Manouchkathe Cassagnol

Desvenlafaxine: A new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder

BACKGROUND Desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), was approved by the US Food and Drug Administration (FDA) in February 2008 for the treatment of adult patients with major depressive disorder (MDD). Desvenlafaxine is the third SNRI approved by the FDA for this indication. OBJECTIVE This article reviews the available information for desvenlafaxine, focusing on its pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile. METHODS A comprehensive search of MEDLINE (1950-March 2009), International Pharmaceutical Abstracts (1970-March 2009), ISI Web of Knowledge (1996-March 2009), and EMBASE (1974-March 2009) was conducted using the terms desvenlafaxine, O-desmethylvenlafaxine, and Pristiq. Reference lists of articles were reviewed for other relevant publications. Abstracts of unpublished clinical studies presented at the American Psychiatric Association annual meetings (2004-2008) were included in the review; also included were data from the FDA and the European Medicines Agency Web sites. RESULTS After oral administration, desvenlafaxine reaches T(max) in 7 to 8 hours and is slowly eliminated, with t((1/2)) values of 9 to 15 hours. With once-daily dosing, steady-state plasma concentrations are achieved within 4 to 5 days. Alternate-day dosing should be implemented in patients with severe renal impairment (creatinine clearance, < or =30 mL/min) and those with end-stage renal disease. In patients with moderate to severe hepatic impairment, daily doses should not exceed 100 mg. Nine short-term studies of desvenlafaxine have been conducted but only 8 were published. These 8 clinical studies evaluated oral desvenlafaxine 50 to 400 mg/d using randomized controlled trials for the treatment of MDD in adult outpatients. Significantly greater efficacy in the reduction of depressive symptoms was found in patients taking desvenlafaxine 50 mg/d (P < 0.05) compared with placebo. No additional therapeutic benefits were found at doses >50 mg/d. Preliminary data support desvenlafaxines efficacy and tolerability in the treatment of menopause-associated vasomotor symptoms. Desvenlafaxine was generally well tolerated in clinical trials; the most common adverse events were nausea, suicidal ideation, and changes in blood pressure and weight. CONCLUSIONS Desvenlafaxine 50 mg/d has been found to be efficacious and generally well tolerated in short-term trials for the treatment of adults with MDD. Further studies are needed to determine des-venlafaxines role in the management of MDD and its efficacy compared with other antidepressants.

Low-Dose Quetiapine Is Not a Benign Sedative-Hypnotic Agent

Second generation antipsychotics (SGAs) appear to be effective for a broad range of psychiatric disorders. When used in doses lower than those to treat psychosis, these agents are effective for anx...

The Therapeutic Use of Vaptans for the Treatment of Dilutional Hyponatremia

Hyponatremia is a very common electrolyte abnormality. Dilutional hyponatremia is very difficult to treat effectively due to the complications of conventional treatment. Arginine-vasopressin (AVP) plays an integral role in circulatory and water homeostasis. AVP is a hormone released in response to increases in plasma tonicity or decreases in plasma volume in an attempt to maintain the plasma osmolality between 284 and 295 mOsm/L. AVP receptor antagonists or “vaptans” are a new class of drugs that allow for the safe and efficacious treatment of dilutional hyponatremia. Conivaptan, a mixed V1a/V2 receptor antagonist, and tolvaptan, a selective V2 receptor antagonist, are the only 2 vaptans approved by the US Food and Drug Administration.

Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system

Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.

Use of the MDRD Study Equation for Drug Dosing

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