Publications by authors named "Jonathan G Leung"

54 Publications

Assessment of gender differences in letters of recommendation for pharmacy residency applicants.

Am J Health Syst Pharm 2021 Apr 4. Epub 2021 Apr 4.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

Disclaimer: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

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 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 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.
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http://dx.doi.org/10.1093/ajhp/zxab150DOI Listing
April 2021

Pharmacologic Management of Status Epilepticus.

AACN Adv Crit Care 2020 Dec;31(4):349-356

Patrick M. Wieruszewski is Clinical Pharmacy Specialist, Cardiothoracic Surgery and Anesthesia Critical Care, Mayo Clinic, Department of Pharmacy, Rochester, Minnesota.

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http://dx.doi.org/10.4037/aacnacc2020907DOI Listing
December 2020

Successful Continuation of Clozapine in Conjunction With Chimeric Antigen Receptor T-Cell (CAR-T) Immunotherapy: Case Report.

Clin Lymphoma Myeloma Leuk 2021 Feb 22;21(2):e194-e197. Epub 2020 Oct 22.

Division of Hematology, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.clml.2020.10.010DOI Listing
February 2021

Retrospective Analysis of Gabapentin for Alcohol Withdrawal in the Hospital Setting: The Mayo Clinic Experience.

Mayo Clin Proc Innov Qual Outcomes 2020 Oct 19;4(5):542-549. Epub 2020 Aug 19.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

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 (=.012). Maximum CIWA score was 2.2 points lower in the gabapentin group (=.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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http://dx.doi.org/10.1016/j.mayocpiqo.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560568PMC
October 2020

Vasopressor-Refractory Shock From Clozapine Overdose Treated With Synthetic Angiotensin II Infusion.

Crit Care Explor 2020 Sep 14;2(9):e0185. Epub 2020 Sep 14.

Department of Pharmacy, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1097/CCE.0000000000000185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491889PMC
September 2020

Second-Generation Antipsychotics and Pneumonia-Related Hospitalizations.

Prim Care Companion CNS Disord 2020 Aug 6;22(4). Epub 2020 Aug 6.

1216 2nd St SW, Rochester, MN 55902.

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.
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http://dx.doi.org/10.4088/PCC.20m02594DOI Listing
August 2020

Pharmacogenetic testing in psychiatric inpatients with polypharmacy is associated with decreased medication side effects but not via medication changes.

J Psychiatr Res 2020 07 10;126:105-111. Epub 2020 May 10.

Mayo Clinic Department of Pharmacy. 1216 2nd St SW, Rochester, MN, 55902, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpsychires.2020.05.002DOI Listing
July 2020

Clozapine treated patients and COVID-19: Ensuring continued care through collaboration.

Schizophr Res 2020 08 14;222:507-508. Epub 2020 May 14.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, Mayo Clinic - Rochester, 1216 Second Street SW, Rochester, MN 55902, United States of America.

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http://dx.doi.org/10.1016/j.schres.2020.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221367PMC
August 2020

Predatory Journals: A Cautionary Tale and a Lesson in Copyright Transfer.

Mayo Clin Proc 2020 03;95(3):441-444

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; Mental Health and Addiction Services, Mercy Hospital, part of Allina Health, Minneapolis, MN.

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http://dx.doi.org/10.1016/j.mayocp.2019.09.001DOI Listing
March 2020

The professional sabbatical: A systematic review and considerations for the health-system pharmacist.

Res Social Adm Pharm 2020 Dec 24;16(12):1632-1644. Epub 2020 Feb 24.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

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.
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http://dx.doi.org/10.1016/j.sapharm.2020.02.011DOI Listing
December 2020

The professional sabbatical: A systematic review and considerations for the health-system pharmacist.

Res Social Adm Pharm 2020 Dec 24;16(12):1632-1644. Epub 2020 Feb 24.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

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.
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http://dx.doi.org/10.1016/j.sapharm.2020.02.011DOI Listing
December 2020

Mirtazapine's effect on the QT interval in medically hospitalized patients.

Ment Health Clin 2020 Jan 9;10(1):30-33. Epub 2020 Jan 9.

Introduction: Mirtazapine is generally well tolerated in medically ill patients with and without formal psychiatric comorbidity to target sleep, appetite, nausea, and pain. However, there is little data regarding mirtazapine's potential to prolong the corrected QT interval (QTc) in this population.

Methods: From a retrospective cohort of patients hospitalized on a variety of medical units for whom a psychiatric consult recommended mirtazapine, electrocardiogram (ECG) data were extracted for ECGs obtained up to 3 days before and 6 days after the initial consult. Descriptive statistics were used to characterize the QTc changes and adverse cardiac outcomes, including incident ventricular tachycardia, torsades de pointes, and sudden cardiac death. Multiple linear regression models were completed to assess the effect of potential confounding variables on QTc changes.

