economics and business ,Humans ,Job satisfaction ,Pharmacy research ,Psychology ,health care economics and organizations ,050203 business & management - Abstract
Background Sabbaticals are considered a professional development experience meant to foster growth and revitalize careers. The personal accounts of sabbaticals among medical professionals indicate high value from this experience. Benefits seen at the institutional and individual level include, but are not limited to, reduced burnout and increased job retention. Staffing issues, determining eligibility, and justifying time utilized may be just some barriers to implementing a sabbatical program accessible to the health-system pharmacist. In the literature, there is a dearth of information related to sabbaticals granted to the health-system pharmacist. However, many published experiences of nurses and physicians exist. Objectives A systematic review was performed to synthesize a qualitative yet evidence-based summary of information regarding sabbaticals. The primary aim of this review was to assess the reported benefits and prohibitive factors of taking a sabbatical as it may apply to the health-system pharmacist. Methods Three hundred twenty-eight English-language articles were identified through searching Ovid Medline, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and Scopus from database inception through December 6, 2019. Results A total of 172 articles consisting of studies, descriptions of institutional processes, individual accounts, editorials and letters to the editor, and review articles were included in this systematic review. Rejuvenation and new perspectives/skills to bring back to practice should be regarded as important benefits by institutional/departmental leadership as well as the benefits of reduced turnover and improved job satisfaction. Numerous barriers to completing a sabbatical can be overcome with proper planning. Conclusion This review provides limited insight into benefits and barriers to taking sabbaticals and serves as a basis for health-system pharmacy departments to consider initiating a program if one is not currently in place. Mini-sabbaticals may allow the health-system pharmacist to take a professional time away. Corollaries are drawn between a longitudinal pharmacy research award granted at Mayo Clinic – Rochester and ideas are provided for clinical or educational sabbaticals. It is clear that health-system pharmacy-specific information is lacking, and pharmacy department leadership should be encouraged to continue to share experiences of sabbaticals and outcomes.
- Published
- 2019
43. Prescribing Practices for Patients With Borderline Personality Disorder During Psychiatric Hospitalizations
- Author
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Jonathan G. Leung, Brian A. Palmer, Jennifer L. Vande Voort, Beth R. Larrabee, Magdalena Romanowicz, and Kathryn M. Schak
- Subjects
Polypharmacy ,medicine.medical_specialty ,Psychotropic Drugs ,Evidence-based practice ,medicine.disease ,Rate ratio ,030227 psychiatry ,Hospitalization ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,0302 clinical medicine ,Mood ,Borderline Personality Disorder ,Acute care ,medicine ,Humans ,Medical prescription ,Psychiatry ,Psychology ,Borderline personality disorder ,Psychosocial ,030217 neurology & neurosurgery ,Antipsychotic Agents - Abstract
This study aimed to understand prescribing practices during acute psychiatric hospitalization in a large cohort of patients (N = 569) with borderline personality disorder (BPD) at a tertiary care psychiatry unit from January 1, 2013, through January 1, 2015. The mean number of hospitalizations per patient was 1.5 (range, 1–7). The odds of being prescribed antidepressants, antipsychotics, mood stabilizers, hypnotics, or anxiolytics were higher at discharge than at admission. The rate of psychotropic prescriptions was also higher at discharge than at admission (incidence rate ratio, 1.9). This pattern was true for the combined psychotropic and nonpsychotropic (“medical”) prescriptions. Further guidelines are needed regarding optimal psychosocial, medical, and psychopharmacological care of patients with BPD during acute psychiatric hospitalizations.
