Vilazodone (United States trade name Viibryd) is a serotonergic antidepressant developed by Clinical Data for the treatment of major depressive disorder. The chemical compound was originally developed by Merck KGaA (Germany). By 2009 two [2 ] phase III clinical trials with positive results had been completed. Vilazodone was approved by the FDA for use in the United States to treat major depressive disorder on January 21, 2011. [3 ] [4 ] [5 ] [6 ] Medical uses [edit ] Major Depressive Disorder [edit ]
According to two eight-week, randomized, double-blind, placebo-controlled trials in adults, vilazodone was reported to elicit an antidepressant response after one week of treatment. After eight weeks, subjects assigned to vilazodone 40mg daily dose (titrated over 2 weeks) experienced a significantly higher response rate than the group given placebo (44% vs 30%, P = .002). But, remission rates for vilazodone were not significantly different versus placebo.
[7 ] [8 ]
However, FDA staff called these claims into question in a September 2011 article that concluded "it is unknown whether [vilazodone] has any advantages compared to other drugs in the antidepressant class."
[9 ] Adverse Effects [edit ]
After a 1 year, open-label study assessing the safety and tolerability of vilazodone in patients 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. In contrast to other SSRIs currently on the market, initial clinical trials showed that vilazodone did not cause significant [10 ] decreased sexual desire/function as with many other antidepressants, which often cause people to abandon their use. [4 ] Incidence of Adverse Effects [edit ]
[1 ] Very common adverse effects (incidence > 10%) Nausea Diarrhea Sleep Paralysis Common adverse effects (1-10% incidence) Uncommon adverse effects (0.1-1% incidence) Rare adverse effects (<0.1% incidence) -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. [11 ] 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. [11 ] [12 ] [13 ] 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. Overdose [edit ]
Adverse reactions of VIIBRYD at doses of 200-280 mg included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation.
Pharmacology [edit ]
Vilazodone acts as a
serotonin reuptake inhibitor (IC 50 = 2.1 nM; K i = 0.1 nM) and 5-HT 1A receptor partial agonist (IC 50 = 0.2 nM; IA = ~60–70%). [14 ] It has negligible [15 ] affinity for other serotonin receptors such as 5-HT, 1D 5-HT, and 2A 5-HT. 2C [14 ] [15 ]
It also exhibits negligible inhibitory activity at the norepinephrine and dopamine transporters (IC
50 = 56 nM for NET and 37 nM for DAT). [1 ] Partial agonism of the 5-HT is a relatively novel mechanism of action and is also shared by the 1A receptor anxiolytic buspirone (Buspar), the atypical antipsychotics aripiprazole (Abilify) and lurasidone (Latuda) ,and the novel antidepressant vortioxetine (Brintellix). Ingredients [edit ] Viibryd (US) [edit ]
Viibryd is available in
tablet form as the hydrochloride salt of vilazodone. Inactive ingredients include lactose monohydrate, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and various FD&C colorings (Blue #1, Yellow #6, Red #40) depending on the dose. [1 ] See also [edit ] References [edit ] ^ a b c d e f g "VIIBRYD (vilazodone hydrochloride) tablet VIIBRYD (vilazodone hydrochloride) kit [Forest Laboratories, Inc.]". DailyMed. Forest Laboratories, Inc. December 2012 . Retrieved 28 October 2013. ^ August 17th, 2006 Clinical Data's Vilazodone Patient Enrollment Over One Third Complete. ^ de Paulis T (March 2007). "Drug evaluation: Vilazodone--a combined SSRI and 5-HT1A partial agonist for the treatment of