Results: Complete premirtazapine and postmirtazapine ECG data were available for 61 patients, and the average change in QTc was -0.31 ms (SD = 36.62 ms). No incidental adverse cardiac outcomes were found. QTc changes were not significantly affected by patient age and sex, initial and maximum mirtazapine dose, days between ECGs, number of concomitant QTc prolonging medications, Charlson comorbidity scores, and electrolyte abnormalities. Due to incomplete potassium, magnesium, and ionized calcium data, electrolytes were excluded from the final regression model.

Discussion: Despite the limitations of this retrospective study, these data suggest that modest doses of mirtazapine may not significantly affect the QTc in medically ill patients. Retrospective cohorts are more feasibly analyzed, but prospective controlled trials could more systematically assess QTc changes with higher doses of mirtazapine in medical settings.
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http://dx.doi.org/10.9740/mhc.2020.01.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956977PMC
January 2020

Addressing clozapine under-prescribing and barriers to initiation: a psychiatrist, advanced practice provider, and trainee survey.

Int Clin Psychopharmacol 2019 09;34(5):247-256

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.

Clozapine use has declined, despite its superior antipsychotic efficacy in treatment-resistant schizophrenia. Implications for clozapine underutilization include suboptimal treatment outcomes and increased hospitalizations. Many barriers preventing the use of clozapine have been described in the literature, including suboptimal knowledge and poor perceptions. The aim of this study was to assess psychiatry prescribers' perception and knowledge of clozapine. A survey was distributed to advanced practice providers, psychiatrists, and trainees (i.e. residents and fellows) at 10 medical centers within the US and Canada. The survey asked respondents about their perception of clozapine use and assessed their pharmacotherapeutic knowledge of clozapine. Two hundred eleven individual submitted completed surveys of a possible 1152; a response rate of 18.3%. There were no statistically significant differences between the advanced practice provider plus psychiatrist groups and the trainee group for most perception (eight of nine) and knowledge (eight of nine) questions. The knowledge questions with the lowest scores pertained to clozapine reinitiation and myocarditis. The majority of all respondents (144, 68.2%) felt that clozapine prescribing was a burden. Findings of this study support the need for continued clozapine education regardless of a prescriber's age/experience. Future studies to assess barriers to clozapine prescribing should extend beyond academic centers.
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http://dx.doi.org/10.1097/YIC.0000000000000269DOI Listing
September 2019

Prescribing Practices for Patients With Borderline Personality Disorder During Psychiatric Hospitalizations.

J Pers Disord 2020 Dec 11;34(6):736-749. Epub 2019 Feb 11.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota.

This study aimed to understand prescribing practices during acute psychiatric hospitalization in a large cohort of patients ( = 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.
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http://dx.doi.org/10.1521/pedi_2019_33_405DOI Listing
December 2020

Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population.

Pharmacol Res Perspect 2019 02 23;7(1):e00461. Epub 2019 Jan 23.

Department of Psychiatry & Psychology Mayo Clinic Rochester Minnesota.

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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http://dx.doi.org/10.1002/prp2.461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344796PMC
February 2019

A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization.

J Child Adolesc Psychopharmacol 2018 11 24;28(9):615-619. Epub 2018 Oct 24.

10 Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota.

Objectives: 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.

Methods: 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.

Results: 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%).

Conclusions: 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.
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http://dx.doi.org/10.1089/cap.2018.0036DOI Listing
November 2018

Ketamine Use in the Intensive Care Unit.

AACN Adv Crit Care 2018 ;29(2):101-106

Patrick M. Wieruszewski is PGY-2 Critical Care Pharmacy Resident, Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. Jonathan G. Leung is Clinical Pharmacist, Psychiatric Specialist, Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. Sarah Nelson is Clinical Pharmacist, Critical Care Specialist, Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, MN 55905

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http://dx.doi.org/10.4037/aacnacc2018448DOI Listing
January 2019

Use of a Gabapentin Protocol for the Management of Alcohol Withdrawal: A Preliminary Experience Expanding From the Consultation-Liaison Psychiatry Service.

Psychosomatics 2018 Sep - Oct;59(5):496-505. Epub 2018 Mar 21.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1016/j.psym.2018.03.002DOI Listing
May 2019

Clozapine-induced cardiomyopathy and myocarditis monitoring: A systematic review.

Schizophr Res 2018 09 13;199:17-30. Epub 2018 Mar 13.

Pharmacy Services, Mayo Clinic, Rochester, MN, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.schres.2018.03.006DOI Listing
September 2018

A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults.

Am J Hosp Palliat Care 2018 Aug 17;35(8):1076-1080. Epub 2018 Jan 17.

