In October 2015, the Food and Drug Administration (FDA) instituted an update to the mandatory Risk Evaluation and Mitigation Strategy (REMS) program for clozapine to improve safety monitoring of hematologic events. However, the impact of the clozapine REMS program on reporting of hematologic adverse events has not been quantified. We assessed adverse event reports for agranulocytosis, granulocytopenia, leukopenia, and neutropenia from the FDA Adverse Event Reporting System (FAERS) for a 1-year time period before (October 2014 to September 2015, pre-REMS) and after (October 2015 to September 2016, post-REMS) the implementation of the clozapine REMS program. The AERSMine platform was used to capture historical effect estimates (October 2004 to September 2014). Reporting odds ratios (ROR), proportional reporting ratios (PRR), and corresponding Taylor series 95% confidence intervals (CIs) were calculated for hematologic events with clozapine compared with all other medications using OpenEpi. Reporting rates for agranulocytosis, granulocytopenia, leukopenia, and neutropenia with clozapine all increased from the pre-REMS to post-REMS time frames, ranging from a 2-fold increase with leukopenia to a 40-fold increase with neutropenia; the composite measure of all hematologic reports had a 12-fold increase. During the post-REMS time frame, the ROR increased by 1691% (111.4, 95% CI 100.6-123.4) compared with the pre-REMS time frame (7.1, 95% CI 5.2-9.6), and the PRR increased by 1280% (83.1, 95% CI 76.8-90.0 vs 6.9, 95% CI 5.1-9.4) for the composite outcome. We observed significant increases in reports of hematologic adverse events with clozapine after the introduction of the clozapine REMS program. Future research should explore the impact of the less stringent exclusionary and discontinuation criteria on utilization (eg, expanded access) and clinical outcomes (eg, treatment effectiveness and adverse events).Abstract
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Mental health services are an area of high need in many health care systems in the United States. With a limited number of psychiatric providers and a projected increase in the deficit of psychiatrists, a call for increased mental health services is apparent. The inclusion of mental health clinical pharmacy specialists (MH-CPS) as part of interdisciplinary care teams has enabled the William S. Middleton Memorial Veterans Hospital & Clinics as well as numerous other Veterans Affairs sites to improve access to mental health providers when pharmacists serve as an integral part of the mental health team. Our objectives were to (1) evaluate impressions of nonpharmacist mental health providers of MH-CPS and (2) assess for areas of improvement in MH-CPS services. A survey was formulated, using 5-point Likert scale criteria, to evaluate impressions of MH-CPS from other mental health providers. Questions were designed to address impressions of clinical skills, knowledge, team contribution, and comfort with MH-CPS providers. These were distributed and completed in December 2018 by members of mental health treatment teams at the William S. Middleton Memorial Veterans Hospital & Clinics. Overall, mental health team members rated satisfaction with MH-CPS highly across all evaluated criteria. Per review of these results, MH-CPS are a valued and respected part of the mental health team.Abstract
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Opioid use disorder (OUD) can cause significant morbidity and mortality with more than 115 people dying from an opioid overdose daily in the United States. Treatment with buprenorphine/naloxone (BUP/NAL) can be effective; however, there is conflicting evidence on the utility of higher doses in preventing relapse. This study was designed to assess BUP/NAL maintenance doses and the rate of relapse in veterans with OUD. Patients diagnosed with OUD who received a prescription for BUP/NAL through the substance use disorder recovery program were retrospectively evaluated. Patients were categorized into 2 treatment groups: those prescribed ≤16 mg of BUP/NAL daily and those prescribed >16 mg of BUP/NAL daily. The primary outcome was to determine rates of relapse between maintenance doses of BUP/NAL. Secondary outcomes included evaluating the difference in rates of relapse between daily versus take-home dosing, tablets versus films, time to relapse, and use of illicit substances during treatment. Patients prescribed >16 mg of BUP/NAL daily had statistically significantly lower rates of relapse compared to patients prescribed ≤16 mg of BUP/NAL daily (P = .0018). Regarding secondary outcomes, there was a statistically significant difference in time to relapse (P = .036) and dosage form (P = .0124). Difference in administration of dose and illicit substance use during treatment were not statistically significant. This study identified that rate of relapse can be lowered and time to relapse can be lengthened when doses >16 mg of BUP/NAL are prescribed in the veteran population for OUD.Abstract
