Pharmacological treatment for generalized anxiety disorder in adults: an update.

INTRODUCTION: Modest response and remission rates for the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, coupled with mounting evidence that the tolerability of the antidepressants (ADs) may have been overstated in the literature, has contributed to changes in prescribing patterns for generalized anxiety disorder (GAD). New interest in the absence of evidence that supports these standard therapies as superior to benzodiazepines stimulated a review of the literature. AREAS COVERED: A literature search was conducted in the MedLine database with search terms 'generalized anxiety disorder' and 'treatment' for purposes of including relevant literature related to pharmacologic treatment of GAD. Aside from a review of pivotal literature, the authors also included newer studies that evaluated novel drug treatments. Last, the database was searched for benzodiazepine comparisons to standard therapy secondary to concerns that such literature is sparse. The review of newer modalities and the decision to include related literature was also based on the strength of the evidence and the status of their approval for the treatment of GAD. EXPERT OPINION: Although ADs remain the most frequently prescribed medications for GAD, alternative and off-label therapies such as pregabalin, the atypical antipsychotics and vortioxetine are garnering interest. Based on the evidence available to us, it is our recommendation that along with the ADs, benzodiazepines be considered a possible first-line therapy in eligible patients based on the discretion and clinical judgment of the treating physician.

Assessing Medicare Beneficiary Eligibility for Medication Therapy Management Programs Using PINNACLE, a National Cardiovascular Data Registry.

BACKGROUND: Medication therapy management (MTM) is a mandated component of the 2003 Medicare Modernization Act for Part D prescription drug plans and Medicare Advantage plans, authorizing the pharmacist or other qualified provider to identify, resolve, and prevent medication-related problems for patients with chronic diseases. MTM programs have been shown to improve medication adherence and reduce medication errors while reducing overall costs in patients with cardiovascular (CV) disease; however, MTM has been greatly underutilized for patients with chronic diseases. OBJECTIVE: To identify the proportion of Medicare beneficiaries who are eligible for, and who could potentially benefit from, participating in MTM among patients enrolled in the National Cardiovascular Data Registry's PINNACLE Registry. METHODS: Patient MTM eligibility is based on the presence of multiple chronic diseases and meeting a minimum annual insurance medication costs. We used patient data from 462 academic and private cardiology practices in the United States who participated in the PINNACLE Registry between May 1, 2008, and September 30, 2010, to determine Medicare beneficiaries' eligibility to participate in an MTM program for patients meeting the MTM criteria of (1) a number of chronic diseases (in this case, the number of CV conditions) and (2) an estimated minimum annual medication expenses, using a weighted average cost calculated based on the average wholesale price of the most often prescribed medications, by class, as extracted from the HealthCore Integrated Research Database and weighted according to prescribing frequency within a class. RESULTS: Among the Medicare beneficiaries in the PINNACLE Registry, 93,089 (58%) had ≥3 chronic CV conditions, and the median annual estimated medication expenditure per patient enrolled in the PINNACLE Registry was $1329. Of the total of 93,089 Medicare beneficiaries, 21.4% were eligible for MTM, based on the 2010 minimum eligibility criterion of an annual insurer medication expenditure of $3000 or more. These costs ranged from $366 for low-cost generics to $3958 for the highest-cost drug in a class. In addition, based on the 2010 minimum eligibility rule, the proportion of patients eligible for MTM ranged from 7.9% for those eligible for MTM for low-cost generics to 64% of patients eligible for MTM for the highest-cost medication in a class. CONCLUSIONS: These data serve to raise awareness regarding patients' potential eligibility to receive the benefits of MTM programs. Providers caring for patients with multiple CV conditions, including specialists such as cardiologists, should explain to eligible patients about MTM programs and encourage these patients to take advantage of such programs.

Evidence for the use of vilazodone in the treatment of major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is characterized by dysfunction in cognition, behavior, and physical functioning, and is associated with a chronic clinical course. There are barriers to successful treatment, which often result in early discontinuation and relapse. Adverse effects (AEs) remain the most commonly cited reason for discontinuation of treatment with conventional antidepressants, particularly early on in therapy. This often translates into relapse of symptoms or recurrence of the depressive episode. The delay to therapeutic response also has a meaningful implication for treatment adherence. AREAS COVERED: This article focuses on the implications of a novel entity for the treatment of depression; the first new molecule developed for this indication in the last 10 years. Vilazodone is a novel dual-acting serotonergic antidepressant, which is a selective and potent inhibitor of serotonin reuptake, as well as a selective partial agonist of the 5-HT(1A) receptor. EXPERT OPINION: The data available in the literature so far indicate clinical efficacy over placebo and a rather benign adverse event profile. Whether the early onset of clinical efficacy observed in one of the two pivotal studies represents a true or only a chance phenomenon, only future studies can tell. Adverse effects are mostly mild-moderate and most GI type AEs disappear in about one week, at a time when all patients are still on a clinically suboptimal daily dosage (10 mg/d during the first week). Sexual AEs did not differ from placebo. Vilazodone represents an interesting addition to the arsenal of available antidepressants.

Pharmacological treatment of generalized anxiety disorder.

INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic, relapsing, debilitating disorder, associated with markedly impaired social and occupational functioning. Pharmacological treatment is considered standard care and several drug classes are now FDA approved for the treatment of GAD. While there are clear data for the efficacy of short-term acute treatment, long-term treatment and treatment-resistant GAD remain challenging. AREAS COVERED: This article describes current pharmacological treatment options for GAD, with focus on benzodiazepines, azapirones, antidepressants and anticonvulsant and antipsychotic drugs. Recent findings from placebo-controlled clinical trials are reviewed and evidence-based clinical implications are discussed. A PubMed search was completed using the terms: 'generalized anxiety disorder AND treatment' and 'generalized anxiety disorder AND therapy'. Additional pivotal trials were included for a historical perspective (older landmark trials that established efficacy and safety for older drug classes in the treatment of GAD). EXPERT OPINION: Efficacy for treatment of GAD has been established for several different drug classes. At present, based on clear efficacy and good tolerability, first-line treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is indicated. If an initial, at least moderate, clinical response is achieved under antidepressant therapy, treatment should be at least continued for 12 months.

Torsades de pointes associated with methadone and voriconazole.

This report concerns a case of torsades de pointes (TdP) associated with the concomitant administration of methadone and voriconazole in a patient with comorbid medical conditions. A 57-year-old man, with a medical history of human immunodeficiency virus, infective endocarditis, hepatitis C and orbital Aspergillus infection, was admitted to the intensive care unit following several episodes of TdP. The patient was being treated with methadone for opioid addiction and had started taking voriconazole 2 weeks prior for orbital Aspergillosis. He experienced multiple episodes of TdP with a prolonged QTc interval (>600 ms). The pronounced inhibitory impact of voriconazole on methadone metabolism via the cytochrome P450 (CYP)2B6 isoenzyme was identified as a probable cause of the arrhythmia. Voriconazole was subsequently temporarily withheld and the methadone dose was significantly reduced. The patient received an implantable cardioverter-defibrillator, did not experience additional episodes of TdP during hospitalisation, and was discharged from the hospital on day 13.