Med rec double check: Inpatient psychiatry medication errors identified on admission using Medicaid Web portals and electronic pharmaceutical claims data.

Introduction: The role of pharmacists during medication reconciliation (MR) is well established, with a number of reports describing this in the context of psychiatric hospitalizations. However, medication errors (MEs) are common during transitions of care, with no exception during psychiatric hospitalizations. Our institution uses pharmacy-performed MR processes using patient interviews and reviewing objective sources, such as electronic pharmaceutical claims data (EPCD), which includes Medicaid Web portals. The inpatient psychiatric pharmacist reviews EPCD sources against previously pharmacy-completed MRs for new admissions, where if discrepancies are found, the patient is reinterviewed to identify and correct MEs. Methods: We performed a prospective quality improvement project during 28 days to evaluate the quantity and classification of MEs upon admission to a 22-bed inpatient psychiatry unit. Results: Of 52 included patients, where a cumulative 426 medications were reviewed, a total of 29 MEs in 16 patients were identified. Eight patients had discrepancies on their home medication lists when compared to EPCD, where 7 of these had at least 1 ME due to inaccurate MR. Discussion: Of all the MEs identified, the greatest quantity was found secondary to the EPCD "double-check" method. The most common MEs in all patients were the omission of home medications (34%), wrong frequency (28%), and ordering medication the patient is not taking (10%). All patients admitted on long-acting injection antipsychotics had errors in last dose received. No MEs resulted in patient harm, and they were identified and corrected by the psychiatric pharmacist 97% of the time.

Guidance on using Medicaid web portals and other electronic prescriptions claims data to improve admission medication reconciliation in critical access hospitals.

In an effort to expedite the publication of articles, AJHP is posting 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.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Effects of 3,4-methylenedioxymethamphetamine and methamphetamine on motor vehicle driving performance: A systematic review of experimental and observational studies.

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) are common drugs of abuse and driving under their influence may occur in 1 million people yearly in the United States. This systematic review fills the currently unmet need in understanding the effects of METH and MDMA on motor vehicle driving performance (MVP) and provides insight into the forensic community. A PubMed search on September 24, 2020, for experimental and observational studies, which evaluated the impact of METH and MDMA on MVP was performed. After a review of 208 abstracts, 103 were considered potentially interesting and full texts were obtained. After the exclusion of non-English articles, review articles, single case reports, and articles which did not evaluate METH or MDMA on MVP, a total of nine experimental studies, 10 traditional observational studies, and 35 case series were included. The clinical rigor of experimental studies was evaluated using the Jadad scale. Experimental studies often demonstrated no significant MVP safety signals for METH or MDMA use, which was contrary to the overwhelming MVP safety risks found in observational studies. Common driving behaviors while using METH or MDMA include: errors in judgment, traveling at high speeds, failure to stop, merging inappropriately, lane weaving, and crashes. Limitations of experimental studies that led to dissimilar MVP outcomes from observational studies include: the common use of driving simulators, as opposed to actual driving examinations, and doses of METH or MDMA administered may not be representative of blood concentrations seen in observational studies. This systematic review has no funding source and was not registered.

Pharmacokinetic drug interactions with oral haloperidol in adults: dose correction factors from a combined weighted analysis.

INTRODUCTION: Pharmacokinetic (PK) drug-drug interactions (DDIs) of oral haloperidol, a first-generation antipsychotic, are systematically reviewed. AREAS COVERED: After exclusions, the search for DDIs with oral haloperidol provided 47 articles as victim and 7 as perpetrator. Changes in mean haloperidol concentration-to-dose (C/D) ratios after weighting each study's size were used to calculate the effects of other drugs (inhibitors/inducers) on haloperidol. These changes of haloperidol C/D ratio were used to estimate dose-correction factors (<1 for inhibitors and >1 for inducers). EXPERT OPINION: A box summarizes our recommendations for clinicians regarding our current knowledge of haloperidol PK DDIs, which will need to be updated as new information becomes available. Moderate to strong inducers (carbamazepine, phenobarbital, phenytoin, or rifampin) should be avoided since they required dose-correction factors of 2-5. Smoking appeared to be a weak inducer (dose-correction factor 1.2). Fluvoxamine, promethazine, and combinations of CYP3A4 and CYP2D6 inhibitors should be avoided. There are no long-term studies on fluoxetine to provide a dose correction factor. Limited information suggests that valproate may be an inhibitor (dose-correction factor 0.6). In most patients, haloperidol may not have clinically relevant effects as a perpetrator, but in vitro and clinical studies suggest it is a weak CYP2D6 inhibitor.

