Olanzapine-Induced Elevated Liver Function Tests in an Older Person Treated for Antidepressant-Induced Mania.

Patient History A 67-year-old male presented with symptoms of mania eight days after switching from sertraline to bupropion. His past medical history included benign prostatic hyperplasia, erectile dysfunction, insomnia, and a recent diagnosis of depression. He denied previous history of depression but reported taking sertraline for premature ejaculation, an off-label use. His baseline aspartate aminotransferase (AST) was 20 U/L and alanine transaminase (ALT) was 22 U/L. Bupropion was held on admission and olanzapine 5 mg nightly was initiated to treat mania. Following six days of olanzapine treatment, his liver function tests (LFTs) were elevated (AST = 83 U/L, ALT = 105 U/L) and peaked two days later at AST being 2,024 U/L and ALT being 1,508 U/L. Other causes of LFT elevation were ruled out since no other new medications were started and the patient denied use of acetaminophen. Olanzapine was subsequently discontinued and his LFTs began to improve. His symptoms of mania resolved, and he was discharged on no psychotropic medications. Review of Literature A literature search identified 6 cases of bupropion-induced mania/hypomania and 10 cases of olanzapine-induced increased LFTs. This case will add to the limited reports regarding these adverse effects. Conclusion Possible adverse drug reactions (ADRs) were observed between the initiation of bupropion and the development of manic symptoms as well as the initiation of olanzapine and elevated LFTs. The case report also focuses on the role of pharmacy in a patient with multiple ADRs from psychotropic medications and the importance of gaining collateral information and clarifying indications of prescribed medications.

The impact of pharmacy candidates' understanding of psychiatry on personal mental health concerns and patient treatment.

INTRODUCTION: Psychiatry modules in pharmacy education have the potential to address mental health stigma and may help future pharmacists discuss mental health concerns by altering willingness to engage persons with mental illness to better help this patient population. This research aimed to compare the effectiveness of a psychiatry module on pharmacy candidates' own utilization of mental health resources for themselves, as patients, and the ability to address mental illness during patient interactions. METHODS: Forty-six participants completed a 22-item, anonymous questionnaire. Pre- and posttest data were collected to assess perceived impact on patient treatment and self-reflection from their own mental health and treatment. The survey also assessed doctor of pharmacy candidates' changes in comfort level of treating patients with mental illness, referring family or friends for mental health counseling, and personal willingness to obtain counseling with regards to mental health. RESULTS: There were significant differences in pre- and posttest mean scores in participants' comfort level counseling patients with mental illness, comfort level in discussing mental health concerns with patients, and personal willingness to speak with a provider regarding personal mental health. A significant reduction was seen in candidates who personally sought counseling. There was no significant difference in inquiring about personal assistance with mental health concerns or involvement in extracurricular activities within pharmacy school. CONCLUSIONS: A psychiatry module in pharmacy education may positively impact mental health stigma and the ability of pharmacy candidates to openly discuss mental illness as well as improve medication counseling skills for patients needing psychotropic medications.

Evaluation of patient satisfaction and perceptions of a long-acting injectable antipsychotic medication administration service in a community-based pharmacy during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, restrictions, and social distancing requirements for medical offices reduced scheduling availability and increased virtual televisits by providers. COVID-19 restrictions created a barrier to health care access for patients who are being administered long-acting injectable antipsychotics (LAIs) in an already vulnerable population. OBJECTIVE: To describe an LAI medication administration service at a community-based pharmacy during the COVID-19 pandemic, to evaluate patient satisfaction with the administration of LAIs by a pharmacist service in a community-based pharmacy during the COVID-19 pandemic, and to compare the patient's perceptions of receiving LAIs in a community-based pharmacy with those in another setting previously used for medication administration. PRACTICE DESCRIPTION: Independent full-service community-based pharmacy. PRACTICE INNOVATION: Implementation of an LAI administration service after an increase in provider referrals of patients to the community-based pharmacy during the COVID-19 pandemic. EVALUATION METHODS: A 4-month prospective convenience sample study conducted to evaluate the LAI medication administration service. The survey containing 32 questions was adapted with permission from a previous survey administered in a large grocery store chain to a similar population. Survey results were reported using descriptive statistics. RESULTS: Eleven patients completed the survey. A total of 82% of patients strongly agreed that they felt comfortable with receiving this service at the community-based pharmacy and were satisfied with the privacy during the service. Seventy-one percent of patients who received this service elsewhere strongly agreed the LAI medication administration service was more convenient than a similar service received elsewhere, yet only 18% of patients strongly agreed that the community-based pharmacy was near their work or home. CONCLUSION: A medication administration service for LAIs was developed in a community-based pharmacy, and patients were satisfied with the service. Further research needs to be completed to evaluate health outcomes and financial implications of this service for the patient and health care system.

