Desvenlafaxine Succinate: A Newer Antidepressant for the Treatment of Depression and Somatic Symptoms
Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.Postgraduate Medicine (Impact Factor: 1.7). 01/2010; 122(1):125-38. DOI: 10.3810/pgm.2010.01.2106
Desvenlafaxine succinate (DVS) is one of several serotonin-norepinephrine reuptake inhibitors (SNRIs). Others are venlafaxine hydrochloride, milnacipran, and duloxetine. Desvenlafaxine has been approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) based on a number of randomized, placebo-controlled clinical trials. Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg. Desvenlafaxine is currently the third SNRI approved by the FDA for this indication. Preliminary evidence also suggests the clinical usefulness of DVS in the treatment of vasomotor symptoms of menopause, anxiety symptoms, and painful physical symptoms. The modified pharmacokinetic and pharmacodynamic profiles of DVS differentiate this drug from the original product, venlafaxine. Significant points of difference, compared with venlafaxine, are once-daily dosing and the achievement of steady-state plasma concentrations within 4 to 5 days. To summarize, current evidence indicates that DVS has proven efficacy, acceptable safety and tolerability profiles, convenient dosing, and minimal impact on the cytochrome P450 enzyme system. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other selective serotonin noradrenaline reuptake inhibitors. Desvenlafaxine succinate has demonstrated its efficacy for treating MDD but its variable efficacy, as shown in individual studies, limited long-term data, and its different risk-to-benefit ratio compared with earlier antidepressants, means that further investigation of this drug is necessary.
- [Show abstract] [Hide abstract]
ABSTRACT: Even though noradrenaline has been recognized as one of the key neurotransmitters in the pathophysiology of major depression (MD), noradrenergic compounds have been less extensively utilized in clinical practice, compared to selective serotonin reuptake inhibitors (SSRIs). The development of the first selective noradrenergic reuptake inhibitor (NRI), Reboxetine, has not substantially changed the state of the art. In addition, Atomoxetine, a relatively pure NRI used for the treatment of ADHD, has shown mixed results when administered in augmentation to depressed subjects. Through a Medline search from 2000 to 2010, the present article provides an updated overview of the main pharmacological and clinical aspects of antidepressant classes that, partially or selectively, act on the noradrenergic systems. The noradrenergic action plays an important clinical effect in different antidepressant classes, as confirmed by the efficacy of dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) Bupropion, and other compounds (e.g., Mianserin, Mirtazapine), which enhance the noradrenergic transmission. In addition, many tricyclics, such as Desipramine and Nortriptyline, have prevalent noradrenergic effect. Monoamine oxidase inhibitors (MAOIs), moreover, block the breakdown of serotonin, noradrenaline, dopamine and increase the availability of these monoamines. A novel class of antidepressants--the triple reuptake inhibitors--is under development to selectively act on serotonin, noradrenaline, and dopamine. Finally, the antidepressant effect of the atypical antipsychotic Quetiapine, indicated for the treatment of bipolar depression, is likely to be related to the noradrenergic action of its metabolite Norquetiapine. Even though a pure noradrenergic action might not be sufficient to obtain a full antidepressant effect, a pronoradrenergic action represents an important element for increasing the efficacy of mixed action antidepressants. In particular, the noradrenergic action seemed to be related to the motor activity, attention, and arousal.
- [Show abstract] [Hide abstract]
ABSTRACT: A simple, sensitive, precise and stability indicating liquid chromatographic method has been developed for the estimation of desvenlafaxine succinate in pharmaceutical dosage form. A Hypersil C-18, 5 mu m-column with a mobile phase containing 0.05 M potassium dihydrogen phosphate:methanol (60:40 v/v), pH 7, was used. The flow rate was 1.0 mL/min and effluents were monitored at 226 nm. The retention time of desvenlafaxine was 7.4 min and the method was linear in the range of 0.1-20 mu g/mL. Desvenlafaxine stock solution was subjected to acid and alkali hydrolysis, chemical oxidation and dry heat degradation. The drug was found to be susceptible to base hydrolysis and developed method was found to give good separation between the pure drug and the degraded product. The method was successfully applied to the estimation of desvenlafaxine in tablet dosage forms.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.