The terms racemic mixtures, single isomers, prodrugs, active metabolites, extended-release mechanisms were once remembered as the topics of early pharmacy school curriculum. Now they are often the source of confusion for practitioners and, sometimes, big money for manufacturers. Since 2011, nearly ten percent of the top 100 medications by sales were “new and improved” versions of previously released products with 4–5% being revised psychotropics.1 Since these “new” products are released as brand name agents under patent protection, they are often priced much higher than their predecessors. Clinical evidence is limited to approval trials – a handful of placebo-controlled
When ‘new’ psychotropic medications are released on the market, it can be difficult to discern the differences between the newer agents and their similar predecessors. Since head to head clinical trials are rarely available, it is important to learn what can be gleaned from the package inserts and the Food and Drug Administration (FDA) website. These sources are a wealth of information and were used as the primary resources for the comparative tables that follow.
Adderall XR® (MAS XR) and Vyvanse™ (LDX) are both schedule II amphetamine-based central nervous system stimulants indicated for the treatment of attention-deficit/hyperactivity disorder. Differences among the two primarily involve dosage form, pharmacokinetic profiles, and abuse potential. MAS XR and LDX are both long-acting stimulants with an approximate duration of action of 10 hours. The long-acting property of LDX is secondary to its prodrug formulation, whereas MAS XR utilizes bead filled capsules that mimic twice daily dosing upon administration. MAS XR is a substrate of CYP 2D6 while LDX does not utilize the cytochrome P450 enzymes for metabolism. There are few efficacy studies that directly compare LDX and MAS XR. There are no head to head abuse liability studies for MAS XR and LDX; however, the prodrug formulation of LDX is proposed to have lower abuse potential.
Antidepressant drug development first began in the mid-twentieth century with the discovery of monoamine oxidase inhibitors and tricyclic antidepressants. Soon after, additional molecular targets and drug entities were created, eventually leading to the development of selective serotonin reuptake inhibitors. Today, antidepressants now rank among the top 10 most commonly used medications in the United States (US) and account for over $11 billion in annual sales. To help ensure the safety and efficacy of these commonly used products, in 1977 the US Food and Drug Administration (FDA) created guidelines to standardize antidepressant studies and the approval process. Although many of the recommendations outlined by FDA are still relevant, the document remains vague when describing key aspects of antidepressant trial design and much of the clinical information is outdated by today's standards. This paper will provide a general overview of the FDA-approval process, summarize FDA's position related to antidepressant trial design, and discuss the need for updates in the approval process.
Buprenorphine and buprenorphine/naloxone sublingual tablets were approved by the FDA in 2002. In 2010, the buprenorphine/naloxone sublingual film was approved to address concerns of diversion, time for tablet dissolution, and unintentional exposure in children with the tablet. This article will compare the buprenorphine sublingual formulations in terms of pharmacokinetics, safety, diversion and misuse, cost, and patient preference. It will explore current data suggesting advantages or disadvantages of the various formulations since conclusive data are minimally available.
After a long history of use for hypertension, clonidine and guanfacine have re-emerged on the market as treatment options for attention-deficit/hyperactivity disorder, particularly in patients who are unable to tolerate or need an alternative to stimulant medications as well as those who have residual symptoms despite adequate therapy with stimulants. In recent years, new formulations of long-acting clonidine and guanfacine have come to market. The purpose of this article is to review the pharmacokinetic properties and clinical utility of these new agents while comparing the medications and parent compounds in terms of dosing, adverse effects, and costs of treatment.
Levomilnacipran (Fetzima™) was approved by the United States Food and Drug Administration (FDA) in July 2013 for the treatment of Major Depressive Disorder (MDD) in adults. Levomilnacipran is the (1S,2R) enantiomer of racemic milnacipran and represents one of the newest medications designed and marketed as an enantiomer of an already approved medication with hopes of improving efficacy and limiting side effects. This article reviews the evidence supporting the use of milnacipran for MDD, examines the clinical studies behind levomilnacipran's approval, and discusses practical considerations regarding the use of this new antidepressant medication.
There is a modest collection of literature describing the pharmacokinetic and clinical differences between the extended-release form of divalproex sodium (Depakote ER®) and the delayed-release form (Depakote®). Published articles are quick to espouse the extended-release formulation, especially in the setting of seizure control. Reasons commonly cited include a longer dosing interval, improved patient compliance, a more consistent pharmacokinetic profile, and fewer side effects. There are fewer articles discussing these differences in the context of treating mental illnesses, namely bipolar affective disorder. This article aims to compare these two formulations of divalproex with a special focus on their pharmacokinetic profiles, uses in psychiatric illness, and the role of therapeutic drug monitoring. The patient case that follows will describe a scenario in which a patient was prescribed each formulation during an acute hospitalization.