Skin Necrosis Following Inadvertent Dermal Injection of Extended-release Buprenorphine.

INTRODUCTION: Extended-release subcutaneous buprenorphine injection is a relatively new formulation and clinicians are still gaining experience with its use. There is sparse literature available on adverse events. We describe a case of skin necrosis associated with the injection site of extended-release buprenorphine. CASE REPORT: A 35-year-old reported immediate swelling and eventual skin breakdown near his buprenorphine injection site. He was found to have ulceration down to the subcutis with no evidence of infection. The patient followed up with dermatology and underwent debridement of the site. The injection site healed with scar formation. DISCUSSION: Although mild to moderate adverse events related to the injection site have been reported in Phase 3 studies of extended-release buprenorphine injection, this is a rare case of skin necrosis requiring surgical intervention and excision of the depot. CONCLUSIONS: This case highlights the potential complication of skin necrosis after inadvertent dermal of extended-release buprenorphine and reviews proper administration techniques.

Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid.

Introduction: Valproic acid (VPA) and its various formulations can be given in conjunction with clozapine for seizure prophylaxis or for augmentation in schizophrenia. There is conflicting literature on how VPA affects clozapine metabolism and the incidence of clozapine-related side effects. The purpose of this study is to compare the effects of VPA when given concurrently with clozapine to patients on clozapine monotherapy. Methods: A retrospective medical record review was completed to identify patients admitted to the inpatient psychiatry unit at an academic medical center with an order for clozapine with and without concurrent VPA from August 7, 2010 to August 7, 2020. The primary outcome was the difference in clozapine doses in patients on clozapine as monotherapy versus dual therapy with VPA. Secondary outcomes include the difference in incidence of adverse effects in monotherapy versus dual therapy, as well as clozapine and norclozapine concentrations in both treatment groups. Results: During the study period, 73 patients were included in the monotherapy group and 35 patients were included in the dual therapy group. The average clozapine dose in the dual therapy group was 250 mg (95% CI = 194.7, 305.4) which was significantly higher than the average monotherapy dose of 175.9 mg (95% CI = 134.0, 208.7; P = .016). However, there was no significant difference in the average clozapine concentration between the dual therapy group (392.5 ng/mL; 95% CI = 252.8, 532.2) and monotherapy group (365.9 ng/mL; 95% CI = 260.5, 471.3; P = .756). There were higher rates of tachycardia (45.7% vs 17.8%; P = .002), sedation (51.4% vs 8.2%; P < .001), and constipation (42.8% vs 9.5%; P < .001) in the dual therapy group compared to the monotherapy group, respectively. Discussion: Patients on concurrent clozapine and VPA received higher doses of clozapine and experienced a higher incidence of tachycardia, sedation, and constipation.

Evaluation of intramuscular olanzapine and ziprasidone in the medically ill.

INTRODUCTION: Despite the paucity of studies evaluating short-acting parenteral second-generation antipsychotics in the medically ill, their use in this population has increased. The purpose of this study was to characterize the use of IM olanzapine and ziprasidone in the medically ill at an academic medical center. METHODS: This is a retrospective medical record review of all patients who received IM olanzapine or ziprasidone on nonpsychiatric inpatient units at a large academic medical center from August 1, 2015 to July 31, 2017. The primary endpoint characterized the indication for use. Secondary endpoints included safety, effectiveness, and prescribing patterns. RESULTS: After exclusion criteria, a total of 100 patients were included in this study, predominantly white males with a mean age of 56 years. Seventy-four percent of patients received IM ziprasidone and 26% received IM olanzapine. The most common indications for use were agitation of nonpsychotic origin (40%) and delirium (33%). Patients received IM olanzapine and ziprasidone when their use was contraindicated (26.9% vs 9.5%, respectively). DISCUSSION: Intramuscular second-generation antipsychotics are increasingly being used in the medically ill for delirium and agitation. Our study confirms these were the most common indications for IM second-generation antipsychotic use in this population. Additionally, their use appeared to be well-tolerated, and no patient developed Torsades de Pointes even when combined with other agents that putatively increase QTc. Given the retrospective, single-center, nonrandomized design of this study, the safety and effectiveness of these parenteral second-generation antipsychotics in common causes of acute agitation should continue to be further evaluated.

