How is vilazodone different from other SSRIs? A unique mechanistic approach is that of vilazodone, an agent that combines two mechanisms in a single drug, namely that of the SSRIs with 5HT1A receptor partial agonist actions, or a serotonin partial agonist reuptake inhibitor (SPARI).

1. VILAZODONE
Presenter: Dr. Dikshya Upreti
PG Resident
Department of Psychiatry
NMCTH,Birgunj

2. Classification of antidepressant
1. Cyclic antidepressants
2. Selective serotonin reuptake inhibitors (SSRIs)
3. Serotonin partial agonist/reuptake inhibitors (SPARIs)
4. Norepinephrine–dopamine reuptake inhibitors (NDRIs)
5. Selective norepinephrine reuptake inhibitors(SNRIs)
6. Norepinephrine serotonin reuptake Enhancers (NSREs)
7. Noradrenergic and specific serotonergic antagonists (NaSSAs)
8. Serotonin antagonists and reuptake inhibitors(SARIs)
9. Noradrenergic reuptake inhibitors(NARIs)
10. Mono-amine oxidase inhibitors(MAOIs)
11. Melatonin receptor agonist and 5-HT2c antagonist
Stahl’s Essential Psychopharmacology, 4th editio

3. Serotonin partial agonist/reuptake
inhibitors (SPARIs)
■ A new antidepressant introduced in the US is vilazodone, which
combines SERT inhibition with a second property: 5HT1A partial
agonism.
■ The combination of serotonin reuptake inhibition with 5HT1A partial
agonism has long been known by clinicians to enhance the
antidepressant properties and tolerability of SSRIs/SNRIs in some
patients.
■ Although vilazodone is the only approved agent selective for just these
two actions.
Stahl’s Essential Psychopharmacology, 4th
edition

4. Mechanism of action of serotonin partial
agonist/reuptake inhibitors (SPARIs)
When a SPARI is administered, about half of serotonin
transporters (SERTs) and half of serotonin 1A (5HT1A)
receptors are occupied immediately.
Blockade of the serotonin transporter (SERT) causes
serotonin to increase initially in the somatodendritic
area of the serotonin neuron.

5. The consequence of serotonin increasing in the
somatodendritic area, is that the somatodendritic 5HT1A
autoreceptors desensitize or downregulate.
Once the somatodendritic receptors downregulate,
there is no longer inhibition of impulse flow in the
serotonin (5HT) neuron. Thus, neuronal impulse flow
is turned on. The consequence of this is release of

6. ■ Approved by the FDA for use in the United States to treat major
depressive disorder in Adults in 2011.
■ 5HT1A partial agonist actions plus SERT inhibition can also be
attained by augmenting SSRIs/SNRIs with the 5HT1A partial
agonist buspirone.

7. Vilazodone Buspirone
5HT1A partial agonists occupy more
5HT1A receptors for longer time
Weaker 5HT1A partial agonists occupy
fewer 5HT1A receptors for a shorter
time
Vilazodone binds to 5HT1A receptors
with higher affinity than 5HT
Buspirone and 6-hydroxybuspirone also
bind to 5HT1A receptors with lower
affinity than 5HT itself
Vilazodone is dosed so that about 50%
of both SERTS and 5HT1A receptors are
occupied.
Buspirone augments an SSRI, the
buspirone is generally dosed so that
about 10–20% of 5HT1A receptors are
occupied and the SSRI is dosed so that
about 80% of SERTS are blocked.
It could account for the apparent lesser
incidence of sexual dysfunction.
It could account for the apparent more
incidence of sexual dysfunction.
Stahl’s Essential Psychopharmacology, 4th edition

8. Pharmacodynamics and
pharmacokinetics
1. Onset of action: Depression:
Initial effects may be observed within 1 to 2 weeks of
treatment, with continued improvements through 4 to 6
weeks.
2. Protein binding: ~96% to 99%
3. Metabolism: Extensively hepatic, via CYP3A4 (major
pathway) and 2C19 and 2D6 (minor pathways)
4. Bioavailability: 72% (with food); blood concentrations (AUC)
may be decreased ~50% in the fasted state
5. Half-life elimination: Terminal: ~25 hours
6. Time to peak serum: 4 to 5 hours
7. Excretion: Urine (1% as unchanged drug)
Feces (2% as unchanged drug)

9. Indication
■ Major depressive disorder, unipolar (alternative agent)
Oral:
Initial: 10 mg once daily for 7 days, then increase to 20 mg once daily;
may increase up to 40 mg once daily after an additional ≥7 days based
on response and tolerability (maximum dose: 40 mg/day).

10. ■ Discontinuation of therapy:
The half-life of vilazodone is approximately 24 hours, decreasing
the likelihood of withdrawal symptoms compared to drugs with half-
lives significantly less than 24 hours

11. Dose adjustment:
■ Dosing: Renal Impairment: Adult: No dosage adjustment
necessary.
■ Dosing: Hepatic Impairment: Adult: No dosage adjustment
necessary.
■ Dosing: Geriatric Refer to adult dosing.
Geriatric patients: High-risk medication: Beers Criteria: Selective
Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers
Criteria as potentially inappropriate medications to be used with
caution in patients 65 years and older due to the potential to cause
or exacerbate syndrome of inappropriate antidiuretic hormone
secretion (SIADH) or hyponatremia; monitor sodium concentration
closely when initiating or adjusting the dose in older adults.
American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate
Medication Use in Older Adults. Journal of the American Geriatrics Society, 67(4), 674–694.