depression". IDrugs : the Investigational Drugs Journal 10 (3): 193–201. PMID 17351874. ^ a b "FDA approves Clinical Data Inc's antidepressant". Reuters. January 22, 2011. ^ "FDA approves Clinical Data Inc's antidepressant". Reuters. January 22, 2011. ^ "Clinical Data, Inc. - Clinical Data, Inc. Submits New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder". ^ Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, Reed CR (March 2009). "Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial". The Journal of Clinical Psychiatry 70 (3): 326–33. PMID 19284933. ^ USA (2013-01-30). "A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder". Ncbi.nlm.nih.gov . Retrieved 2013-02-28. ^ Laughren TP, Gobburu J, Temple RJ, Unger EF, Bhattaram A, Dinh PV, Fossom L, Hung HM, Klimek V, Lee JE, Levin RL, Lindberg CY, Mathis M, Rosloff BN, Wang SJ, Wang Y, Yang P, Yu B, Zhang H, Zhang L, Zineh I (September 2011). "Vilazodone: clinical basis for the US Food and Drug Administration's approval of a new antidepressant". The Journal of Clinical Psychiatry 72 (9): 1166–73. doi: 10.4088/JCP.11r06984. PMID 21951984. ^ USA (2013-01-30). "A 1-year, open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder". Ncbi.nlm.nih.gov . Retrieved 2013-02-28. ^ a b Australian Medicines Handbook 2013. The Australian Medicines Handbook Unit Trust; 2013. ^ Taylor D, Paton C, Kapur S, Taylor D. The Maudsley prescribing guidelines in psychiatry. 11th ed. Chichester, West Sussex: John Wiley & Sons; 2012. ^ 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 ^ a b Page ME, Cryan JF, Sullivan A, et al. (September 2002). "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): 1220–7. doi: 10.1124/jpet.102.034280. PMID 12183683. ^ a b Hughes ZA, Starr KR, Langmead CJ, et al. (March 2005). "Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone". European Journal of Pharmacology 510 (1–2): 49–57. doi: 10.1016/j.ejphar.2005.01.018. PMID 15740724.
Agonists: Azapirones: Alnespirone Binospirone Buspirone Enilospirone Eptapirone Gepirone Ipsapirone Perospirone Revospirone Tandospirone Tiospirone Umespirone Zalospirone; Antidepressants: Etoperidone Nefazodone Trazodone Vortioxetine; Antipsychotics: Aripiprazole Asenapine Clozapine Quetiapine Ziprasidone; Ergolines: Dihydroergotamine Bromocriptine Ergotamine Lisuride Methysergide LSD; Tryptamines: 5-CT 5-MeO-DMT 5-MT Bufotenin DMT Indorenate Psilocin Psilocybin; Others: 8-OH-DPAT Adatanserin Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Ebalzotan Eltoprazine F-11,461 F-12,826 F-13,714 F-14,679 F-15,063 F-15,599 Flesinoxan Flibanserin Lesopitron LY-293,284 LY-301,317 MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S 14,506 S-14,671 S-15,535 Sarizotan SSR-181,507 Sunepitron U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine Antagonists: Antipsychotics: Iloperidone Risperidone Sertindole; Beta blockers: Alprenolol Cyanopindolol Iodocyanopindolol Oxprenolol Pindobind Pindolol Propranolol Tertatolol; Others: AV965 BMY-7,378 CSP-2503 Dotarizine Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine/Methiothepin MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100,135 WAY-100,635 Xylamidine Agonists: Lysergamides: Dihydroergotamine Methysergide; Triptans: Almotriptan Avitriptan Eletriptan Frovatriptan Naratriptan Rizatriptan Sumatriptan Zolmitriptan; Tryptamines: 5-CT 5-Ethyl-DMT 5-MT 5-(Nonyloxy)tryptamine; Others: CP-135,807 Bromocriptine CP-286,601 GR-46611 L-694,247 L-772,405 PNU-109,291 PNU-142633 Antagonists: Lysergamides: Metergoline; Others: Alniditan BRL-15,572 Elzasonan GR-127,935 Ketanserin LY-310,762 LY-367,642 LY-456,219 LY-456,220 Metitepine/Methiothepin Ritanserin Yohimbine Ziprasidone
