informative: Clinical study results

Viibryd efficacy demonstrated through multiple studies in adults with MDD

Primary endpoint at week 81

Significant improvement in MADRS total score vs placebo at primary endpoint (P≤0.01)

MADRS total scores at baseline: 30.8 for VIIBRYD and 30.7 for placebo
42% IMPROVEMENT
from baseline vs 31% for placebo1

LS mean difference (95% confidence interval) from placebo in change from baseline in MADRS total score was -3.2 (-5.2, -1.3) at week 8. Last observation carried forward (LOCF) analysis shown.2

§P=0.001 vs placebo.

  • Whether the statistically significant differences observed at time points earlier than 8 weeks represent clinically relevant treatment effects in this study is unknown

Randomized, double-blind, placebo-controlled, multicenter study to determine the efficacy and safety of VIIBRYD in adults aged 18-65 years who were diagnosed with MDD. Primary endpoint was the change in MADRS total score from baseline to week 8 in the intent-to-treat (ITT) population (LOCF analysis). Mixed-effects model repeated-measure (MMRM) analysis is shown for change by treatment week.

VIIBRYD treatment was initiated once daily at 10 mg for 7 days, followed by 20 mg for another 7 days, and 40 mg thereafter until the end of week 8. VIIBRYD was administered with food.1,2

*Least squares.

Primary endpoint at week 83

Significant improvement in MADRS total score vs placebo at primary endpoint (P≤0.01)

MADRS total scores at baseline: 31.9 for VIIBRYD and 32.0 for placebo
42% IMPROVEMENT
from baseline vs 34% for placebo3

LS mean difference (95% confidence interval) from placebo in change from baseline in MADRS total score was -2.5 (-4.4, -0.6) at week 8. LOCF analysis shown.2

P=0.009 vs placebo.

  • Whether the statistically significant differences observed at time points earlier than 8 weeks represent clinically relevant treatment effects in this study is unknown

Randomized, double-blind, placebo-controlled, multicenter study to determine the efficacy and safety of VIIBRYD in adults aged 18-70 years who were diagnosed with MDD. Primary endpoint was the change in MADRS total score from baseline to week 8 in the intent-to-treat (ITT) population (LOCF analysis). Mixed-effects model repeated-measure (MMRM) analysis is shown for change by treatment week.

VIIBRYD treatment was initiated once daily at 10 mg for 7 days, followed by 20 mg for another 7 days, and 40 mg thereafter until the end of week 8. VIIBRYD was administered with food.2,3

Primary endpoint at week 84

Significant improvement in MADRS total score vs placebo at primary endpoint (P≤0.01)

MADRS total scores at baseline: 30.7 for VIIBRYD and 30.9 for placebo
52% IMPROVEMENT
from baseline vs 36% for placebo2

LS mean difference (95% confidence interval) from placebo in change from baseline in MADRS total total score was -5.1 (-6.9, -3.3) at week 8. MMRM analysis shown.2

P=0.00001 vs placebo.

  • Whether the statistically significant differences observed at time points earlier than 8 weeks represent clinically relevant treatment effects in this study is unknown

Randomized, double-blind, placebo-controlled, multicenter studies to determine the efficacy and safety of VIIBRYD in adults aged 18-70 years who were diagnosed with MDD. Primary endpoint was the change in MADRS total score from baseline to week 8 in the ITT population (MMRM analysis). MMRM analysis is shown for change by treatment week.

VIIBRYD treatment was initiated once daily at 10 mg for 7 days, followed by 20 mg for another 7 days, and 40 mg thereafter until the end of week 8. VIIBRYD was administered with food.4

Primary endpoint at week 105*

Significant improvement in MADRS total score vs placebo at primary endpoint (P≤0.01)

Baseline values: 31.3 for VIIBRYD 20 mg, 31.2 for VIIBRYD 40 mg, and 31.4 for placebo
VIIBRYD 20 mg/day:
55% IMPROVEMENT from baseline vs 47% for placebo2
VIIBRYD 40 mg/day:
56% IMPROVEMENT from baseline vs 47% for placebo2

LS mean difference (95% CI) from placebo in change from baseline in MADRS total score was -2.6 (-4.3, -0.8) for the 20 mg dose and -2.8 (-4.6, -1.1) for the 40 mg dose at week 10. MMRM analysis shown.2

P<0.01 vs placebo.

  • Whether the statistically significant differences observed at time points earlier than 10 weeks represent clinically relevant treatment effects in this study is unknown

Randomized, double-blind, placebo-controlled, multicenter study to determine the efficacy and safety of VIIBRYD in adults aged 18-70 years who were diagnosed with MDD. Primary endpoint was the change in MADRS total score from baseline to week 10 in the ITT population. MMRM analysis is shown for change by treatment week. All patients received 10 mg/day for the first 7 days and then 20 mg/day on days 8-14. Patients in the 20 mg/day group remained on this dose until week 10. Patients in the 40 mg/day group received this dose from day 15 onward until week 10. VIIBRYD was administered with food.2,5

*Statistical significance shown is for VIIBRYD 20 mg/day vs placebo and VIIBRYD 40 mg/day vs placebo. This trial was not powered to demonstrate statistical significance between VIIBRYD 20 mg/day and VIIBRYD 40 mg/day.5

Viibryd should be taken with food2

  • Taking Viibryd on an empty stomach can reduce plasma concentrations (AUC) by approximately 50% and may diminish effectiveness
Indication and Usage

VIIBRYD (vilazodone HCI) is indicated for the treatment of major depressive disorder (MDD) in adults.

