Vilazodone is a serotonin partial agonist and reuptake inhibitor (SPARI) antidepressant approved for treatment of major depressive disorder. It has a dual mechanism of action - selective serotonin reuptake inhibition and high-affinity partial agonism of serotonin 5-HT1A receptors. This dual action provides faster onset of antidepressant effects within 1-2 weeks. Studies have shown vilazodone to be effective and well-tolerated for short-term and long-term treatment of MDD, with comparable efficacy to SSRIs like escitalopram. It has fewer sexual side effects than SSRIs. The recommended dosage range is 40 mg per day.

1. Dr. Subodh Sharma
Resident, MD, Psychiatry
Department of Psychiatry
NMCTH, Birgunj, Nepal

2.  Serotonin modulator
 FDA approved in 2011 for use in Major Depressive Disorder
 Approved in India in 2015
 Developed by Merck Pharmaceuticals
 Aka Serotonin Partial Agonist and Reuptake Inhibitor
(SPARI)

3. » Selective inhibition of serotonin reuptake
•Facilitates function of Serotonin
» High-affinity 5-HT1A receptor partial agonist
•Functions itself as Serotonin
» Favourable interplay with the HPA axis and
5-HT1A
•Role in Corticosteroid Secretion from Hippocampus and Amygdala

5.  Due to its dual action leads to faster action (As soon as one week)
 Serotonin Partial Agonistic function is also shown by Buspirone , Aripiprazole and
other Antipsychotics which are used as augmentation.
 But Vilazodone is superior in its affinity and added Serotonin reuptake inhibition.
 Less sexual side-effects; no action in NE mechanism.

6.  The short-term efficacy of vilazodone for the treatment of MDD in adults has been
assessed in two pivotal, 8-week, randomized, double-blind, placebo-controlled,
parallel-group, multicenter trials, namely study 04 (n=205 vs 204) and study
07(n=233 vs 235) using HAM-D17 and MADRS.
 Both Studies were done using 40mg of Vilazodone.
 Frampton, J. E. (2011). Vilazodone. CNS Drugs, 25(7), 615–627.
 Study 04: Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and
tolerability of vilazodone in the treatment of major depressive disorder: a randomized,
double-blind, placebo-controlled trial. J Clin Psychiatry 2009 Mar; 70 (3): 326-33 39.
 Study 07: Khan A, Cutler AJ, Kajdasz DK, et al. A randomized, double-blind, placebo-
controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major
depressive disorder. J Clin Psychiatry 2011; 72

7.  Longterm efficacy : Long-term (52 weeks’) treatment with vilazodone 40 mg once
daily was associated with an improvement in depressive symptoms, as evidenced
by decreases over time in the mean MADRS total score (from 29.9 at baseline to
7.1 at week 52). (n=599)
 Robinson D, Kajdasz D, Gallipoli S, et al. A 1-year openlabel study assessing the safety
and tolerability of vilazodone in patients with major depressive disorder
 Another study 2018 ; network metanalysis comprising 522 trials, 116477
participants compared 21 antidepressants showed that Vilazodone was superior to
citalopram, fluoxetine, desvenlafaxine, Similar efficacy with escitalopram,
sertraline, but inferior to venlafaxine, paroxetine and amitryptiline.
 A. Ciprani et al. “Comparative efficacy and acceptability of 21 antidepressant drugs for the acute
treatment of adults with major depressive disorder; a systematic review and network meta-
analysis.”

8.  A recent 2021 study in India comparing Vilazodone,
escitalopram and placebo using MADRS stated that;
 “Vilazodone demonstrated comparable efficacy to
escitalopram and superior efficacy over the placebo in
the treatment of MDD.”
 Sinha, Shubhadeep et al. “A Phase III Prospective Active and
Placebo-Controlled Randomized Trial of Vilazodone in the
Treatment of Major Depressive Disorder.” Cureus vol. 13,7
e16689. 28 Jul. 2021, doi:10.7759/cureus.16689

9.  Another Study in India in 2020 comparing
Vilazodone, Escitalopram and Amitriptyline
using HAM-D17 and MADRS (n=17/16/17)
stated that:
 “Vilazodone is more efficacious and well
tolerated antidepressant compared to
escitalopram and amitriptyline.”
 Kadam, Renuka L et al. “Comparative evaluation
of efficacy and tolerability of vilazodone,
escitalopram, and amitriptyline in patients of major
depressive disorder: A randomized, parallel, open-
label clinical study.” Indian journal of
pharmacology vol. 52,2 (2020): 79-85.
doi:10.4103/ijp.IJP_441_18

10.  Another study comparing popular SSRIs
with Vilazodone showed comparative
efficacy but with significant decline in
MADRS score in week 1.
 Shweta Chauhan et al.: Is Vilazodone Really
the Answer to the Delay Associated with the
Onset of Antidepressant Action of SSRIs? – A
Randomised Control Trial

11.  In the meta-analysis, treatment-emergent sexual dysfunction in the active SSRI
groups ranged from 25.8% (fluvoxamine) to 80.3% (sertraline)
 The rates of treatment-emergent sexual dysfunction observed among patients who
were functional at baseline in the vilazodone groups are relatively low and closer
to that of placebo than the rates reported for most SSRIs (citalopram,
escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline).
 Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants:
A meta-analysis. J Clin Psychopharmacology 2009;29:259–66.