Lithium therapy in patients on dialysis: A systematic review.

BACKGROUND: Lithium is a first-line pharmacotherapy for the treatment of bipolar disorder, but long-term use is associated with nephrotoxicity. However, as dialysis effectively eliminates lithium, it remains a pharmacotherapeutic option for patients on dialysis. This systematic review seeks to evaluate the dosing, safety, efficacy, and monitoring of lithium in patients receiving dialysis. METHOD: A PubMed database search performed May 5th, 2020, identified 535 article titles. After exclusion criteria were applied, a total of 15 articles were included in this systematic review. RESULTS: In 18 patients receiving dialysis, lithium was primarily used for the treatment of mood disorders. The majority of patients received 300-900 mg lithium carbonate thrice-weekly following dialysis, but several alternative lithium salts and dosing strategies were utilized. The pharmacokinetic properties of lithium in dialysis are not well understood and can be complicated by a serum lithium "rebound effect" following dialysis, due to a two-compartment volume of distribution. Additionally, presence of residual diuresis in some patients may be reason to administer lithium more frequently than thrice-weekly following dialysis. Lithium was shown to be an effective pharmacotherapy in all patients, with many demonstrating rapid improvement after drug initiation. Five patients experienced an adverse event on lithium, but only one patient required lithium discontinuation. CONCLUSION: Lithium may be used in patients on dialysis, with close monitoring of pre-dialysis serum lithium concentrations for at least two weeks after treatment initiation, followed by a lower frequency after stabilization to ensure therapeutic concentrations and reduce toxicity risk.

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

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.

Possible inhibitory effects of terbinafine on aripiprazole metabolism: Two case reports.

Aripiprazole, an atypical antipsychotic, is a metabolic substrate for cytochrome P450 (CYP)3A4 and 2D6. Terbinafine, an antifungal agent used for onychomycosis, is a CYP2D6 inhibitor and could theoretically reduce the metabolism of aripiprazole. However, there are no published reports describing this interaction. We present 2 female patients hospitalized in a psychiatric unit who were both taking aripiprazole 15 mg daily and terbinafine 250 mg daily prior to admission. The first patient was a 58-year-old female who was prescribed aripiprazole and terbinafine concomitantly for approximately 5 months prior to admission. A commercial pharmacogenetic testing platform classified this patient as a normal metabolizer for CYP3A4 and 2D6. The first patient's serum trough aripiprazole concentration at steady-state concentration (Css) was 207.5 ng/mL. The second patient was a 43-year-old female who was taking aripiprazole and terbinafine concomitantly for approximately 2 weeks prior to admission who had a Css aripiprazole concentration of 278.9 ng/mL. Aripiprazole has a wide therapeutic range (100 to 350 ng/mL) and a reference dose-related drug concentration of 11.7 (mean) ± 5.6 (SD) ng/mL/mg/d. Our patients had Css aripiprazole concentrations 18% and 59% higher than guideline-supported dose-related drug concentrations. Through the use of therapeutic drug monitoring, pharmacogenetic data, electronic pharmaceutical claims data, and the Drug Interaction Probability Scale, we suggest terbinafine possibly increases aripiprazole concentrations 18% to 59%. Further reports are needed to confirm these findings prior to using this information in clinical practice.

A prospective assessment of the Medicaid Web portal for admission medication reconciliation at a community hospital in Montana.