12. Drug Interactions
■ Acalabrutinib: May enhance the antiplatelet effect of Agents with
Antiplatelet properties.
■ Alcohol
■ Agents with blood glucose lowering effects: selective serotonin
reuptake inhibitors may enhance the hypoglycemic effect of agents
with blood glucose lowering effects.
■ Amphetamines
■ Anticoagulants
■ Antiemetics (5HT3 antagonists)
■ Aspirin
■ Buspirone

13. Adverse Reactions
>10%:
■ Central nervous system: Headache Gastrointestinal: Diarrhea, nausea
1% to 10%:
■ Cardiovascular: Palpitations
■ Central nervous system: Dizziness , insomnia , drowsiness, fatigue, abnormal
dreams, restlessness, paresthesia, delayed ejaculation, migraine, sedation,
panic attack, ventricular premature contractions
■ Dermatologic: Hyperhidrosis. night sweats
■ Endocrine & metabolic: Decreased libido, weight gain
■ Gastrointestinal: Xerostomia , abdominal pain, vomiting, dyspepsia,
flatulence, increased appetite, abdominal distension, gastroenteritis
■ Genitourinary: Erectile dysfunction, orgasm disturbance
■ Neuromuscular & skeletal: arthralgia , tremor
■ Ophthalmic: Blurred vision, xerophthalmia
Hyperhidrosis

14. Contraindications
■ Use of MAO inhibitors (concurrently or within 14 days of
discontinuing either vilazodone or the MAO inhibitor), including
MAO inhibitors such as linezolid or intravenous methylene blue

15. Warnings/Precautions major psychiatric
warnings:
■ Suicidal thinking/behavior: [US Boxed Warning]: Increased the
risk in pediatric and young adult patients
■ Vilazodone is not approved for use in pediatric patients.
■ Vilazodone is not FDA approved for the treatment of bipolar
depression.
■ Seizure disorder:
Use with caution in patients with a previous seizure disorder or
condition predisposing to seizures such as brain damage or
alcoholism.
■ Discontinuation syndrome

16. Pregnancy and Breast-Feeding
■ Category C
■ Information related to the use of vilazodone in pregnancy is limited
■ If treatment for major depressive disorder is initiated for the first
time during pregnancy, vilazodone is not one of the preferred agents
(CANMAT [MacQueen 2016];
■ Patients treated for major depression and who are euthymic prior to
pregnancy are more likely to experience a relapse when medication is
discontinued (68%) as compared to pregnant patients who continue
taking antidepressant medications (26%) (Cohen 2006).
■ It is not known if vilazodone is present in breast milk.
■ Information related to the postpartum use of vilazodone is limited

17. Reproductive Considerations
■ If treatment for major depressive disorder is initiated for the first
time in patients planning to become pregnant, vilazodone is not a
preferred antidepressant
■ Vilazodone may be associated with male and female treatment-
emergent sexual dysfunction.
■ Decreased libido and abnormal orgasm/anorgasmia have been
reported in females; ejaculation disorder, decreased libido, and
erectile dysfunction have been reported in males with vilazodone
use.

18. Pricing:
■ USKit (Viibryd Starter Pack Oral)
10 & 20 mg (per each): $12.01
■ Tablets (Viibryd Oral)
1. 10 mg (per each): $12.01
2. 20 mg (per each): $12.01
3. 40 mg (per each): $12.01
Product Company Price (Rs.) (Nepalese)
Valz 40 mg Tablet 10s Torrent Pharma 219.00
Vilarest 40 mg Tablet 10s CIPLA 230.00
Vilamid 40mg Tablet 10s LUPIN 258.00
Vilano 40mg Tablet 10s Sun Pharma 335.00

19. ■ Sexual side effects sexual dysfunction occurred with sertraline
and Escitalopram but not with vilazodone; instead, there was an
improvement on the ASEX scale of sexual function.
■ Weight gain there was weight gain in patients who were taking
sertraline and Escitalopram, whereas there was no weight gain
in the patients who were prescribed vilazodone.
Bathla, M., & Anjum, S. (2020). A 12-week prospective randomized controlled
comparative trial of vilazodone and sertraline in Indian patients with
depression. Indian journal of pharmacology, 52(1), 10–15.
Bathla, M., Anjum, S., Singh, M., Panchal, S., & Singh, G. P. (2018). A 12-week
Comparative Prospective Open-label Randomized Controlled Study in Depression Patients
Treated with Vilazodone and Escitalopram in a Tertiary Care Hospital in North
India. Indian journal of psychological medicine, 40(1), 80–85.

20. Categorical improvements in disease severity in patients with major
depressive disorder treated with vilazodone
Durgam, S., Chen, C., Gommoll, C. P., Edwards, J., & Citrome, L. (2016). Categorical improvements in
disease severity in patients with major depressive disorder treated with vilazodone: post hoc analysis of
four randomized, placebo-controlled trials. Neuropsychiatric disease and treatment, 12, 3073–3081.

21. Sexual function in patient taking Vilazodone
Clayton, A. H., Durgam, S., Tang, X., Chen, C., Ruth, A., & Gommoll, C. (2016). Characterizing sexual
function in patients with generalized anxiety disorder: a pooled analysis of three vilazodone
studies. Neuropsychiatric disease and treatment, 12, 1467–1476.

22. Comparative evaluation of efficacy and tolerability of vilazodone,
escitalopram, and amitriptyline
Renuka L. Kadam,et,al,

23. References:
■ American Psychiatric Association (APA). Practice guideline for the
treatment of patients with major depressive disorder. 3rd ed.
■ (CANMAT [MacQueen 2016];
■ (Cohen 2006).
■ Stahl’s Essential Psychopharmacology, 4th edition
■ Bathla, M., & Anjum, S. (2020).
■ Bathla, M., Anjum, et.al (2018)
■ Durgam, S,et.al (2016)
■ Renuka L. Kadam,et,al, 2020
■ 2019 Updated AGS Beers Criteria
■ Clayton, A. H.,et.al(2016)
■ UpToDate