Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.
Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.
Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD. 相似文献
The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice. 相似文献
Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache. 相似文献
Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT1c and 5-HT2 receptor subtypes and to 5-HT uptake sites (IC50 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT2 receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [3H]-5-HT uptake and a dose-dependent down-regulation of 5-HT2 receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT2 receptors, which could contribute to its antidepressant effect. 相似文献
Summary The effects of a single administration (48 hours) and of chronic (14 days) treatment with tricyclic (desipramine, nortryptiline) and nontricyclic (mianserin, nomifensine) antidepressant drugs on responses of the isolated anococcygeus muscle to the 2-adrenoceptor agonist xylazine (inhibition of contraction to field stimulation at 1 Hz) and to the 1-adrenoceptor agonist phenylephrine (contraction of the muscle) have been studied.Of the drugs used only desipramine and nortryptiline administered chronically reduced the responsiveness of the anococcygeus muscle to phenylephrine suggesting a desensitization of postsynaptic 1-adrenoceptors. Long-term but not acute administration of antidepressants resulted in significant decrease in sensitivity of presynaptic 2-adrenoceptors to xylazine. These results show that the adaptative changes of -adrenoceptors in the rat anococcygeus muscle following long-term administration may depend on the efficiency to inhibit the neuronal uptake and the ability to antagonize 1-adrenoceptors. 相似文献
Summary The 2 major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol-sulphate (DOPEG-SO4) and free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG), both their endogenous concentrations and their accumulation from the NE-precursors 3H-tyrosine or 3H-dopamine, were determined in the whole rat brain to assess the effect of chronic treatment with desipramine (DMI), imipramine and amitriptyline. DOPEG-SO4 was decreased 2 h and 24 h after the last administration of DMI (10 mg/kg twice daily for 4, 10 or 20 days) or imipramine (10 mg/kg twice daily for 10 days). When measured within 24 h after the last dose of DMI or imipramine, several schedules resulted in reduced accumulation of total-3H-MOPEG and 3H-NE, while 3H-NE and MOPEG were unchanged in the remaining schedules. These results indicate that DMI retains its ability to decrease NE-turnover over a period of 20 days of treatment. Forty-eight hours or 72 h after the last administration of desipramine and imipramine an overshoot was observed in NE-metabolism, consisting of increased levels of total-3H-MOPEG and endogenous total-MOPEG; DOPEG-SO4 was some-times concomitantly increased. The overshoot was more consistent after 20 or 10 days of treatment than after 4 days of treatment. This finding, together with a tendency to partial tolerance to the metabolite decreasing effects of DMI, indicate that adaptive changes occur in the NE system after treatment for 10–20 days with DMI or imipramine.Abbreviations Used NE
norepinephrine
- DOPEG
3,4-dihydroxyphenylglycol
- DOPEG-SO4
DOPEG sulphate ester
- MOPEG
3-methoxy-4-hydroxyphenylglycol
- total-MOPEG
free plus conjugated MOPEG
- DOPAC
3,4-dihydroxyphenylacetic acid
- HVA
homovanillic acid
- NM
normetanephrine
- DA
dopamine
- DMI
desipramine 相似文献