PURPOSE: Medication reconciliation (MR) is a complicated and tedious process but is crucial to prevent errors when ordering patients' discharge medications during a hospital admission. Our institution currently uses a variety of methods to gather a patient's medication history, including review of the medical records and electronic pharmaceutical claims data (EPCD) from a commercial health information exchange organization, as well as a patient or caregiver interview. Occasionally, more information is needed to obtain the most accurate history. To augment current methods, EPCD can also be accessed for patients with Medicaid insurance using a state Medicaid Web portal. We aimed to evaluate the utility of the Medicaid Web portal for reducing medication errors during the MR process at hospital admission. SUMMARY: A single-center, prospective, quality improvement initiative was conducted to evaluate 100 patient medication lists for all nonobstetric Medicaid patients admitted to our institution to identify discrepancies in medication lists when the state Medicaid Web portal was used in addition to standard MR methods. We found that, when EPCD from commercial organizations were available, they matched the patient's current medication list 64% of the time. One in 4 patients had at least 1 discrepancy on their verified medication list that was identified using the Medicaid Web portal. The discrepancies identified were addressed and corrected in real time to improve patient care. CONCLUSION: EPCD from the state Medicaid Web portal could supplement the use of current methods to obtain a more accurate medication history and reduce the number of erroneously ordered discharge medications during hospital admission.

Treatment Approach and Modalities for Management of Depression in Older People.

Depression is common in older people, and while the approach to treatment is similar to a younger population, there are several additional treatment considerations to make based on comorbidities and cognitive impairment. Evidence-based psychotherapies such as cognitive behavioral therapy, interpersonal psychotherapy, and problem-solving therapy are recommended for mild-moderate depression in older people; however, the efficacy of these are limited in very old patients (older than 75 years of age) and those with cognitive impairment. Additionally, neuromodulation treatments such as electroconvulsive therapy and transcranial magnetic stimulation could prove beneficial for specific older people with depression. Use of pharmacotherapy that has demonstrated to be safe in older adults, as well as agents with adequate clinical experience in this population, should be considered based on patient-specific characteristics. Because of generally more complex medication regimens, risks of pharmacotherapy should be minimized with careful dosing strategies and special attention to avoid significant drug-drug interactions. While some data are available, antidepressant combination or augmentation strategies are less well studied in older people who fail to achieve remission or those with treatment-resistant depression, compared with younger populations.

Successful bilateral electroconvulsive therapy in a patient with a seizure disorder taking levetiracetam, lorazepam, and zonisamide: A case report.

Electroconvulsive therapy (ECT) may be considered for treatment of severe, treatment-resistant, and emergent depression associated with MDD or bipolar disorder. Patients with epilepsy usually take medications that raise the seizure threshold, which poses challenges during ECT. We report a 66-year-old male with epilepsy taking levetiracetam extended-release (XR), lorazepam, and zonisamide requiring ECT for severe MDD. After literature review, the XR form of levetiracetam was changed to higher doses of the immediate-release (IR) formulation, and zonisamide was discontinued 2 days prior to ECT in the hospital and was resumed when the patient underwent outpatient continuation ECT. The patient was treated to remission after receiving 8 acute bilateral ECT treatments before being transitioned to continuation ECT. We provide a brief review of medication management of antiepileptic drugs and other medications that increase the seizure threshold during ECT. To our knowledge, this is the first reported case describing the management of levetiracetam, lorazepam, and zonisamide concomitantly during ECT. Our case suggests that utilizing the IR formulation of levetiracetam, administering the evening dose early the day prior to the procedure, and temporarily discontinuing zonisamide prior to bilateral ECT is effective for the treatment of severe MDD while maintaining seizure prophylaxis.

Roux-en-Y Gastric Bypass and Antipsychotic Therapeutic Drug Monitoring: Two Cases.

