Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers
ABSTRACT Venlafaxine is generally considered to be a dual 5-HT and NE reuptake inhibitor when it is used at doses above 75 mg/d in humans. While its 5-HT reuptake-inhibiting property has been demonstrated, some controversy still exists regarding the doses of venlafaxine required to inhibit NE reuptake. Healthy male volunteers received, on a double-blind basis, paroxetine (20 mg/d), desipramine (100 mg/d), nefazodone (300 mg/d), or venlafaxine (150 or 300 mg/d) in the last 5 d of a 7-d period of administration. Inhibition of 5-HT reuptake was estimated by determining the degree of depletion of whole-blood 5-HT, while that of NE was assessed by measuring the attenuation of the systolic blood pressure increases produced by intravenous injections of tyramine. Paroxetine, both regimens of venlafaxine, and to a lesser extent desipramine significantly decreased whole-blood 5-HT content. Nefazodone failed to produce any significant change. Desipramine abolished the tyramine pressor response, whereas all other drug regimens left this parameter unaltered. Venlafaxine and paroxetine acted as potent 5-HT reuptake inhibitors in the present study. In contrast, neither the moderate nor the high dose of venlafaxine displayed any significant inhibiting activity in this model assessing NE reuptake in peripheral NE terminals. The validity of the model was confirmed by the potent inhibitory action of desipramine on NE reuptake. While the reasons for this unexpected lack of action remain unclear, venlafaxine appeared to be an effective NE reuptake agent in depressed patients using the same approach.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Levomilnacipran (LVM, Fetzima(®)) was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. It is a unique dual neurotransmitter reuptake inhibitor. In contrast with other selective serotonin norepinephrine reuptake inhibitors, including duloxetine, venlafaxine, and desvenlafaxine, it has greater selectivity for inhibiting norepinephrine reuptake than serotonin reuptake. Our review focuses on the efficacy, safety, and tolerability data for five double-blind, placebo-controlled, short-term studies and two long-term studies. In the short-term studies, LVM was found to be more effective than placebo in reducing depression (Montgomery-Åsberg Depression Rating Scale) scores as well as improving functional impairment (Sheehan Disability Scale) scores. Long-term studies found LVM to be similarly effective but in the only placebo-controlled long-term study, LVM was not significantly superior to placebo. LVM is fairly well tolerated, with the most common adverse events being nausea, headache, dry mouth, hyperhidrosis, and constipation. Discontinuation rates were mildly increased in those being treated with LVM (9%) versus placebo (3%). Adverse events were not dose-related except for urinary hesitancy and erectile dysfunction. LVM was weight neutral, was not toxic to the liver, and did not cause clinically significant QTc prolongation. Consistent with being a predominant potentiator of norepinephrine, pulse and blood pressure were significantly elevated by LVM but rarely induced tachycardia or hypertension. LVM is a relatively safe alternative antidepressant treatment with minimal drug-drug interactions. It is the only antidepressant that has in its labeling that it is not only effective in improving depression but also effective in improving impaired functioning. Whether this important effect on functioning is unique to LVM must be researched. In addition, whether LVM might be effective in norepinephrine-deficit depression, refractory depression, atypical depression, or seasonal depression is yet to be evaluated. Ultimately, head-to-head studies comparing LVM with other antidepressants will determine the place of LM in antidepressant treatment.Neuropsychiatric Disease and Treatment 01/2015; 11:125. DOI:10.2147/NDT.S54710 · 2.15 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Objective Few studies have compared simultaneously different antidepressants in long-term treatment of major depressive disorder (MDD). Long-term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects). Methods One hundred and fifty outpatients with an MDD diagnosis, treated with antidepressants in mono-therapy, were included. Follow-up period was set at 24months, and information have been obtained from charts, interviews with patients and their relatives, and from the Lombardy regional register. A survival analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations, or discontinuation due to side effects as death' events. ResultsIn our sample, 48.7% of the patients presented a recurrence within the first 2years of treatment. Bupropion appears less effective in long-term treatment of MDD than the other compared antidepressants, with exception of fluoxetine (p=0.09), amitriptyline (p=0.13), fluvoxamine (p=0.83), venlafaxine (p=0.5), and trazodone (p=0.58). Fluvoxamine appears to be less effective than citalopram (p=0.036), paroxetine (p=0.037), clomipramine (p=0.05), sertraline (p=0.011), and duloxetine (p=0.024). Conclusions Bupropion and fluvoxamine appear less effective in long-term treatment of MDD. These results should be confirmed by randomized placebo-controlled prospective studies with larger samples. Copyright (c) 2014 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 01/2015; 30(1). DOI:10.1002/hup.2447 · 1.85 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: To describe the clinical effect and safety of low-dose buprenorphine, a κ-opioid receptor antagonist, for treatment-resistant depression (TRD) in midlife and older adults.The Journal of Clinical Psychiatry 08/2014; 75(8):e785-93. DOI:10.4088/JCP.13m08725 · 5.14 Impact Factor