Agonists: Phenethylamines: 2C-B 2C-E 2C-I 2C-T-2 2C-T-7 2C-T-21 DOB DOC DOI DOM MDA MDMA Mescaline; Piperazines: Aripiprazole mCPP TFMPP; Tryptamines: 5-CT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MT α-ET α-Methyl-5-HT α-MT Bufotenin DET DiPT DMT DPT Psilocin Psilocybin; Others: A-372,159 AL-38022A Alstonine Bromocriptine CP-809,101 Dimemebfe Lorcaserin Medifoxamine MK-212 Org 12,962 ORG-37,684 Oxaflozane PHA-57378 PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Vabicaserin WAY-629 WAY-161,503 YM-348 Antagonists: Atypical antipsychotics: Clorotepine Clozapine Iloperidone Melperone Olanzapine Paliperidone Quetiapine Risperidone Sertindole Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine Pimozide Pipamperone; Antidepressants: Agomelatine Amitriptyline Amoxapine Aptazapine Etoperidone Fluoxetine Mianserin Mirtazapine Nefazodone Nortriptyline Tedatioxetine Trazodone; Others: Adatanserin CEPC Cinanserin Cyproheptadine Deramciclane Dotarizine Eltoprazine Esmirtazapine FR-260,010 Ketanserin Ketotifen Latrepirdine Metitepine/Methiothepin Methysergide Pizotifen Ritanserin RS-102,221 S-14,671 SB-200,646 SB-206,553 SB-221,284 SB-228,357 SB-242,084 SB-243,213 SDZ SER-082 Xylamidine
Agonists: Lysergamides: Dihydroergotamine Ergotamine Lisuride LSD Mesulergine Metergoline Methysergide; Tryptamines: 2-Methyl-5-HT 5-BT 5-CT 5-MT Bufotenin E-6801 E-6837 EMD-386,088 EMDT LY-586,713 N-Methyl-5-HT Tryptamine; Others: WAY-181,187 WAY-208,466 Antagonists: Antidepressants: Amitriptyline Amoxapine Clomipramine Doxepin Mianserin Nortriptyline; Atypical antipsychotics: Aripiprazole Asenapine Clorotepine Clozapine Fluperlapine Iloperidone Olanzapine Tiospirone; Typical antipsychotics: Chlorpromazine Loxapine; Others: BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742,457 Ketanserin Latrepirdine Lu AE58054 Metitepine/Methiothepin MS-245 PRX-07034 Ritanserin Ro04-6790 Ro 63-0563 SB-258,585 SB-271,046 SB-357,134 SB-399,885 SB-742,457 Agonists: Lysergamides: LSD; Tryptamines: 5-CT 5-MT Bufotenin; Others: 8-OH-DPAT AS-19 Bifeprunox E-55888 LP-12 LP-44 RU-24,969 Sarizotan Antagonists: Lysergamides: 2-Bromo-LSD Bromocriptine Dihydroergotamine Ergotamine Mesulergine Metergoline Methysergide; Antidepressants: Amitriptyline Amoxapine Clomipramine Imipramine Maprotiline Mianserin; Atypical antipsychotics: Amisulpride Aripiprazole Asenapine Clorotepine Clozapine Olanzapine Risperidone Sertindole Tiospirone Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine; Pimozide; Others: Butaclamol EGIS-12,233 Ketanserin LY-215,840 Metitepine/Methiothepin Ritanserin SB-258,719 SB-258,741 SB-269,970 SB-656,104 SB-656,104-A SB-691,673 SLV-313 SLV-314 Spiperone SSR-181,507 Vortioxetine
Simple piperazines (no additional rings) Phenylpiperazines Acaprazine Antrafenine Aripiprazole Batoprazine Bifeprunox BRL-15,572 Ciprofloxacin CSP-2503 Dapiprazole DCPP DMPP Diphenylpiperazine Dropropizine EGIS-12,233 Elopiprazole Eltoprazine Enpiprazole Ensaculin Etoperidone Flesinoxan Flibanserin Fluprazine Itraconazole Ketoconazole Levodropropizine Lorpiprazole mCPP Mefway MeOPP Mepiprazole Naftopidil Naluzotan Naphthylpiperazine Nefazodone Niaprazine Oxypertine Pardoprunox pCPP pFPP Posaconazole S-14,506 S-14,671 S-15,535 SB-258,585 SB-271,046 SB-357,134 SB-399,885 Sonepiprazole TFMPP Tolpiprazole Trazodone Urapidil Vesnarinone Vilazodone Vortioxetine WAY-100,135 WAY-100,635 Benzylpiperazines Diphenylalkylpiperazines (benzhydrylalkylpiperazines) Pyrimidinylpiperazines Pyridinylpiperazines Benzo(iso)thiazolyl piperazines Tricyclics (piperazine attached via side chain) Others/Uncategorized