Chemistry:Vilazodone

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Short description: Antidepressant medication
Vilazodone
Vilazodone.svg
Clinical data
Pronunciation/vɪˈlæzədoʊn/
vi-LAZ-ə-dohn
Trade namesViibryd
Other namesEMD-68843; SB-659746A
AHFS/Drugs.comMonograph
MedlinePlusa611020
License data
Routes of
administration		By mouth
Drug classSerotonin modulator[1]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability72% (oral, with food)[3]
MetabolismLiver via CYP3A4[3]
Elimination half-life25 hours[3]
ExcretionFaecal and renal[3]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC26H27N5O2
Molar mass441.535 g·mol−1
3D model (JSmol)
 ☒N☑Y (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 SIADH.[1] Vilazodone may cause less emotional blunting than typical SSRIs and SNRIs.[4] A withdrawal syndrome may occur if the dose is rapidly decreased.[1] Use during pregnancy and breastfeeding is not generally recommended.[5] It is in the serotonin modulator class of medications and is believed to work both as an SSRI and activator of the 5-HT1A receptor.[1]

Vilazodone was approved for medical use in the United States in 2011[1] and in Canada in 2018.[6] In 2019, it was the 334th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions.[7] The drug lost patent protection in June 2022 for adults and in July 2023 for pediatrics.[8] Generic versions have been approved by the U.S. Food and Drug Administration (FDA).[9][10]

Medical uses

Seven controlled efficacy trials were conducted of vilazodone for treatment of major depressive disorder (MDD).[11] Five of these trials showed no significant influence of vilazodone over placebo on depressive symptoms.[11] In the remaining two trials, small but significant advantages of vilazodone over placebo were found.[11] According to these two eight-week trials in adults, vilazodone has an antidepressant response after one week of treatment.[12] After eight weeks it resulted in a 13% greater response than placebo.[12] Remission rates, however, were not significantly different versus placebo.[12]

According to the US Food and Drug Administration (FDA) staff in 2011, "it is unknown whether vilazodone has any advantages compared to other drugs in the antidepressant class."[13] A 2019 review stated that "present studies do not suggest the superiority of vilazodone compared with other antidepressants."[14]

Development of vilazodone for generalized anxiety disorder (GAD) has been stopped as of 2017.[15] While there is tentative evidence of a small benefit in GAD, there is a high rate of side effects.[16]

Adverse effects

In September 2016, the FDA wrote a letter to Forest Labs requiring a new warning to be added to the label related to a link between the drug and acute pancreatitis and sleep paralysis.[17]

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.[12] In randomized controlled trials, meanwhile, these rates were 28%, 23.4% and 13.3%, respectively.[12] In contrast to other SSRIs, initial trials showed that vilazodone did not cause decreased sexual desire/function, which often cause people to abandon their use.[18] Additionally, vilazodone may cause less emotional blunting than typical SSRIs and SNRIs.[4] Incidence of adverse effects include:[3]

Very common adverse effects (incidence >10%)
  • Nausea
  • Diarrhea
  • Headache
Common adverse effects (1–10% incidence)


Uncommon adverse effects (0.1–1% incidence)


Rare adverse effects (<0.1% incidence)
  • Serotonin syndrome—a serious adverse effect characterised by:
    • Nausea
    • Vomiting
    • Mental status change (e.g. confusion, hallucinations, agitation, coma, stupor)
    • Muscle rigidity
    • Tremor
    • Myoclonus
    • Hyperreflexia—overresponsive/overactive reflexes
    • Hyperthermia—elevated body temperature
    • Autonomic instability (e.g. tachycardia, dizziness, abnormally excessive sweating, etc.)
  • Mania/hypomania—a potentially dangerously elated/agitated mood. Every antidepressant has the potential to induce these psychiatric reactions. They are particularly problematic in those with a history of hypomania/mania such as those with bipolar disorder.[19]
Unknown-incidence adverse effects
  • Suicidal ideation—all antidepressants can cause suicidal ideation especially in young adults and adolescents under the age of 25.
  • Abnormal bleeding—the SSRIs are known for their ability to increase the incidence of gastrointestinal bleeds and other bleeding abnormalities.[19][20][21]
  • Seizures
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)—a condition characterised by an abnormally excessive secretion of antidiuretic hormone causing potentially-fatal electrolyte abnormalities (such as hyponatraemia).
  • Hyponatraemia (a complication of the former)—low blood sodium.

Pregnancy

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]

Pharmacology

Pharmacodynamics

Vilazodone acts as a serotonin reuptake inhibitor (IC50 = 2.1 nM; Ki = 0.1 nM) and 5-HT1A receptor partial agonist (IC50 = 0.2 nM; IA = ~60–70%).[12][26] It has negligible affinity for other serotonin receptors such as 5-HT1D, 5-HT2A, and 5-HT2C,[26][27] as well as the norepinephrine and dopamine transporters (Ki = 56 nM for NET and 37 nM for DAT).[3] A small clinical study found occupancy of the 5-HT1A receptor with vilazodone, whereas occupancy of the SERT by vilazodone in humans does not seem to have been studied.[28][29][30]

Pharmacokinetics

Vilazodone is best absorbed with food and has a bioavailability of 72% under fed conditions. The Cmax 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]

