国立保健医療科学院 保健医療経済評価研究センター
Center for Outcomes Research and Economic
Evaluation for Health (C2H), National Institute of
Public Health (NIPH) | URL: http://c2h.niph.go.jp

June 1st, 2021

[C2H1905] Summary of cost-effectiveness evaluationof Vortioxetine (Trintellix)

1. Indications
Depression and depressive symptoms
2. Price of drug
Vortioxetine was reimbursed from November 2019 onward for JPY 168.90 (10 mg)
and JPY 253.40 (20 mg) as of May 2021. The price was calculated using a similar
efficacy comparison method, with a usefulness premium of 5%. This product wasdesignated as an H1 cost-effectiveness evaluation item.
3. Scope of cost-effectiveness evaluation
This product is a serotonin reuptake inhibitor/serotonin receptor agonist andantagonist that has indications for depression and depressive symptoms. The scopeof evaluation agreed upon at the first session of the Expert Committee of CostEffectiveness Evaluation (ECCEE) is described hereafter. The target population wasdivided into (a) mild depression and depressive symptoms and (b) moderate andsevere depression and depressive symptoms. According to clinical guidelines,
antidepressants are not recommended as the main therapy for patients with milddepression. In contrast, new antidepressants including selective serotonin reuptake
inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), andnoradrenergic and specific serotonergic antidepressants (NaSSAs) are used formoderate or severe cases as the first choice in terms of efficacy and tolerability.
However, superiority or inferiority were not shown among these new antidepressants.
Therefore, (a) watchful waiting and (b) new antidepressants (SSRIs, SNRIs, andNaSSAs) with the lowest price were selected as a comparator for each population.

Target(a) Mild depression and depressive symptoms

population(b) Moderate and severe depression and depressive symptoms
Population (a)：Watchful waiting

Comparator

Population (b)：New antidepressants (SSRIs, SNRIs, and NaSSAs)
with the lowest price

4. Evaluation of additional benefits
To evaluate the additional benefits of vortioxetine for patients with mild illness, themanufacturer performed a systematic review (SR). However, no randomized
controlled trials were identified. For patients with moderate or severe illness, themanufacturer revised a network meta-analysis by Cipriani et al. (2018) to Japaneseclinical settings by limiting interventions to new antidepressants (SSRIs, SNRIs, andNaSSAs) approved by Japanese authorities. As the search period for SR was also
extended, additional SR was performed. Data detected by SR were also included in
the network meta-analysis. As a result, no difference in efficacy and tolerability wasfound between vortioxetine and other new antidepressants.
The academic group made inquiries to the manufacturer about an SR forpatients with mild illness that includes all the new antidepressants. The results
showed that no randomized controlled trials for any new antidepressants wereidentified.
The academic group approved these results.
5. Result of cost-effectiveness analysis
According to the manufacturer’s submission, as no randomized controlled trials exist
for patients with mild illness, cost-effectiveness is “impossible to analyze” for thispopulation. The manufacturer submitted a cost-minimization analysis for patientswith moderate or severe illness. Milnacipran was selected as a comparator because
it is the cheapest among the new antidepressants. The manufacturer’s analysis
estimated treatment costs using the Markov model. However, the academic groupinsisted that the submitted Markov model has a high degree of uncertainty, forexample, in terms of treatment duration. Therefore, the academic group compared
the drug price per day assuming that efficacy and tolerability was equivalent. To
compare the drug price, the academic group used the following prescription doses
per day estimated by the National Claims Database.

Initial dose

Maximum

Average prescription(mg)dose (mg)dose per day (mg)

50150

75.2

10-2040

12.5 (CR)

50 (CR)

Sertraline

25100

49.8

Escitalopram

1020

11.9Milnacipran

25100

50.1

Duloxetine

2060

35.1

Venlafaxine

37.5

225

115.3

NaSSA

Mirtazapine

1545

20.3

OthersVortioxetine

102013.5

Generic name
Fluvoxamine

SSRI

SNRI

Paroxetine

19.1

The results of the cost-minimization analysis using the above estimation are shownbelow.

Target population

Comparator

ICER (JPY/QALY)

Mild

Watchful waiting“Impossible to analyze”

Moderate and severe

Milnacipran

Cost increase

As a sensitivity analysis, an additional analysis that compared cost with all the newantidepressants was performed. Cost increased if fluvoxamine, paroxetine, sertraline,
and mirtazapine were used as comparators. Cost of vortioxetine was lower comparedwith escitalopram, duloxetine, and venlafaxine.