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Indication and Clinical Profile

Vilazodone is the newest selective serotonin reuptake inhibitor (SSRI) approved for the treatment of major depressive disorder (MDD). MDD, affecting nearly 19 million people in the U.S., is characterized by depressed mood, loss of interest in usual activities, significant change in weight or appetite, sleep disorders, increased fatigue, impaired concentration, and suicidal thoughts or behavior. The most commonly prescribed drugs for MDD are SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs). These agents are preferred because of their relative efficacy and safety and because they are less toxic in overdose than older antidepressants (i.e., tricyclics and monoamine oxidase inhibitors [MAOIs]).

Approval of vilazodone was based on two 8-week, multicenter, randomized, double-blind, placebo-controlled studies in 869 adults with MDD who received either vilazodone titrated over 2 weeks to a dosage of 40 mg or placebo once daily. Vilazodone was superior to placebo in the improvement of depressive symptoms as measured by the mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score.

Pharmacology and Pharmacokinetics11,12

Vilazodone is a indole-piperazine (FIGURE 6) that functions as an SSRI and 5-HT1A receptor partial agonist. It has negligible affinity for other serotonin receptors. Vilazodone's antidepressant effects are thought to be due to enhancement of serotonergic activity in the central nervous system (CNS) through selective inhibition of serotonin reuptake. The contribution of vilazodone's 5-HT1A receptor partial agonist activity is unknown.

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The absolute bioavailability of vilazodone is 72% when the drug is taken with food. Vilazodone is extensively metabolized through CYP and non-CYP pathways, with less than 2% of the dose excreted in the urine and feces as unchanged vilazodone. CYP3A4 is primarily responsible for vilazodone's metabolism, with minor contributions from CYP2C19 and CYP2D6. Strong inhibitors of CYP3A4 can reduce the metabolism of vilazodone and increase exposure, while CYP3A4 inducers can decrease exposure. Vilazodone does not appear to significantly inhibit or induce the metabolism of other CYP drug substrates (except for CYP2C8).

Adverse Reactions and Drug Interactions11,12

The most frequent adverse reactions reported by patients taking vilazodone in clinical trials were diarrhea, nausea, vomiting, and insomnia. Vilazodone has a rate of sexual side effects and weight gain comparable to placebo. All antidepressants have a black box warning and a patient medication guide describing the increased risk of suicidal thinking and behavior in children, adolescents, and young adults aged 18 to 24 years during initial treatment. Neonates exposed to serotonergic antidepressants late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with vilazodone, consideration should be given to whether the potential benefits outweigh the potential risks of treatment (Pregnancy Category C).

The dosage of vilazodone should be reduced when the drug is coadministered with CYP3A4 strong inhibitors. Concomitant use of vilazodone with CYP3A4 inducers can result in inadequate drug concentrations and may diminish effectiveness. Vilazodone should not be used concurrently with an MAOI or within 14 days of stopping or starting an MAOI. SSRIs can increase the occurrence of upper GI bleeding, and concurrent use of a nonsteroidal anti-inflammatory drug (NSAID) or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Thus, patients taking warfarin should be carefully monitored when vilazodone is initiated or discontinued. The risk of vilazodone administered in combination with other CNS-active drugs has not been systematically evaluated; therefore, caution is advised in the case of concurrent use.

Dosage and Administration11,12

Vilazodone is available as 10-mg, 20-mg, and 40-mg tablets. The recommended dosage of vilazodone is 40 mg once daily. Treatment should be titrated, with an initial dosage of 10 mg once daily for 7 days followed by 20 mg once daily for an additional 7 days and then an increase to 40 mg once daily. No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment or with mild or moderate hepatic impairment. The vilazodone dosage should be reduced to 20 mg when the drug is coadministered with CYP3A4 strong inhibitors.

The efficacy of vilazodone has not been investigated beyond 8 weeks. Thus, patients should be reassessed periodically to determine the need for maintenance treatment and the appropriate treatment dosage.


5HT機轉:圖解藥理學~23serotonin


床數據公司(NASDAQ:CLDA)今天宣布,美國食品和藥物管理局(FDA)已批准vilazodone鹽酸片,將市場上銷售的品牌名稱 Viibryd™,用於治療成年人抑鬱症(MDD )。 Viibryd是一種新的分子實體和第一個也是唯一的選擇性血清素再攝取抑製劑和5HT 1A受體的部分激動劑。臨床數據計劃使Viibryd可在美國藥店在今年第二季度。

“這也是第一個藥物,該公司已開發,並已收到來自 FDA的上市批准在其第一次審查是一個顯著的里程碑臨床數據。”

“在治療 MDD,我們的目標是提供治療方案,以滿足個性化需求的每一個病人,說:”斯蒂芬M斯塔爾,醫學博士,精神病學教授,美國加州大學聖地亞哥分校。 “Viibryd是一個重要的新的治療選擇被證明療效和安全性證明。”

該機制的抗抑鬱作用Viibryd尚不完全清楚,但被認為是關係到其增強的血清素活動在中樞神經系統(CNS)通過選擇性抑制血清素再攝取。 Viibryd也是部分激動劑在血清素1A受體5HT,但是,最終結果這個動作對血清素的傳輸,其作用在Viibryd的抗抑鬱作用是未知的。

在療效 Viibryd作為治療 MDD成立於兩個 8週,多中心,隨機,雙盲,安慰劑對照研究,成年人誰符合標準的MDD。在這些研究中,患者被滴定了兩個多星期的劑量為 40毫克Viibryd每日一次。Viibryd優於安慰劑在改善抑鬱症狀,測得的平均變化從基線到第8週在蒙哥馬利 - Asberg抑鬱量表(MADRS)的總成績。

Viibryd被證明是安全的臨床研究。在安慰劑對照,Ⅲ期研究中,最常見的不良反應 Viibryd治療的患者是腹瀉,噁心,嘔吐和失眠。沒有一個單一的不良事件導致停藥治療在大於 1%的患者。總體而言,7.1%的病人誰收到Viibryd停止治療,由於不良反應,而3.2%的安慰劑治療的患者。 Viibryd尚未與任何臨床重要的變化在實驗室的測試參數,包括肝功能檢查,包括心電圖 QT間期,或生命體徵。此外,Viibryd沒有影響體重作為衡量從基線的平均變化在8週的研究。其中常見的不良反應(≥2%)與性功能與 Viibryd相比安慰劑性慾下降(4%和<1%),異常高潮(3%對 0%),延遲射精(2%對0%,男性只),和勃起功能障礙(2%和1%,男性只)。

“雖然目前現有的治療方法為 MDD,沒有人療法適用於每一位病人的副作用概況和變化,這可能會影響雙方遵守和治療成功,說:”卡羅爾 R.里德醫師,執行副總裁兼首席醫療官的臨床數據。 “Viibryd將是一個新的選擇的醫療機構和患者誰患有抑鬱症。”

Viibryd是唯一的抗抑鬱藥是一種選擇性血清素再攝取抑製劑和5HT 1A受體的部分激動劑,說:”德魯Fromkin,總裁兼首席執行官的臨床資料。 “這也是第一個藥物,該公司已開發,並已收到來自 FDA的上市批准在其第一次審查是一個顯著的里程碑臨床數據。”

 

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