Vilazodone

Vilazodone

Clinical data
Pronunciation	/vɪˈlæzədoʊn/ vi-LAZ-ə-dohn
Trade names	Viibryd
Other names	EMD-68843; SB-659746A
AHFS/Drugs.com	Monograph
MedlinePlus	a611020
License data	US DailyMed: Vilazodone
Routes of administration	By mouth
Drug class	Serotonin modulator[1]
ATC code	N06AX24 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[2] CA: ℞-only[3][4] US: ℞-only[5]
Pharmacokinetic data
Bioavailability	72% (oral, with food)[5]
Metabolism	Liver via CYP3A4[5]
Elimination half-life	25 hours[5]
Excretion	Faecal and renal[5]
Identifiers
IUPAC name 5-(4-[4-(5-Cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide
CAS Number	163521-12-8 N as HCl: 163521-08-2
PubChem CID	6918314 as HCl: 6918313
IUPHAR/BPS	7427
DrugBank	DB06684 as HCl: DBSALT000187
ChemSpider	5293518 Y as HCl: 5293517
UNII	S239O2OOV3 as HCl: U8HTX2GK8J
KEGG	D09698 Y as HCl: D09699
ChEBI	CHEBI:70707 N as HCl: CHEBI:70705
ChEMBL	ChEMBL439849 Y as HCl: ChEMBL1615374
PDB ligand	YG7 (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID80870086
Chemical and physical data
Formula	C26H27N5O2
Molar mass	441.535 g·mol−1
3D model (JSmol)	Interactive image
SMILES N#Cc5ccc4[nH]cc(CCCCN3CCN(c2ccc1oc(C(N)=O)cc1c2)CC3)c4c5
InChI InChI=1S/C26H27N5O2/c27-16-18-4-6-23-22(13-18)19(17-29-23)3-1-2-8-30-9-11-31(12-10-30)21-5-7-24-20(14-21)15-25(33-24)26(28)32/h4-7,13-15,17,29H,1-3,8-12H2,(H2,28,32) Y Key:SGEGOXDYSFKCPT-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder.^[1] It is classified as a serotonin modulator^[1] and is taken by mouth.^[1]

Common side effects include nausea, diarrhea, and trouble sleeping.^[1] Serious side effects may include increased suicidal thoughts or actions in those under the age of 25, serotonin syndrome, bleeding, mania, pancreatitis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).^[1] Vilazodone may cause less emotional blunting than typical selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs).^[6] A withdrawal syndrome may occur if the dose is rapidly decreased.^[1] Use during pregnancy and breastfeeding is not generally recommended.^[7] It is in the serotonin modulator class of medications and is believed to work both as an SSRI and activator of the 5-HT_1A receptor.^[1]

Vilazodone was approved for medical use in the United States in 2011^[1] and in Canada in 2018.^[8] In 2019, it was the 334th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions.^[9] The drug lost patent protection in June 2022 for adults and in July 2023 for pediatrics.^[10] Generic versions have been approved by the US Food and Drug Administration.^[11][12]

Seven controlled efficacy trials were conducted of vilazodone for treatment of major depressive disorder.^[13] Five of these trials showed no significant influence of vilazodone over placebo on depressive symptoms.^[13] In the remaining two trials, small but significant advantages of vilazodone over placebo were found.^[13] According to these two eight-week trials in adults, vilazodone has an antidepressant response after one week of treatment.^[14] After eight weeks it resulted in a 13% greater response than placebo.^[14] Remission rates, however, were not significantly different versus placebo.^[14]

According to the US Food and Drug Administration in 2011, "it is unknown whether vilazodone has any advantages compared to other drugs in the antidepressant class."^[15] A 2019 review stated that "present studies do not suggest the superiority of vilazodone compared with other antidepressants."^[16]

Development of vilazodone for generalized anxiety disorder has been stopped as of 2017.^[17] While there is tentative evidence of a small benefit in generalized anxiety disorder, there is a high rate of side effects.^[18]

In September 2016, the US Food and Drug Administration required a new warning to be added to the prescription label related to a link between vilazodone and acute pancreatitis and sleep paralysis.^[19]

The most common adverse effects include nausea, diarrhea, vomiting, and insomnia.^[5]

After a one-year, open-label study assessing the safety and tolerability of vilazodone in people with major depressive disorder, the most common adverse effects were diarrhea (35.7%), nausea (31.6%), and headache (20.0%); greater than 90% of these adverse effects were mild or moderate.^[20][14] In randomized controlled trials, meanwhile, these rates were 28%, 23.4% and 13.3%, respectively.^[14] In contrast to other selective serotonin reuptake inhibitors (SSRIs), initial trials showed that vilazodone did not cause decreased sexual desire/function, which often cause people to abandon their use.^{[21][unreliable medical source?]} Additionally, vilazodone may cause less emotional blunting than typical SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs).^[6]

Antidepressant exposure (including vilazodone) is associated with shorter average duration of pregnancy (by three days), increased risk of preterm delivery (by 55%), lower birth weight (by 75 g), and lower Apgar scores (by <0.4 points).^[22][23] It is uncertain whether there is an increased rate of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy.^[24][25]

Vilazodone acts as a serotonin reuptake inhibitor (IC₅₀ = 2.1 nM; K_i = 0.1 nM) and 5-HT_1A receptor partial agonist (IC₅₀ = 0.2 nM; IA = ~60–70%).^[14][26] It has negligible affinity for other serotonin receptors such as 5-HT_1D, 5-HT_2A, and 5-HT_2C,^[26][27] as well as the norepinephrine and dopamine transporters (K_i = 56 nM for NET and 37 nM for DAT).^[5] A small clinical study found occupancy of the 5-HT_1A receptor with vilazodone, whereas occupancy of the SERT by vilazodone in humans does not seem to have been studied.^[28][29][30]

Vilazodone is best absorbed with food and has a bioavailability of 72% under fed conditions. The C_max increased between 147 and 160% and the AUC increased between 64 and 85% of vilazodone when it was administered with either a fatty or light meal.^[31]

It was developed by Merck KGaA and licensed by Clinical Data, a biotech company purchased by Forest Laboratories in 2011.^[32]