- Published
- 2019
44. Mirtazapine for Symptomatic Relief on a Psychiatric Consultation Service: A Case Series
- Author
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Keith G. Rasmussen, Hannah K. Betcher, Kemuel L. Philbrick, Jacob J. Wilson, Jonathan G. Leung, Eliza M. Sukiennik, Daniel K. Hosker, Blaine A. Minton, Nicholas D. Allen, and Kristin L. Borreggine
- Subjects
Adult ,Male ,medicine.medical_specialty ,Nausea ,Sedation ,Mirtazapine ,Pain ,Mianserin ,Antidepressive Agents, Tricyclic ,03 medical and health sciences ,Psychiatric comorbidity ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Sleep Initiation and Maintenance Disorders ,Chart review ,Humans ,Medicine ,Psychiatry ,Adverse effect ,Referral and Consultation ,Applied Psychology ,Aged ,Retrospective Studies ,business.industry ,Middle Aged ,Symptomatic relief ,Anorexia ,Hospitalization ,Psychiatry and Mental health ,Psychiatric consultation ,030220 oncology & carcinogenesis ,Emergency medicine ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background With a complex pharmacologic profile, mirtazapine may promote sleep, stimulate appetite, improve nausea, and reduce pain. Some practitioners working on the Mayo Clinic inpatient psychiatric consultation/liaison service have recommended mirtazapine in medically ill patients with or without formal psychiatric comorbidity to target these symptoms. Objective To assess the success of this practice, we conducted a retrospective chart review covering a 4.5-year period. Methods For patients recommended to start mirtazapine, global improvement in specific symptoms and suspected side effects were recorded. Results During the study period, 528 medically ill patients started mirtazapine following a recommendation from the psychiatric consultation service. In total, 475 patients were provided mirtazapine to specifically target sleep, nausea, pain, or appetite. There was documented improvement in these symptoms for 37.7%, 37.0%, 36.4%, and 23.5% of the patients, respectively. These rates of improvement are conservative for the 229 patients without documented response, i.e., 48% of the patients who were given the medication for a somatic symptom were counted as having no improvement. Commonly documented adverse effects were daytime sedation (5.3%), worsening mental status (2.3%), and nightmares (1%). Conclusions Despite the limitations of this retrospective, qualitative study, these data confirm that mirtazapine is generally well tolerated and can provide at least short-term relief of certain symptoms in medically ill patients. Controlled trials are needed to assess these benefits more systematically, and it is not clear how long mirtazapine should be used for these symptoms.
- Published
- 2016
45. KETAMINE FOR TREATMENT-RESISTANT UNIPOLAR AND BIPOLAR MAJOR DEPRESSION: CRITICAL REVIEW AND IMPLICATIONS FOR CLINICAL PRACTICE
- Author
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Susannah J. Tye, William V. Bobo, Paul E. Croarkin, Jonathan G. Leung, Mark A. Frye, and Jennifer L. Vande Voort
- Subjects
medicine.medical_treatment ,medicine.disease ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,0302 clinical medicine ,Electroconvulsive therapy ,Infusion therapy ,Tolerability ,Anesthesia ,Anesthetic ,medicine ,Major depressive disorder ,Ketamine ,Bipolar disorder ,Psychology ,Treatment-resistant depression ,030217 neurology & neurosurgery ,medicine.drug - Abstract
There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off-label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence-based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.
