Vortioxetine (Trintellix) is a serotonin reuptake inhibitor indicated for the treatment of MDD in adults. The recommended starting dosage is 10 mg per day for adults and the dosage may be increased to a daily maximum of 20 mg or reduced to 5 mg daily for individuals unable to tolerate higher doses. The recommended starting dosage for adults 65 years of age and older is 5 mg daily, and caution is advised in treating elderly patients with doses greater than 10 mg. The manufacturer submitted a price of $2.81 per 5 mg, $2.95 per 10 mg, and $3.20 per 20 mg tablet. CADTH previously reviewed vortioxetine for the treatment of MDD in 2015, but the submission was voluntarily withdrawn by the manufacturer.
The manufacturer submitted a cost-utility analysis considering vortioxetine versus other antidepressants for the treatment of MDD episodes as a first-line treatment from the perspective of a Canadian publicly funded health care payer over a one-year time horizon. Comparators included serotonin-noradrenaline reuptake inhibitors (duloxetine and venlafaxine), selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), and two treatments with different mechanisms of action (bupropion and mirtazapine). The model consisted of a combined decision tree and Markov model in which a hypothetical cohort of treatment-naive patients with MDD start in the model in the decision tree and progress to subsequent lines of treatment in the model. Patients transition to subsequent treatment due to relapses, short- and long-term adverse events (AEs), or lack of treatment efficacy. The manufacturer submitted a network meta-analysis (NMA) of the comparative efficacy and rate of withdrawal due to AEs between vortioxetine and comparators, based on a recent publication by Cipriani et al., which included 522 randomized controlled trials. The manufacturer stratified treatments according to dose and transformed the results by applying the odds ratio (OR) to placebo values for remission rates and discontinuation due to AEs. Discontinuation for first-line treatment and short- and long-term AEs were assumed to occur over the first two-month cycle only, with no discontinuation occurring during second- or third-line treatment. Health-state utility values were obtained from the REVIVE study5 for “baseline depression,” “remission,” and “no remission” health states. Utility decrements due to AEs were also applied in the model. Health care utilization and costs for health states were based on estimates from clinical experts. Drug acquisition costs for vortioxetine were based on the manufacturer’s submitted price and unit drug prices for comparators were obtained from the Ontario Drug Benefit program.
In the manufacturer’s base case, vortioxetine was associated with both higher costs and QALYs when compared to all other comparators. Based on the sequential analysis, bupropion is the preferred option if a decision-maker is willing to pay $49,000 per QALY; duloxetine is the preferred option if a decision-maker is willing to pay between $50,000 and $89,000 per QALY; and vortioxetine is preferred if the decision-maker is willing to pay more than $89,000 per QALY.
Version: FINAL (with redactions)
Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
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