Bradley M. Wright

Augmentation with Atypical Antipsychotics for Depression: A Review of Evidence‐Based Support from the Medical Literature

Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5–26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy.

A review of insulin pen devices.

Abstract Optimization of glycemic control is a fundamental aspect of diabetes management, and rates of diabetes-related microvascular complications are significantly decreased when glycemic control is improved. Currently, > 5 million Americans require insulin therapy to manage their diabetes, and this number is expected to multiply as the prevalence of type 2 diabetes increases secondary to several factors. The distinct pharmacodynamic properties of each insulin product help physicians decide which type of insulin is the most appropriate for each patient. The method of delivery that will ensure both patient and provider satisfaction must also be carefully considered. Insulin pen devices are designed to provide a convenient and easy means of insulin administration for the patient and can be divided into 2 categories: the reusable, durable pen, and the disposable, prefilled pen. These insulin pen devices are an alternative to the traditional insulin vial-and-syringe method and offer many advantages. Insulin pens have also been found to be less painful than the vial-and-syringe method and are often associated with greater patient preference and social acceptability. As a result, this method of insulin delivery may ultimately help to improve glycemic control and should be considered when prescribing insulin products.

Alternate-Day Statin Therapy for the Treatment of Hyperlipidemia

Objective: To evaluate the safety, efficacy, and cost of alternate-day statin therapy in the treatment of hyperlipidemia. Data Sources: Systematic searches were conducted for primary literature sources involving alternative statin regimens using PubMed, EMBASE, Google Scholar, and International Pharmaceutical Abstracts (January 1966-March 2010). Articles selected were limited to those published in the English language. Reference citations from relevant publications identified were also reviewed. Study Selection and Data Extraction: All English-language articles identified were reviewed and 17 trials (14 prospective and 3 retrospective) involving alternate-day statin dosing were included. Studies involving alternative statin dosing regimens other than alternating days were excluded from this review. Data Synthesis: Daily administration of statins is the standard of therapy used to reduce low-density lipoprotein cholesterol (LDL-C) levels as well as atherosclerosis that may lead to coronary events. Through LDL-C lowering and pleiotrope effects, statins decrease cardiovascular morbidity and mortality. Unfortunately, due to cost and adverse effects of statins, some patients are nonadherent to statin therapy. Several small studies have found alternate-day statin therapy to be as effective at reducing LDL-C as daily administration, while also lowering the incidence of adverse reactions and potentially lowering cost. Conclusions: Alternate-day statin therapy may decrease cost and therapy-limiting adverse reactions while potentially increasing regimen adherence and positively affecting the lipid panel. Further research is needed to determine whether this alternative regimen produces similar cardiovascular outcomes as those with daily statin therapy,

Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid

Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs). Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

A Review of Insulin Pen Devices and Use in the Elderly Diabetic Population

The prevalence of diabetes mellitus (DM) in the elderly population currently represents almost one-half of the overall diabetic population. Treatment of DM often requires a multidrug regimen that includes insulin therapy; however, due to concomitant comorbidities such as dementia, vision loss, neuropathies, poor mobility, and poor manual dexterity, elderly patients may be at increase risk for hypoglycemia and other dosing errors that are associated with insulin administration. Insulin pen devices have been shown to provide more reliable, accurate, and simplified dosing, and therefore may be a safer, easier, and more acceptable method of insulin delivery in the elderly population. This review will describe the various insulin pen devices available today, as well as discuss the potential advantages of these devices in the elderly population.

Patterns of treatment modifications among newly treated hypertensive patients: Does choice of modification strategy affect likelihood of treatment discontinuation?