1 Hospital Pharmacy Services, Mayo Clinic Hospital, Rochester, MN, USA.

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.
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http://dx.doi.org/10.1177/1049909117753828DOI Listing
August 2018

Lymphoma following clozapine exposure: More information needed.

Schizophr Res 2018 09 9;199:420-421. Epub 2018 Jan 9.

Division of Hematology, Department of Internal Medicine, Mayo Clinic - Rochester, 200 First Street SW, Rochester, MN 55905, United States.

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http://dx.doi.org/10.1016/j.schres.2017.12.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093049PMC
September 2018

Increasing the Safety of Clozapine Management in Hospitalized Patients With or Without Infection: Still Much to Learn … and Teach.

Authors:
Jonathan G Leung

Psychosomatics 2018 Jan - Feb;59(1):102-104. Epub 2017 Jul 18.

Department of Pharmacy, Mayo Clinic, Rochester, MN. Electronic address:

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http://dx.doi.org/10.1016/j.psym.2017.07.006DOI Listing
November 2018

Concurrent Electroconvulsive Therapy and Bupropion Treatment.

J ECT 2017 Sep;33(3):185-189

From the Departments of *Psychiatry and Psychology and †Hospital Services, and ‡Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1097/YCT.0000000000000423DOI Listing
September 2017

Rectal Bioavailability of Sertraline Tablets in a Critically Ill Patient With Bowel Compromise.

J Clin Psychopharmacol 2017 06;37(3):372-373

Department of Pharmacy, Mayo Clinic, Rochester, MN Department of Psychology and Psychiatry, Mayo Clinic, Rochester, MN Department of Surgery, Mayo Clinic, Rochester, MN Department of Pharmacy, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1097/JCP.0000000000000685DOI Listing
June 2017

Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine.

Psychosomatics 2017 Mar - Apr;58(2):164-172. Epub 2016 Nov 18.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1016/j.psym.2016.11.013DOI Listing
November 2017

Potential problems surrounding the use of sublingually administered ophthalmic atropine for sialorrhea.

Schizophr Res 2017 07 30;185:202-203. Epub 2016 Dec 30.

Department of Psychiatry and Psychology, Mayo Clinic - Rochester, 1216 Second Street SW, Rochester, MN 55902, United States.

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http://dx.doi.org/10.1016/j.schres.2016.12.028DOI Listing
July 2017

Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms.

Case Rep Psychiatry 2016 30;2016:2180748. Epub 2016 May 30.

Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA.

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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http://dx.doi.org/10.1155/2016/2180748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904080PMC
June 2016

Introduction to the CPNP 2016 Poster Abstracts.

Authors:
Jonathan G Leung

J Pharm Pract 2016 06;29(3):269

College of Psychiatric & Neurologic Pharmacists.

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http://dx.doi.org/10.1177/0897190016645331DOI Listing
June 2016

Management of Psychotropic Drug-Induced DRESS Syndrome: A Systematic Review.

Mayo Clin Proc 2016 06 25;91(6):787-801. Epub 2016 Apr 25.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous eruption that has been linked to several common drugs and drug categories, including antiepileptics, allopurinol, sulfonamides, and various antibiotics; however, because of a number of recent case reports linking psychotropic medications to this condition, DRESS is increasingly recognized among psychiatrists. We systematically reviewed all psychotropic drugs linked to DRESS syndrome, and this article summarizes the clinical management relevant to psychiatric professionals. A comprehensive search was performed using Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Litt's Drug Eruption and Reaction Database for articles published in English during the past 20 years (1996-2015) using the search terms (1) psychotropic drugs OR serotonin uptake inhibitors AND DRESS or (2) psychotropic drugs AND drug reaction (or rash) eosinophilia systemic syndrome, and all article abstracts were screened for inclusion and exclusion criteria by 3 reviewers. Two independent reviewers examined the full text of 163 articles, of which 96 (25 original articles, 12 review articles, 55 case reports, and 4 letters to the editor) were included in the systematic review. We identified 1072 cases of psychotropic drug-induced DRESS, with carbamazepine, lamotrigine, phenytoin, valproate, and phenobarbital being the most implicated drugs. Based on our review of the literature, we outline management principles that include prompt withdrawal of the causative drug, hospitalization, corticosteroid therapy, and novel treatments, including intravenous immunoglobulin, cyclophosphamide, and cyclosporine, for corticosteroid-resistant DRESS. Finally, we outline strategies for treating comorbid psychiatric illness after a DRESS reaction to the psychotropic medication.
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http://dx.doi.org/10.1016/j.mayocp.2016.03.006DOI Listing
June 2016

Mirtazapine for Symptomatic Relief on a Psychiatric Consultation Service: A Case Series.

Psychosomatics 2016 Jul-Aug;57(4):409-13. Epub 2016 Mar 2.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1016/j.psym.2016.02.012DOI Listing
August 2017