- Published
- 2016
46. A Single-Dose Crossover Pharmacokinetic Comparison Study of Oral, Rectal and Topical Quetiapine in Healthy Adults
- Author
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Sarah Nelson, Maria I. Lapid, Jonathan G. Leung, William V. Bobo, Julie L. Cunningham, Simon Kung, Ross A. Dierkhising, Matthew F. Plevak, and Virginia H. Thompson
- Subjects
Adult ,Male ,Drug ,medicine.drug_class ,Administration, Topical ,Chemistry, Pharmaceutical ,Drug Compounding ,media_common.quotation_subject ,Administration, Oral ,Biological Availability ,Atypical antipsychotic ,Dosage form ,Quetiapine Fumarate ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Pharmacokinetics ,Administration, Rectal ,medicine ,Humans ,Pharmacology (medical) ,media_common ,Pharmacology ,Cross-Over Studies ,Drug Administration Routes ,030208 emergency & critical care medicine ,Middle Aged ,Crossover study ,Healthy People Programs ,030220 oncology & carcinogenesis ,Anesthesia ,Quetiapine ,Female ,Antipsychotic Agents ,medicine.drug - Abstract
Quetiapine is an oral atypical antipsychotic drug commonly used to treat a large number of neuropsychiatric disorders and conditions. However, a substantial number of patients who may benefit from treatment with quetiapine are unable to ingest quetiapine or other medications by mouth and thus require alternative routes of administration. There are currently no studies evaluating non-oral compounded dosage forms of quetiapine. We conducted a single-dose open-label crossover pharmacokinetic study in 10 healthy adults to determine whether quetiapine compounded as a rectal suppository or a topical cream achieved absorption similar to that achieved by a commercially available oral formulation. Rectal quetiapine produced an area under the plasma concentration–time curve from time zero to infinity (AUC∞) approximately 90 % greater than that produced by an equal (milligram per milligram) dose of oral quetiapine (15,333 ng/mL versus 8118.8 ng/mL, p = 0.005). However, only two of ten subjects who received topical quetiapine had detectable serum levels. When detected, serum levels achieved with topical quetiapine were delayed and low in comparison with those produced by the oral and rectal dosage forms. Our results suggest that rectal, but not topical, quetiapine may be useful in clinical settings. Clinical outcome studies of rectal quetiapine are needed.
- Published
- 2016
47. Vasopressor-Refractory Shock From Clozapine Overdose Treated With Synthetic Angiotensin II Infusion
- Author
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Patrick M. Wieruszewski, Sarah Nelson, Erica D. Wittwer, and Jonathan G. Leung
- Subjects
hypotension ,business.industry ,medicine.drug_class ,resuscitation ,Atypical antipsychotic ,Case Report ,vasopressor ,General Medicine ,angiotensin ,vasodilatory shock ,Refractory hypotension ,Angiotensin II ,Norepinephrine (medication) ,Shock (circulatory) ,Anesthesia ,Renin–angiotensin system ,medicine ,Catecholamine ,overdose ,medicine.symptom ,business ,Clozapine ,medicine.drug - Abstract
Background Clozapine is an atypical antipsychotic with potent alpha-adrenergic blocking properties when administered at high dosages, resulting in vasodilatory shock in overdose settings. Case summary A 39-year-old man presented with profound catecholamine- and vasopressin-refractory vasodilatory shock following massive clozapine ingestion. Angiotensin II was initiated when the patient was requiring 2.2 µg/kg/min norepinephrine equivalents of vasopressor support, resulting in a prompt increase in the perfusion pressure. All vasopressors were liberated within 18 hours of angiotensin II initiation, and the patient was discharged with no deficits. Conclusions Synthetic angiotensin II may represent a therapeutic option for refractory hypotension resulting from high dosages of clozapine or other potent alpha-adrenergic blocking medications.
- Published
- 2020
48. A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization
- Author
-
Jessica L. Gören, Victoria Letts, Ian R. McGrane, Kathryn M. Schak, Dawn Hoeft, Megan Maroney, Betsy Walters Burkey, Jonathan G. Leung, Laura M Steinauer, Sandra Mullen, and Jennifer L. Vande Voort
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Bipolar Disorder ,Neutropenia ,Adolescent ,Psychiatric Department, Hospital ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Pharmacology (medical) ,Bipolar disorder ,Child ,Clozapine ,Retrospective Studies ,business.industry ,Early onset schizophrenia ,Australia ,Sialorrhea ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Psychotic Disorders ,Schizophrenia ,Pediatrics, Perinatology and Child Health ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug ,Antipsychotic Agents - Abstract
Clozapine is the drug of choice for treatment-resistant schizophrenia. While pediatric clozapine use is not contraindicated, the literature describing its clinical application is limited. The primary objective of this study was to assess the use of clozapine in a child and adolescent population by characterizing the documented safety and clinical benefits of the medication.A multicenter retrospective study at sites in the United States and Australia included children and adolescents admitted to a psychiatric unit who were administered at least one dose of clozapine. Information related to demographics, patient history, past treatments, clozapine, and adverse events was collected.Eighty-two patients from eight sites were included in this study. Patients were predominantly clozapine naive (76.8%), and most had a discharge diagnosis of a primary psychotic disorder (61%) or bipolar disorder (25.6%). Four clozapine discontinuations occurred during hospitalization due to severe neutropenia, ileus, need for diagnostic clarification, and significant psychomotor retardation. The remainder (n = 78) were discharged on a mean clozapine dose of 218.1 ± 142.2 mg. Sedation (26.8%) and sialorrhea (17.1%) were the most common documented adverse events. The mean number of previously trialed antipsychotics before clozapine was 3.5 ± 1.4 (range 1-10). Improvement with clozapine was documented as significant (31.7%), moderate (32.9%), minimal (12.2%), no improvement (2.4%), and not described (20.7%).In this cohort, 95% of pediatric patients admitted with or started on clozapine during an acute psychiatric hospitalization were discharged on the medication. The high incidence of adverse events should reinforce to clinicians the need for vigilant monitoring. Pediatric guidelines recommend clozapine for refractory schizophrenia but stress the critical need to ensure an accurate diagnosis. Limited data exist for the use of clozapine in pediatric patients with other diagnoses.
