Limited evidence exists evaluating the impact of gabapentin in conjunction with benzodiazepines for the management of alcohol withdrawal. A review of outcomes associated with combination gabapentin and benzodiazepine therapy may illuminate new therapeutic uses in clinical practice. This retrospective study evaluated the impact of gabapentin on as-needed use of benzodiazepines in inpatients being treated for acute alcohol withdrawal. The treatment cohort consisted of patients prescribed gabapentin while on a symptom-triggered alcohol withdrawal protocol. The control cohort consisted of patients on symptom-triggered alcohol withdrawal protocol without concurrent gabapentin use. Secondary objectives included length of hospital stay, duration on alcohol withdrawal protocol, frequency of complicated withdrawal, and use of additionally prescribed as-needed or scheduled benzodiazepines. The gabapentin cohort was on the alcohol withdrawal protocol for a similar duration, compared with the control cohort (median of 4 [interquartile range: 2,6] days vs 3 [2,4] days, P = .09, respectively). Similarly, the gabapentin cohort required a median of 1 [1,2] benzodiazepine dose for alcohol withdrawal symptoms compared with a median of 1 [1,2] dose in the control cohort, P = .89. No significant difference was found between cohorts for as-needed and scheduled benzodiazepine use. Length of stay in hospital was similar between groups. These results suggest that gabapentin use, in conjunction with benzodiazepines, impacts neither the time on alcohol withdrawal protocol or the number of benzodiazepine doses required for withdrawal. Larger, prospective studies are needed to detect if gabapentin alters benzodiazepine usage and to better elucidate gabapentin's role in acute alcohol withdrawal.Abstract
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Antipsychotic use and fracture risk: An evaluation of incidence at a Veterans Affairs medical center
Recent meta-analyses have found a correlation between schizophrenia and increased fracture risk with one contributing factor potentially being antipsychotic-induced hyperprolactinemia, which may accelerate bone turnover. The objective of this study is to evaluate fracture rates in patients on long-term antipsychotic therapy to see if screening for osteoporosis should be included with routine monitoring. Patients exposed to antipsychotics for ≥3 months during a 10-year study period were included in this retrospective analysis. The primary outcome was to compare fracture rates in those exposed to long-term antipsychotics to a control group with similar demographics and comorbidities not receiving antipsychotics. Secondary outcomes included examining the risk of fracture by medication use and comorbid disease states associated with causing osteoporosis, vitamin D level monitoring and fracture presence, and the time to first fracture. Long-term use of antipsychotics was not associated with an increased rate of fractures compared to the control group in this study. End-stage renal disease, tobacco use, alcohol use, glucocorticoids, antiepileptics, and proton pump inhibitors were associated with higher risk of fracture (P < .05). Vitamin D level monitoring and supplementation was found to be a protective factor and lowered the risk of fracture. Long-term antipsychotic use is not associated with an increased risk of fractures. Further long-term prospective studies are necessary to further investigate this correlation. Screening for osteoporosis should follow guideline-driven recommendations for at-risk populations.Abstract
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Depression is a recognized cause of disability globally with a propensity to be comorbid in patients with diabetes, leading to poorer health-related outcomes. Although a number of studies have investigated the correlation between improvement in depression and chronic disease, none have reported on achievement of target doses of antidepressant therapies and diabetes control. The objective of this study is to determine the influence of antidepressant dosing optimization on reducing hemoglobin A1c (HbA1c). This was a retrospective cohort study of patients seen at CommUnityCare Health Centers who were initiated on an antidepressant and had uncontrolled diabetes (HbA1c > 7%). Eligible patients were followed for 12 months after initiation and separated into those who achieved target dose and those who did not. Patient health questionnaire scores were collected when available in an attempt to quantify change in depressive symptoms. A total of 178 patients met inclusion criteria with 76 achieving an optimal dose (target group) and 102 patients below optimal dose (control group) at the end of the study period. Patients in both groups were similar at baseline with an HbA1c of 9.29% compared to 9.24% in the target and control groups, respectively. At the end of the study period, more patients in the target group achieved an HbA1c < 7% (22.9%, n = 48 vs 4.3%, n = 23, respectively; P < .05). These results suggest that optimization of antidepressant dosing in patients with diabetes may lead to an increased likelihood of reaching goal HbA1c < 7% although correlation to improvement of depression remains unknown.Abstract