Many patients with psychiatric conditions undergo bariatric surgery. The Roux-en-Y gastric bypass (RYGB) procedure alters medication pharmacokinetic properties and may have significant impact on drug response. Our report is the first to describe atypical antipsychotic therapeutic drug monitoring in patients who have undergone RYGB. The first patient is a 53-year-old female with a stable psychiatric condition undergoing a laparoscopic RYGB. Her medications prior and following the procedure include bupropion, fluvoxamine, lurasidone, methylphenidate, oxcarbazepine, and verapamil. A concentration steady-state lurasidone concentration obtained prior to the procedure was 20 ng/mL and returned at 8.1 ng/mL, 29 days after surgery. The second patient is a 42-year-old female psychiatric inpatient who had previously undergone an RYGB procedure. Medications on admission included phenytoin, oxcarbazepine, risperidone, and venlafaxine. The patient was believed to be a good candidate for a long-acting antipsychotic and paliperidone was chosen. After concentration-steady-state on 6 mg oral paliperidone, a 23.5-hour trough level was drawn. The patient was noted to be improved on the oral paliperidone, the paliperidone long-acting injection was given, and the patient was discharged. After discharge, the paliperidone concentration returned very low at 1.1 ng/mL. We describe the contributions of drug-drug interactions, medication release mechanisms, and food coadministration that may have affected our therapeutic drug monitoring. Our therapeutic drug monitoring results need to be replicated prior to use in the general population but suggest that oral extended-release drug formulations are particularly poor choices and that nonoral antipsychotic formulations may be preferred in some patients who have undergone RYBG.

Probable Genitourinary Adverse Events Associated With Atomoxetine in an Adult Male: A Case Report.

Atomoxetine is a norepinephrine reuptake inhibitor used for treatment of attention-deficit/hyperactivity disorder. Prescribing information from the manufacturer lists genitourinary-related adverse events such as urinary hesitancy/retention and priapism as precautions for atomoxetine. We report a case of urinary hesitancy with milky, white-colored discharge associated with atomoxetine use in a 42-year-old male. The onset of genitourinary symptoms occurred within 2 days of atomoxetine 40 mg daily initiation. Laboratories, urinalysis, sexually transmitted infection analysis, and genital examinations were all unremarkable. Within 2 days of atomoxetine discontinuation, the genitourinary symptoms were no longer present. We calculated a Naranjo adverse event score of 5, indicating atomoxetine probably caused the genitourinary adverse events. A review of literature suggests that urine outflow obstruction-related adverse events occur more commonly in men compared to women. Discontinuation of atomoxetine appears to lead to rapid resolution of the adverse events. Additionally, spontaneous ejaculation and sexual side effects rarely occur with atomoxetine. Clinicians should educate and monitor patients explicitly for genitourinary-related adverse events, as they may not be spontaneously reported.

Possible Garcinia cambogia-Induced Mania With Psychosis: A Case Report.

Garcinia cambogia is a Southeast Asian fruit becoming increasingly popular as a weight management supplement. Hydroxycitric acid (HCA) is the primary active ingredient which demonstrates serotonergic- and muscarinic-enhancing properties via inhibition of selective serotonin reuptake and acetylcholinesterase. We report a young adult female with no history of bipolar disorder who developed mania and psychosis approximately 1 week following initiation of G cambogia and the Cleanse and Detox™ dietary supplement manufactured by Apex Vitality Health. She presented with a predominantly expansive mood, psychomotor agitation, disorganized and pressured speech, flight of ideas, grandiosity, delusions, and auditory hallucinations. Following discontinuation of G cambogia and the initiation of lithium and quetiapine, the patient experienced rapid and progressive mood stabilization and was discharged after 8 days. Seven previous case reports associating (hypo)mania and/or psychosis with G cambogia consumption have been published. The chronology of mania and/or psychosis onset may appear between 1 and 8 weeks following initiation of G cambogia. Psychiatric symptoms have resolved with G cambogia discontinuation in some instances and may not require chronic pharmacotherapy. Our report should encourage further research and case reports regarding this adverse event and the reconciliation of complete herbal supplement use at clinic visits and hospital admissions.

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

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.