Objectives: Treatment modifications – addition, uptitration, switching, and downtitration – are necessary to address issues such as unattained blood pressure goals, adverse drug events, drug cost, or patient dissatisfaction which lead to treatment discontinuation. This study assessed the patterns of treatment modifications, and compared the rates of treatment modification and time-to-treatment modification across five antihypertensive drug classes (ADCs). Additionally, the association between treatment modification strategies and the likelihood of treatment discontinuation was assessed. Methods: This is a retrospective cohort study using the BlueCross-BlueShield of Texas commercial claims database (2008–2012). Treatment modifications that occurred within 1 year of starting hypertension treatment were identified. Patients who received treatment modifications were followed for 12 months to determine if and when they discontinued treatment. Cox regression models were used to determine the likelihood of treatment modification and treatment discontinuation. Results: About 48.5% of patients received treatment modifications within 1 year of treatment initiation. Rates of treatment modification were significantly different across ADCs; angiotensin-converting enzyme inhibitor and angiotensin receptor blocker users were less likely to receive treatment modifications compared with other ADCs. Mean time-to-treatment modification was more than 100 days for adding and uptitrating, and more than140 days for switching and downtitrating. Patients intensifying treatment by adding medications were about 25% (vs. uptitration) and 50% (vs. switching) less likely to discontinue treatment. Conclusion: Treatment modifications are common among newly treated hypertensive patients, and the rates vary significantly across ADCs. In the real world, treatment modifications occur much later than the 30-day timeline recommended by guidelines. Addition of drugs may be a preferred approach for intensifying treatment of patients at a high risk of treatment discontinuation.

Achieving Adherence After First-Line Antihypertensive Treatment: Should Fixed-Dose Combinations Receive Priority?

Data on the long‐term outcomes of the use of fixed‐dose combinations (FDCs) or free‐pill combinations (FPCs), titration of doses, and switching are currently unavailable for identifying a preferred strategy for adherence. In the lack of these evidences, adherence can be a useful guiding criteria. The authors conducted a retrospective cohort study using the BlueCross BlueShield of Texas (2008‐2012) database to compare adherence among 5998 patients who received treatment modifications (TMs). Results of the propensity score‐adjusted model indicate that FDC and uptitration strategies have higher odds of adherence compared with the switch strategy (P<.05). Among patients with a history of poor adherence, the odds of adherence were up to 26% higher for the FDC strategy compared with alternative strategies (P<.05). Factors including age, number of comedications, first‐line drug class, and health services utilization are associated with adherence. In conclusion, FDCs should be prioritized for TM, particularly if the patient has a history of poor adherence.

Evaluation and Pharmacologic Approach to Patients with Resistant Hypertension

Abstract Patients are diagnosed as having resistant hypertension when they have blood pressure readings that remain above goal despite the concomitant use of 3 optimally dosed antihypertensive agents from different classes, with 1 of the agents being a diuretic. Prior to diagnosing a patient as having resistant hypertension, it is important to document adherence and exclude white–coat hypertension, inaccurate measurement of blood pressure, and secondary causes of hypertension (eg, aldosterone excess). After determining resistance, optimization of the medication regimen is essential. Combination strategies, which might include dual renin–angiotensin–aldosterone blockade with spironolactone as 1 agent, have been proven successful. This article focuses on the safety and efficacy of spironolactone when added to an optimized 3–drug regimen. Additionally, the use of spironolactone in chronic kidney disease and obstructive sleep apnea complicated by resistant hypertension is discussed. These 2 clinical entities are frequently accompanied by resistant hypertension and are indications for the use of spironolactone as well.

Pharmacist Interventions Regarding the Appropriateness of Apixaban, Rivaroxaban, Dabigatran, and Warfarin in a University-Affiliated Outpatient Clinic:

Background: Direct oral anticoagulants (DOACs) have become available recently as an alternative to warfarin in appropriate patients. Few studies have been conducted that evaluate pharmacist-managed services for the management of the DOACs. Objective: To review the appropriateness of DOAC therapy and warfarin therapy in adult patients in a university-affiliated outpatient clinic and the need for further monitoring of these agents. Methods: A retrospective chart review was conducted of patients receiving a DOAC or warfarin therapy. Indication, dose, duration, age, weight, adherence, drug interactions, bleeding risk/history, renal function, and hepatic function were evaluated for DOACs and warfarin. If prescribed warfarin, international normalized ratio readings were also obtained. The pharmacists made verbal recommendations to primary care prescribers regarding findings, and changes to therapy were reviewed and documented. Results: A total of 175 patient charts were reviewed (49% DOACs, 51% warfarin). Twenty-five percent of prescribed DOACs should have been avoided due to inappropriate indication or renal function. The majority of these were switched to warfarin after discussion with the primary care provider. Of patients prescribed DOACs, 22% had a history of poor adherence to therapy and half of these were switched to warfarin. An additional 24% of prescribed DOACs were inappropriate due to incorrect dosing, major drug interactions, and/or renal dosing; however, these medications could be appropriate if adjustments are made. Nineteen percent of patients on warfarin therapy would be a candidate for DOAC therapy. Conclusion: Although there were limitations to this analysis, the results demonstrate that additional intervention is needed to improve appropriate prescribing and monitoring of the DOACs. Pharmacists can meet this need by providing medication reviews of novel anticoagulants and educating physicians.

Health Care Costs Associated with Addition, Titration, and Switching Antihypertensive Medications After First-Line Treatment: Results from a Commercially Insured Sample

BACKGROUND Treatment modifications are necessary for addressing issues related to efficacy and tolerance of first-line monotherapy, but they increase the economic burden on patients and their health plans. Understanding the differences in costs between alternative treatment modification strategies, if any, can serve as a guideline for clinical decision making and for designing cost-containment strategies. OBJECTIVE To compare the health care utilization costs between (a) addition (i.e., use of free-pill combinations [FPCs] or fixed-dose combinations [FDCs]) and uptitration as alternatives for addressing efficacy issues and (b) switching and downtitration as alternatives for addressing tolerance issues with first-line antihypertensive monotherapy. METHODS This is a retrospective cohort study that used the 2008-2012 BlueCross BlueShield of Texas claims database. Patients who had a treatment modification within 12 months of initiating antihypertensive monotherapy were identified. All-cause and disease-related health care utilization costs and drug costs were estimated from the BlueCross BlueShield health plans perspective over a 12-month period, starting from the date of treatment modification. Propensity score-adjusted generalized linear models were used to compare costs between alternative treatment modification strategies. RESULTS We identified 5,998 patients who met study criteria and had a modification of treatment: FPC (n = 1,395), FDC (n = 1,207), uptitration (n = 1,659), switching (n = 1,282), and downtitration (n = 455). All-cause and disease-related health services utilization costs were estimated for 12 months following treatment modification. Mean annual drug utilization costs were highest for the FDC strategy. All-cause inpatient and outpatient services utilization costs were significantly different between strategies used for addressing issues of tolerance and efficacy, respectively. Disease-related inpatient services utilization costs were lower for the FDC strategy compared with the uptitration strategy. However, disease-related inpatient services utilization costs were not significantly different for the downtitration strategy compared with the switch strategy. CONCLUSIONS Health care costs following treatment modifications vary by type of strategy. The high costs of FDCs may be offset by the reduction of inpatient services utilization costs. Careful consideration should be given to the differences in costs between alternative strategies. DISCLOSURES No outside funding supported this study. The dataset used in this study was created for dissertational research on the patterns and outcomes of treatment modification in hypertensive patients. Data and database support were provided by University of Texas School of Public Health/BlueCross BlueShield of Texas research program in payment systems and policy. Sonawane Deshmukh was an employee of Anthem BlueCross BlueShield from August 2015 to August 2016. Hansen has received consulting funds from Daichii Sankyo and has provided expert testimony for Allergan and Boehringer Ingelheim. All other authors have no known conflicts of interest. Study concept and design were contributed by Sonawane Deshmukh, Garza, Wright, and Hansen. Sonawane Deshmukh and Ganduglia Cazaban collected the data, and data interpretation was performed by Sonawane Deshmukh, Qian, Wright, and Zeng. The manuscript was written primarily by Sonawane Deshmukh, along with Qian and Garza, and revised by Sonawane Deshmukh, Qian, Ganduglia Cazaban, and Hansen.