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Desvenlafaxine is a potent selective serotonin and norepinephrine reuptake inhibitor used to treat depression and anxiety. Several antidepressants have been associated with drug-induced hyperglycemia, but currently there are no reports for desvenlafaxine. A case of suspected desvenlafaxine-induced hyperglycemia is presented involving a 59-year-old female with type 2 diabetes whose average blood glucose increased by 30 mg/dL for fasting blood glucose and 75 mg/dL for postprandial blood glucose 1 month after switching from venlafaxine to desvenlafaxine. Prior to starting desvenlafaxine, she was stable on metformin 1000 mg twice daily, insulin glargine 8 units daily, and dulaglutide 1.5 mg once weekly. Over the course of 3 months after desvenlafaxine initiation, insulin glargine was increased and insulin lispro was initiated as the patient refused alternative antidepressant therapy due to favorable improvements in anxiety and depression. No other cause for elevated blood glucose could be elucidated. The Naranjo scale resulted in a score of 3, indicating a possible cause for the adverse drug reaction. Antidepressants have been associated with glucose dysregulation. However, literature also demonstrates improved glycemic control in treated versus untreated depression. If altered glucose levels are noted, all potential causative factors should be evaluated and risks and benefits weighed to guide therapy.Abstract
This case demonstrates a false elevation of serum lithium concentrations that can occur when blood samples are collected using lithium heparin (green-top) tubes. The patient was a 58-year-old female on chronic lithium therapy for bipolar disorder who presented to the emergency department following an overdose of 5 unidentified medications. The patient was overly sedated and exhibited paradoxical laughter, slurred speech, and mild abdominal pain. The recommended maintenance lithium concentration is 0.6 to 1.0 mmol/L, and she had previously been stable within this therapeutic range. The initial lithium concentration drawn upon admission was 2.05 mmol/L. No intervening treatment was made with the exception of intravenous fluids due to a lack of correlation between clinical presentation and the lithium concentration. Six hours later, a repeat lithium concentration of <0.10 mmol/L was obtained. Upon investigation, it was discovered that the initial blood sample was obtained in a lithium heparin green-top tube instead of the recommended plastic tubes with either sodium heparin or dipotassium ethylenediamine tetraacetic acid as the anticoagulant. As this case demonstrates, lithium heparin tubes have the potential to cause falsely elevated lithium concentrations. It is important for health care professionals to be aware of the false elevations that can occur when blood samples are taken in this type of tube.Abstract
Stiff-person syndrome (SPS) is a neurologic disorder characterized by muscle stiffness, rigidity, and muscle spasms, and it can increase a patient's risk for falls. It is recognized as a rare disease with limited clinical guidelines to manage the condition and its symptoms. Currently, there is even less clinical guidance for the management of common comorbid conditions in these patients. This patient case report aims to evaluate the efficacy of various medications for symptom management in a patient with SPS and comorbid psychiatric disorders, specifically bipolar I and panic disorder. Throughout the patient's course of treatment, various medications were trialed, including fluoxetine, hydroxyzine, valproic acid, propranolol, and clonazepam. Ultimately, fluoxetine, hydroxyzine, and propranolol were discontinued due to adverse drug reactions and incomplete symptom resolution. The patient's bipolar I disorder was adequately managed with valproic acid. Once the clonazepam was changed from as-needed to scheduled dosing, the patient's panic disorder and anxiety-triggered spasms were well controlled. The efficacy of benzodiazepines, specifically high doses of diazepam, in alleviating muscle spasms and anxiety in SPS has been demonstrated in the literature. Case reports including patients with SPS that are prescribed selective serotonin reuptake inhibitors provide controversial evidence as some studies report exacerbation of SPS symptoms with prolonged use. As this case report and literature review suggest, patients with SPS and comorbid panic disorder and anxiety-triggered spasms may benefit from the use of benzodiazepines. The use of other medication classes for the treatment of other comorbid psychiatric disorders in a patient with SPS is lacking evidence.Abstract
In light of the ongoing opioid crisis, many have encouraged the medical community as well as local and national US government agencies to reconsider the prevalent use of benzodiazepines. As prescribers continue to weigh the risks and benefits of ongoing benzodiazepine use, care must be taken when the decision is made to taper and discontinue these medications in patients who have been maintained on them chronically. We present a case of an adult patient maintained on a benzodiazepine for several years who developed tinnitus during a gradual dose taper. This patient developed tinnitus within 7 weeks of gradual reduction of the patient's clonazepam dose to 50% of the original dose in an outpatient clinic. The persistence of these symptoms prevented further dose reductions. Upon review of the available literature, several other cases were identified describing development of tinnitus upon discontinuation or tapering of a benzodiazepine. In weighing the risks and benefits of chronic benzodiazepine therapy, tinnitus must be considered as a rare but debilitating and long-term risk of benzodiazepine withdrawal. Providers must be prepared to individualize benzodiazepine tapers and be vigilant about emergence of withdrawal symptoms to prevent undue stress in patients.Abstract
Type: Work in Progress. Background: Schizophrenia spectrum disorders are a set of chronicEffectiveness of Paliperidone Palmitate One-Month Long-Acting Injection in Obese Versus Non-Obese Patients