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Long-acting injectable (LAI) antipsychotics were developed to increase medication adherence in patients with schizophrenia. The US Food and Drug Administration (FDA)-approved LAI dosing provides guidance regarding oral antipsychotic supplementation. Previous studies have concluded concomitant use of oral and LAI antipsychotics requires further investigation. The aim of this study was to examine oral antipsychotic supplementation among patients receiving select second-generation LAIs. Patients were included if they were admitted to an inpatient psychiatric unit and received a second-generation LAI. The primary outcome was to determine the percentage of patients receiving oral antipsychotic supplementation prescribed in accordance with FDA recommendations. Secondary outcomes described oral supplementation prescribed in an inconsistent manner with FDA recommendations and identified patient-specific predictors associated with oral supplementation prescribed consistent with FDA recommendations. Of the 422 patients evaluated, 376 patients met inclusion criteria. Oral supplementation was prescribed in a manner consistent with FDA recommendations in 30% of patients. The following predictors were associated with oral supplementation prescribed in accordance with FDA recommendations: LAI initiation (odds ratio 1.868, 95% confidence interval 1.120-3.125) and the use of the once-monthly paliperidone LAI (odds ratio 20.278, 95% confidence interval 10.472-39.873). In the patient population evaluated, oral supplementation of LAI antipsychotics were prescribed in 30% of patients in a manner consistent with FDA recommendations. Of the patients who were prescribed oral antipsychotic supplementation inconsistent with FDA labeling, 223 patients were prescribed oral supplementation longer than the recommended duration and 8 patients received oral supplementation for a shorter duration than recommended.Abstract
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The veteran population has a high incidence of posttraumatic stress disorder (PTSD), which is associated with increased risk of hypertension and cardiovascular death. Ambulatory blood pressure monitoring (ABPM) can identify abnormal diurnal blood pressure (BP) patterns, which are associated with increased risk of cardiovascular events. The intent of this evaluation was to examine prior ABPM studies to determine whether veterans with PTSD are more likely to have abnormal nocturnal dipping patterns compared with the general veteran population. Retrospective chart review was performed on all archived ABPM studies and classified by nocturnal dipping status and BP control rates. Pertinent patient demographics of age, sex, concomitant PTSD, and use of selected PTSD therapies were identified at the time of ABPM study. Association between dipping status, BP control rates, and patient demographics were analyzed using appropriate statistical tests. A total of 470 ABPM studies were determined to be valid and included. There were no differences in the distribution of nocturnal dipping patterns in veterans with or without PTSD. Likewise, rates of nocturnal, awake, and 24-hour hypertension were similar between groups. In patients with PTSD who were treated with evening PTSD therapy, there was a higher rate of normal dipping status compared with those without treatment (66.7% vs 29.7%, P = .03). Veterans with PTSD had similar distributions of dipping patterns and rates of overall, awake, and nocturnal hypertension compared with the general veteran population. The association of nocturnal PTSD therapy prescription in patients with PTSD and higher rates of normal dipping status may warrant further investigation.Abstract
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Pharmacists have been called upon to be involved in suicide prevention efforts, but little is known regarding their attitudes, interest, and perceived skills in the area. The study was a voluntary, anonymous survey of pharmacists who attended a large end-of-year continuing education program sponsored by a school of pharmacy. The survey included the Attitudes to Suicide Prevention (ASP) Scale, items concerning interest in suicide prevention, and items from the suicide skills section of the Suicide Knowledge and Skills Questionnaire. The survey was completed by 227/297 (76.4%) pharmacists. The percentage of participants who expressed interest in direct involvement, indirect involvement, and receiving training in suicide prevention were 25%, 46%, and 56%, respectively. The mean total score on the ASP was 32.2 ± 5.5. Approximately 4% to 8% of participants