History

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

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Vilazodone Hydrochloride Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/vilazodone-hydrochloride.html. 
  2. ↑ "Viibryd Product information". 25 April 2012. https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=92846. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Viibryd (vilazodone hydrochloride) tablet Viibryd (vilazodone hydrochloride) kit [Forest Laboratories, Inc."]. DailyMed. Forest Laboratories, Inc.. December 2012. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4c55ccfb-c4cf-11df-851a-0800200c9a66. 
  4. ↑ 4.0 4.1 "Adverse effects and treatment satisfaction among online users of four antidepressants". Psychiatry Research 255: 78–86. September 2017. doi:10.1016/j.psychres.2017.05.021. PMID 28531820. 
  5. ↑ "Vilazodone (Viibryd) Use During Pregnancy". https://www.drugs.com/pregnancy/vilazodone.html. 
  6. ↑ "Drug Product Database Online Query". Health Canada. Government of Canada. 25 April 2012. https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=92846#fn1. 
  7. ↑ "Vilazodone - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/VilazodoneHydrochloride. 
  8. ↑ "Generic Viibryd Availability". https://www.drugs.com/availability/generic-viibryd.html. 
  9. ↑ "Vilazodone: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022567. 
  10. ↑ "2019 First Generic Drugs Approvals". 21 January 2021. https://www.fda.gov/drugs/first-generic-drug-approvals/2019-first-generic-drug-approvals. 
  11. ↑ 11.0 11.1 11.2 "Antidepressants and the Placebo Effect". Zeitschrift für Psychologie 222 (3): 128–134. 2014. doi:10.1027/2151-2604/a000176. PMID 25279271. 
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 "A review of current evidence for vilazodone in major depressive disorder". International Journal of Psychiatry in Clinical Practice 17 (3): 160–169. August 2013. doi:10.3109/13651501.2013.794245. PMID 23578403. 
  13. ↑ "Vilazodone: clinical basis for the US Food and Drug Administration's approval of a new antidepressant". The Journal of Clinical Psychiatry 72 (9): 1166–1173. September 2011. doi:10.4088/JCP.11r06984. PMID 21951984. 
  14. ↑ "Evaluation of vilazodone for the treatment of depressive and anxiety disorders". Expert Opinion on Pharmacotherapy (Informa UK Limited) 20 (3): 251–260. February 2019. doi:10.1080/14656566.2018.1549542. PMID 30475091. 
  15. ↑ "New Medicines Newsletter". https://www.sps.nhs.uk/wp-content/uploads/2018/01/New-Medicines-Newsletter-December-2017.pdf. 
  16. ↑ "Efficacy and tolerability of vilazodone for the acute treatment of generalized anxiety disorder: A meta-analysis". Asian Journal of Psychiatry 26: 115–122. April 2017. doi:10.1016/j.ajp.2017.01.016. PMID 28483071. 
  17. ↑ "SUPPLEMENT APPROVAL". U.S. Food and Drug Administration (FDA). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/022567Orig1s019ltr.pdf. 
  18. ↑ "FDA approves Clinical Data Inc's antidepressant". Reuters. January 22, 2011. https://www.reuters.com/article/idUSN2111362920110122. 
  19. ↑ 19.0 19.1 Australian Medicines Handbook 2013. The Australian Medicines Handbook Unit Trust; 2013.
  20. ↑ Taylor D, Paton C, Kapur S, Taylor D. The Maudsley prescribing guidelines in psychiatry. 11th ed. Chichester, West Sussex: John Wiley & Sons; 2012.
  21. ↑ Wang Y-P, Chen Y-T, Tsai C-F, Li S-Y, Luo J-C, Wang S-J, et al. Short-Term Use of Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Bleeding. Am J Psychiatry [Internet]. 2013 Sep 13 [cited 2013 Oct 6]; Available from: http://ajp.psychiatryonline.org/article.aspx?articleid=1738031
  22. ↑ "Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis". JAMA Psychiatry 70 (4): 436–443. April 2013. doi:10.1001/jamapsychiatry.2013.684. PMID 23446732. 
  23. ↑ "Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis". Journal of Perinatology 25 (9): 595–604. September 2005. doi:10.1038/sj.jp.7211352. PMID 16015372. 
  24. ↑ "Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study". BMJ 339 (sep23 1): b3569. September 2009. doi:10.1136/bmj.b3569. PMID 19776103. 
  25. ↑ "Antidepressant use in pregnancy and the risk of cardiac defects". The New England Journal of Medicine 370 (25): 2397–2407. June 2014. doi:10.1056/NEJMoa1312828. PMID 24941178. 
  26. ↑ 26.0 26.1 "Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone". European Journal of Pharmacology 510 (1–2): 49–57. March 2005. doi:10.1016/j.ejphar.2005.01.018. PMID 15740724. 
  27. ↑ "Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist". The Journal of Pharmacology and Experimental Therapeutics 302 (3): 1220–1227. September 2002. doi:10.1124/jpet.102.034280. PMID 12183683. 
  28. ↑ "The discovery and development of vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?". Expert Opinion on Drug Discovery 8 (12): 1529–1539. December 2013. doi:10.1517/17460441.2013.855195. PMID 24195711. 
  29. ↑ "Vilazodone: a 5-HT1A receptor agonist/serotonin transporter inhibitor for the treatment of affective disorders". CNS Neuroscience & Therapeutics 15 (2): 107–117. 2009. doi:10.1111/j.1755-5949.2008.00067.x. PMID 19499624. 
  30. ↑ "Vilazodone: a novel antidepressant". American Journal of Health-System Pharmacy 69 (18): 1551–1557. September 2012. doi:10.2146/ajhp110374. PMID 22935937. 
  31. ↑ "Vilazodone HCl (Viibryd): A Serotonin Partial Agonist and Reuptake Inhibitor For the Treatment of Major Depressive Disorder". P & T 37 (1): 28–31. January 2012. PMID 22346333. 
  32. ↑ "Xconomy: Blend Therapeutics Taps Former Clinical Data Chief Fromkin As New CEO". 13 April 2015. http://www.xconomy.com/boston/2015/04/13/blend-therapeutics-taps-former-clinical-data-chief-fromkin-as-new-ceo/. 



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