- Published
- 2018
49. Ketamine Use in the Intensive Care Unit
- Author
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Jonathan G. Leung, Patrick M. Wieruszewski, and Sarah Nelson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Critical Care ,MEDLINE ,Pain ,Critical Care Nursing ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Education, Nursing, Continuing ,030202 anesthesiology ,law ,medicine ,Humans ,Pain Management ,Ketamine ,Curriculum ,Analgesics ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,Middle Aged ,Intensive care unit ,United States ,Emergency medicine ,Emergency Medicine ,Female ,business ,medicine.drug - Published
- 2018
50. The Role of Gabapentin in the Management of Alcohol Withdrawal and Dependence
- Author
-
Kristen A. Schmidt, Kathryn M. Schak, Jonathan G. Leung, Sarah Nelson, and Daniel K. Hall-Flavin
- Subjects
Cyclohexanecarboxylic Acids ,Gabapentin ,MEDLINE ,Alcohol ,chemistry.chemical_compound ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Amines ,Prospective cohort study ,gamma-Aminobutyric Acid ,Ethanol ,business.industry ,Alcohol dependence ,Disease Management ,medicine.disease ,Substance Withdrawal Syndrome ,Alcoholism ,Mood ,chemistry ,Anesthesia ,Alcohol withdrawal syndrome ,Anxiety ,medicine.symptom ,business ,medicine.drug - Abstract
Objective: To review the literature evaluating gabapentin for alcohol withdrawal and dependence. Data Sources: A literature search of MEDLINE (1966 to end of March 2015) and PubMed was performed using the terms alcohol, gabapentin, withdrawal, and dependence. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: English-language prospective studies evaluating gabapentin for alcohol withdrawal and dependence were evaluated. Data Synthesis: A total of 10 publications utilizing gabapentin in alcohol withdrawal (n = 5) and alcohol dependence (n = 5) were included in this review. Limited data suggest that gabapentin can provide benefit in managing mild alcohol withdrawal syndrome. There were 5 reported or suspected seizures in the withdrawal studies, suggesting that additional safety data are necessary before gabapentin monotherapy can be routinely considered. Sleep and mood/anxiety-related outcomes were positively influenced by gabapentin, which may result in long-term benefits if continued beyond the withdrawal period for the treatment of alcohol dependence. Studies evaluating gabapentin for alcohol dependence demonstrated dose-dependent benefits for complete abstinence, rates of no heavy drinking, and cravings. Gabapentin used to treat alcohol dependence was well tolerated with no severe adverse reactions reported in the extant literature. Conclusion: Gabapentin may have a role in the treatment of mild alcohol withdrawal, but future studies should focus on adequate dosing strategies. Gabapentin should be considered for the treatment of alcohol dependence when barriers prevent the use of traditional agents. Additional studies should be conducted to further validate findings from the research conducted to date, but the current literature is promising for gabapentin in the treatment of alcohol dependence.
- Published
- 2015
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