12.  GI Upset (Nausea, Vomitting and Diarrohea )with headache are commonest side
effects. (>10%)
 Other Side effects include:
 Dizziness
 Dryness
 Insomnia
 Tremors
 Palpitations
 Rarely seizures

13. • Usual Dosage Range • 40 mg/day
• Dosage Forms • Tablets 10 mg, 20 mg, 40 mg
• Recommended titration schedule • Initial 10 mg/day; increase to 20 mg/day after
one week; increase to 40 mg/day after one more week; should be taken with food
• Dosing Tips – Given once daily, any time of day tolerated but must be
administered with food, because taking on an empty stomach may reduce
absorption of vilazodone by 50%
• If intolerable anxiety, insomnia, agitation, akathisia, or activation occur either
upon dosing initiation or discontinuation, consider the possibility of activating a
bipolar disorder and switch to a mood stabilizer or an atypical antipsychotic
• Dosage higher than 40 mg may be effective in some patients, particularly those
with treatment-resistant depression who fail to respond adequately to 40 mg daily

14.  71 patients were abruptly switched from ineffective SSRI or SNRI medications to
vilazodone 10, 20, or 40 mg/day.
 significant reduction in mean ± standard error of mean in MADRS score from
baseline ( 26.81) to week 8 (9.86 ) in the three groups combined (P<0.001)
 there were no significant differences between the three vilazodone dose-initiation
groups in mean changes in MADRS or HAMA scores
 ASEX scores showed a decrease from baseline (17.5 ) to end point (15.9 ) (p=0.01)
among patients switched from SSRI and SNRI medications to vilazodone.
 Patkar A, Rele S, Millet M, et al. A 8-week randomized, double-blind trial comparing efficacy,
safety and tolerability of three vilazodone dose initiation strategies following switch from SSRIs
or SNRIs in major depressive disorder. 2014.

15.  Recommended as a first line treatment as its combined SPARI mechanism offers a
unique initial antidepressant approach when compared to SSRI, SNRI, etc.
 Likely be used in those who do not respond to a SSRI/SNRI or donot tolerate a
SSRI/ SNRI given their prevalence and ease of use as well as potential for faster
titration and lower gastrointestinal side effect profiles.
 Especially useful if the patient develops sexual dysfunction, weight gain or
increased BP on SSRI/SNRI.
 Should strongly be considered, if patients cannot tolerate or risk intervention with
an atypical second generation Antipsychotic Augmentation Trial due to weight
gain, sedation, extrapyramidal symptoms, or dyslipidemia.
 Stahl S. Essential Psychopharmacology: The Prescriber’s Guide. Cambridge, UK: Cambridge University Press;
2011.
 Stahl S. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge, UK:
Cambridge University Press; 2008.

16.  Bioavailability : 72% with food
 Peak plasma time : 4-5 hrs
 Distribution: protein bound 96-99%
 Metabolism: CYP pathway and Carboxylesterase pathways
 Half Life: 25 hrs

17.  Contraindicated in Hypersensitivity and drugs like selegiline, rasagiline
 Significant interaction with : amitryptiline, buspirone, citalopram, cocaine,
duloxetine, escitalopram, Fluoxetine, Imipramine, isoniazide, lithium,
mirtazapine, nortryptiline
 No dose adjustment required for hepatic or renal impairment
 No controlled study in pregnancy so consider risk vs benefit
 (1 case study showed no significant effect in baby born with mother under 40mg
vilazodone) ( Morrison CM. A case report of the use of vilazodone in pregnancy. Prim Care Companion CNS Disord.
2013;16(2).)
 Found to be secreted in milk in animal studies, no study in humans.

18.  Not available in Nepal.
 Widely practiced in India
 Available brands in India:
 VILAZINE (Intas) 20/40mg
 INR 324/40mg x 10tablets
 VALZ (Torrent) 20/40mg
 INR 349/40mg x 10 tablets
 Escitalopram Cost
 Rexipra 10mg (INR 8/ tablet)
 Feliz 10mg (INR 6/tablet)

19.  Faster action with comparable efficacy with popular antideppresants
 Low sexual side-effects which one of the most common reasons for discontinuing
other antidepressant medications.
 Higher cost and unavailability.
 Can be considered as Second Line antidepressant in our setting in affording
population.

20.  Stahl’s Essentials of Psychopharmacology, Fourth Edition, SM Stahl
 Morrison CM. A case report of the use of vilazodone in pregnancy. Prim Care Companion CNS Disord.
2013;16(2)
 Frampton, J. E. (2011). Vilazodone. CNS Drugs, 25(7), 615–627.
 Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and tolerability of vilazodone in the
treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin
Psychiatry
 Khan A, Cutler AJ, Kajdasz DK, et al. A randomized, double-blind, placebo-controlled, 8-week study of
vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry
Robinson D, Kajdasz D, Gallipoli S, et al. A 1-year openlabel study assessing the safety and tolerability of
vilazodone in patients with major depressive disorder
 Sinha, Shubhadeep et al. “A Phase III Prospective Active and Placebo-Controlled Randomized Trial of
Vilazodone in the Treatment of Major Depressive Disorder.” Cureus vol. 13,7
 Patkar A, Rele S, Millet M, et al. A 8-week randomized, double-blind trial comparing efficacy, safety and
tolerability of three vilazodone dose initiation strategies following switch from SSRIs or SNRIs in major
depressive disorder. 2014.
 Kadam, Renuka L et al. “Comparative evaluation of efficacy and tolerability of vilazodone, escitalopram,
and amitriptyline in patients of major depressive disorder: A randomized, parallel, open-label clinical
study.” Indian journal of pharmacology
 Shweta Chauhan et al.: Is Vilazodone Really the Answer to the Delay Associated with the Onset of
Antidepressant Action of SSRIs? – A Randomised Control Trial
 Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: A meta-analysis. J
Clin Psychopharmacology 2009

21. THANK YOU!