Esketamine: A Novel Option for Treatment-Resistant Depression.

Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (-4.1; 95% CI = -7.69 to -0.49; P = 0.027 [exploratory]) and flexible-dosed arms (-4.0; 95% CI = -7.31 to -0.64; P = 0.02), though the fixed-dose 84-mg arm (-3.2; 95% CI = -6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (-3.6; 95% CI = -7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine's adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine's role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

Lithium-related medication problems on nonpsychiatric inpatient medical units.

PURPOSE: Results of a study of medication-related problems (MRPs) associated with lithium use on nonpsychiatric inpatient medical units are reported. METHODS: In a single-center, retrospective study, the records of all patients hospitalized over a 21-month period who received lithium or had a documented serum lithium concentration during hospitalization were evaluated. The primary objective was to identify patient-specific factors associated with lithium MRPs on nonpsychiatric inpatient medical units. Secondary objectives included characterization of lithium MRPs. Identified MRP occurrences were further evaluated to determine if an intervention was necessary to resolve the MRP and whether or not an intervention was made. RESULTS: A total of 150 patients were included in the study sample. One or more lithium MRPs were identified in 85% of the patients, with a total of 255 lithium MRPs identified. None of the patient-specific factors analyzed were significantly associated with MRP occurrence. Of the 128 patients in whom a lithium MRP occurred, 92.2% (n = 118) were judged to be appropriate candidates for interventions as defined per the study definitions; among those 118 patients, such interventions were documented for only 40.7% (n = 48). CONCLUSION: Lithium MRPs were found to have occurred frequently on nonpsychiatric inpatient medical units at 1 hospital. Laboratory test- related MRPs and drug-drug interactions were the most commonly identified types of MRPs. Interventions to address MRPs were not made in the majority of patients; however, interventions were more frequently made when psychiatry consultation was involved.

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

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.

Caffeine Sodium Benzoate for Electroconvulsive Therapy Augmentation.

OBJECTIVES: Because of an ongoing manufacturer shortage of injectable caffeine sodium benzoate (CSB), patients at our health system were given CSB compounded in-house to increase seizure response during electroconvulsive therapy (ECT). Therefore, we aimed to evaluate its effectiveness and safety as an ECT augmentation agent. METHODS: Medical records of patients who received compounded CSB at Virginia Commonwealth University Health System were reviewed to identify adults receiving it as part of an index ECT treatment course between June 2012 and December 2016. The primary outcome was change in electroencephalogram seizure duration from pre-caffeine session to initial caffeine session. Data were also collected on demographics, motor seizure duration, maximum heart rate, mean arterial pressure, and concurrent medication use for these sessions and the last caffeine session. RESULTS: Seven-one patients were included in the study, predominantly white females with a mean age of 58.6 years. The most common indication for ECT was major depressive disorder resistant to pharmacotherapy (71.8%), followed by catatonia associated with another mental disorder (19.7%). Electroencephalogram seizure duration increased by 24.1 seconds on average with first CSB use (P < 0.0001), allowing 24 more patients overall to achieve goal of at least 30 seconds (P < 0.0001). No clinically significant changes in maximum heart rate or mean arterial pressure were observed, nor did any patients require an abortive agent for prolonged seizure. Five patients (7%) discontinued CSB prematurely: 4 related to adverse effects and 1 secondary to ineffectiveness. CONCLUSIONS: We confirm results of prior studies of the utility of CSB and add that compounded CSB is effective for ECT augmentation, maintaining effectiveness throughout the index course with minimal safety concerns.

Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP). DATA SOURCES: A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson's disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: All English-language trials evaluating pimavanserin in PDP were included. Data from review articles were included if relevant to clinical practice. One phase II and 3 phase III trials are discussed. DATA SYNTHESIS: Pimavanserin was approved in April 2016 for the treatment of delusions and hallucinations of PDP. One phase II and 2 phase III trials reported no difference for primary outcomes when pimavanserin was compared with placebo. The pivotal phase III ACP-103-020 trial adapted a scale to target more specific symptoms prevalent in PDP and showed that least-squares mean differences of the total PD-adapted Scale for the Assessment of Positive Symptoms score were significantly improved for pimavanserin-treated patients as compared with placebo-treated patients (difference = -3.06; 95% CI [-4.91 to -1.20]; P = 0.0014]). Pimavanserin's adverse effect profile includes urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches. CONCLUSION: Pimavanserin is a novel 5-HT2A inverse agonist that has shown promising results for managing hallucinations and delusions in patients with PDP without worsening motor effects or orthostasis. Yet its high cost and specialty pharmacy access may limit use in clinical practice.

2018 American Society of Consultant Pharmacists Annual Meeting & Exhibition.

Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by The Consultant Pharmacist. Industry support is indicated, where applicable. Presenting author is in italics. The poster abstract presentation is supported by the ASCP Foundation.

Dysphagia with second-generation antipsychotics: A case report and review of the literature.

BACKGROUND: All antipsychotics are associated with extrapyramidal symptoms (EPS). These can present as dysphagia, esophageal dysmotility, or aspiration, all of which may not be recognized as EPS. CASE REPORT: A 62-year-old with schizophrenia, prescribed olanzapine 5 mg daily, presented agitated and endorsed difficulty swallowing. Speech therapy suggested her complaints were related to either reflux or dysmotility. Esophageal manometry showed her lower esophageal sphincter was not fully relaxing, and identified an esophagogastric junction outflow obstruction. Despite therapeutic dilation, oral intake remained poor. Following an increase in olanzapine, she developed EPS, her dysphagia worsened, and she was choking on food. Following a switch to aripiprazole her EPS and appetite improved, and she ceased complaining of dysphagia. DISCUSSION: Dysphagia has been reported with first- and second-generation antipsychotics. A review of the second-generation antipsychotic literature identified case reports of dysphagia with clozapine (n = 5), risperidone (n = 5), olanzapine (n = 2), quetiapine (n = 2), aripiprazole (n = 1), and paliperidone (n = 1). Postulated mechanisms of antipsychotic-induced dysphagia include that it may be an extrapyramidal adverse reaction or related to anticholinergic effects of antipsychotics. Management of dysphagia includes discontinuing the antipsychotic, reducing the dose, dividing the dose, or switching to another antipsychotic. Complications of dysphagia include airway obstruction (eg, choking, asphyxia), aspiration pneumonia, and weight loss. Additional complications include dehydration, malnutrition, and nonadherence to oral medications. CONCLUSION: It is important to recognize symptoms of dysphagia and esophageal dysmotility in antipsychotic-treated patients. Intervention is necessary to prevent complications.

Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports.

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling. We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an 'outlier' manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

Methadone, QTc interval prolongation and torsade de pointes: Case reports offer the best understanding of this problem.

We reviewed the literature and found 31 adult cases and 1 newborn case of methadone-associated QTc interval prolongation and/or torsade de pointes (TdP). Parametric statistics may not be useful in studying this issue because methadone-associated TdP is a very rare event and, hence, "an extreme outlier" consistent with scalable randomness. We may have to rely upon narrative medicine in the form of case reports with all its limitations and hazards to provide our best understanding. We report risk factors for methadone-associated QTc interval prolongation and TdP based on review of published case reports. We believe both drug manufacturers and the FDA would better serve our patients and inform clinicians if they more readily reported drug-induced outliers such as methadone-associated TdP using a case report format.

Tamoxifen and depression: drug interactions in breast cancer.

This case describes a 76-year-old African-American female with a history of depression, breast cancer, and hypothyroidism admitted to the inpatient geriatric psychiatry unit for an electroconvulsive therapy (ECT) evaluation. She had one previous episode of depression, which began after a lumpectomy in 2007. Her home medication regimen included tamoxifen 20 mg daily. This case highlights the incidence of depression in persons with breast cancer, examines the controversy of tamoxifen-induced depression, and evaluates antidepressant considerations regarding potentially efficacy-reducing cytochrome P450 2D6 drug interactions with tamoxifen. The pharmacy team played an active role in educating the medical team regarding tamoxifen drug interactions. After many discussions, the patient was ultimately treated with mirtazapine 15 mg at bedtime, in addition to ECT.