Important Safety Information

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term studies. Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors.

The safety and efficacy of VIIBRYD have not been established in pediatric patients.

Contraindications

  • VIIBRYD is contraindicated in patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome.

Warnings and Precautions

  • Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment and when changing the dose. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing VIIBRYD, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
  • Serotonin Syndrome: SNRIs and SSRIs, including VIIBRYD, can cause a potentially life-threatening condition called serotonin syndrome when taken alone, but especially when used concomitantly with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, ie, MAOIs. Symptoms of serotonin syndrome were noted in 0.1% of VIIBRYD-treated patients in premarketing clinical trials. Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms. Monitor all patients taking VIIBRYD for the emergence of serotonin syndrome. If symptoms occur, discontinue VIIBRYD and any concomitant serotonergic agents immediately and initiate supportive treatment. If concomitant use of VIIBRYD with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome.
  • Drugs that interfere with serotonin reuptake inhibition, including VIIBRYD, increase the risk of bleeding events. Inform patients about the risk of bleeding associated with the concomitant use of VIIBRYD and aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing VIIBRYD.
  • Before initiating VIIBRYD, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. Treating a depressive episode with VIIBRYD or another antidepressant in a patient with bipolar disorder may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania/hypomania were noted in 0.1% of undiagnosed patients treated with VIIBRYD. VIIBRYD is not approved for use in treating bipolar depression.
  • Adverse reactions may occur upon discontinuation of serotonergic antidepressants such as VIIBRYD, particularly after abrupt discontinuation. Gradual dose reduction is recommended, instead of abrupt cessation, whenever possible.
  • VIIBRYD should be prescribed with caution in patients with a seizure disorder.
  • The pupillary dilation that occurs following use of many antidepressants, including VIIBRYD, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of VIIBRYD in patients with untreated anatomically narrow angles.
  • Hyponatremia may occur from treatment with SNRIs and SSRIs, including VIIBRYD. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia while taking VIIBRYD. In patients with symptomatic hyponatremia, discontinue VIIBRYD and institute appropriate medical intervention.

Adverse Reactions

  • The most commonly observed adverse reactions with VIIBRYD in 8- to 10-week placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) by dose (20 mg, 40 mg) vs placebo were: diarrhea (26%, 29% vs 10%), nausea (22%, 24% vs 7%), insomnia (7%, 6% vs 2%), and vomiting (4%, 5% vs 2%).

Please also see the full Prescribing Information.

Important Safety Information

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term studies. Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors.

The safety and efficacy of VIIBRYD have not been established in pediatric patients.

Contraindications

  • VIIBRYD is contraindicated in patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome.

Warnings and Precautions

  • Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment and when changing the dose. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing VIIBRYD, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
  • Serotonin Syndrome: SNRIs and SSRIs, including VIIBRYD, can cause a potentially life-threatening condition called serotonin syndrome when taken alone, but especially when used concomitantly with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, ie, MAOIs. Symptoms of serotonin syndrome were noted in 0.1% of VIIBRYD-treated patients in premarketing clinical trials. Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms. Monitor all patients taking VIIBRYD for the emergence of serotonin syndrome. If symptoms occur, discontinue VIIBRYD and any concomitant serotonergic agents immediately and initiate supportive treatment. If concomitant use of VIIBRYD with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome.
  • Drugs that interfere with serotonin reuptake inhibition, including VIIBRYD, increase the risk of bleeding events. Inform patients about the risk of bleeding associated with the concomitant use of VIIBRYD and aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing VIIBRYD.
  • Before initiating VIIBRYD, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. Treating a depressive episode with VIIBRYD or another antidepressant in a patient with bipolar disorder may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania/hypomania were noted in 0.1% of undiagnosed patients treated with VIIBRYD. VIIBRYD is not approved for use in treating bipolar depression.
  • Adverse reactions may occur upon discontinuation of serotonergic antidepressants such as VIIBRYD, particularly after abrupt discontinuation. Gradual dose reduction is recommended, instead of abrupt cessation, whenever possible.
  • VIIBRYD should be prescribed with caution in patients with a seizure disorder.
  • The pupillary dilation that occurs following use of many antidepressants, including VIIBRYD, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of VIIBRYD in patients with untreated anatomically narrow angles.
  • Hyponatremia may occur from treatment with SNRIs and SSRIs, including VIIBRYD. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia while taking VIIBRYD. In patients with symptomatic hyponatremia, discontinue VIIBRYD and institute appropriate medical intervention.

Adverse Reactions

  • The most commonly observed adverse reactions with VIIBRYD in 8- to 10-week placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) by dose (20 mg, 40 mg) vs placebo were: diarrhea (26%, 29% vs 10%), nausea (22%, 24% vs 7%), insomnia (7%, 6% vs 2%), and vomiting (4%, 5% vs 2%).

Please also see the full Prescribing Information.