agreed that they had the requisite training, skills, or support/supervision to engage and assist suicidal patients, and 22% agreed to feeling comfortable asking their patients direct and open questions about suicide. The ASP scores and items relating to perceived skills were correlated with interest in direct involvement in suicide prevention. There were some positive findings, but overall, the pharmacists who participated in this survey felt unprepared to be frontline clinicians in suicide prevention efforts. Further studies should be conducted to determine if these findings are generally reflective of the broader pharmacy community. If the profession is to have a serious role in suicide prevention, then adequate suicide prevention training for pharmacy students and pharmacists may be necessary.Abstract
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The lifetime risk of developing depression is 16.6%, however the risk is 2-fold in patients with diabetes. The rate of diabetes is much higher for the Marshallese than the general US population, with a prevalence ranging from 25% to 50%, however the prevalence of depression is not well defined among this minority group. The primary objective of this study was to obtain the rate of positive depression screenings, using the Patient Health Questionnaire-2 (PHQ-2), among adult Marshallese patients with diabetes. A retrospective chart review was performed for Marshallese adults receiving care in a student-led clinic in Northwest Arkansas. Marshallese adults with a documented PHQ-2 score and a diagnosis of type 1 or 2 diabetes, as outlined by the American Diabetes Association, were included. Demographic information was obtained from the medical records. The data were analyzed using descriptive statistics. The study included 96 patients. Ten patients scored a 3 or higher on the PHQ-2, indicating a positive screen. Of these, scores ranged from 3 to 6, with the majority of patients scoring 4 (N = 6). The average hemoglobin A1C for patients with a positive PHQ-2 score was 10.5%. This project identified a rate of 10.4% of patients with a positive PHQ-2 from the study sample. This finding is similar to the prevalence of depression for the general US population, however it is lower than rates cited in the literature for patients diagnosed with diabetes. Future studies should use Native Marshallese community health workers and focus groups to develop a multistep approach to obtain a culturally appropriate, translated tool with high sensitivity for patient response.Abstract
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Mirtazapine is an antidepressant with US Food and Drug Administration approval for management of major depressive disorder. Low doses of mirtazapine are often used for management of insomnia, with higher doses expected to provide more noradrenergic effect, and thus a higher degree of activation. If so, use of higher doses at bedtime may not be advisable and may worsen certain neuropsychiatric symptoms. No studies have been performed to evaluate these outcomes. This study consisted of a retrospective review of data submitted to the US Food and Drug Administration's Adverse Event Reporting System from January 1, 1995, to August 1, 2015. Cases that were deemed by study authors to represent activation of the noradrenergic system, and for which other confounders could not be identified, were included in the final analysis. The frequency of each specific adverse event was evaluated based on dose and compared to recent prescribing rates to determine if likelihood of a side effect increased with higher dose. The study identified 308 incidences of anxiety, agitation, delusion, hallucination, hypertension, insomnia, nightmare, or tachycardia. After controlling for frequency of prescribing at a given dose, there was a statistically significant increase in rates of tachycardia which correlated with dose. However, after correction for multiple comparisons, results were no longer significant. This study failed to support the hypothesis that mirtazapine is more activating at higher doses and appears to support the safety of increasing dose without increasing risk of noradrenergic side effects. Prospective studies will be necessary to confirm these findings.Abstract
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Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality. A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference. A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited. Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.Abstract
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Despite psychomotor restlessness and akathisia being an occasionally reported side effect of antidepressants as a class, and mirtazapine specifically, there is no general consensus on the best treatment approach. Propranolol may prove to be an effective treatment approach in patients who are not candidates for alternative therapies.Abstract