Drug Expenditure, Price, and Utilization in the U.S. Medicaid: A Trend Analysis for SSRI and SNRI Antidepressants from 1991 to 2018.

BACKGROUND: SSRIs and SNRIs are antidepressants that have largely substituted old antidepressants like Monoamine Oxidase Inhibitors (MAOIs) and Tricyclic Antidepressants (TCAs). They have been widely used since 1987 when the FDA approved the first SSRI Fluoxetine and the first SNRI Venlafaxine in 1993. Since then, several new SSRIs and SNRIs have been approved and entered the market. Utilization, pricing, and spending trends of SSRIs and SNRIs have not been analyzed yet in Medicaid. AIM: To assess the trends of drug expenditure, utilization, and price of SSRI and SNRI antidepressants in the US Medicaid program, and to highlight the market share of SSRIs and SNRIs and the effect of generic drug entry on Medicaid drug expenditure. METHODS: A retrospective descriptive data analysis was conducted for this study. National pharmacy summary data for study brand and generic drugs were retrieved from the Medicaid State Outpatient Drug Utilization Data. These data were collected by the US Centers for Medicare and Medicaid Services (CMS). The study period was between 1991 and 2018. Study drugs include 12 different SSRI and SNRI brands and their generics available in the market, such as citalopram, escitalopram, paroxetine, fluoxetine, sertraline, venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran. Data were analyzed annually and categorized by total prescriptions (utilization), total reimbursement (spending), and cost per prescription as the proxy of the price for each drug. RESULTS: From 1991 to 2018, total prescriptions of SSRI and SNRI drugs rose by 3001%. Total Medicaid spending on SSRIs and SNRIs increased from USD 64.5 million to USD 2 billion in 2004, then decreased steadily until it reached USD 755 million in 2018. The SSRIs average utilization market share was 87% compared to 13% of the SNRIs utilization market share. About 72% of total Medicaid spending on the two groups goes to SSRIs, while the remaining 28% goes to SNRIs. Brand SSRIs and SNRIs prices increased over time. On the contrary, generic drugs prices steadily decreased over time. DISCUSSION: An increase in utilization and spending for both SSRI and SNRI drugs was observed. After each generic drug entered the market, utilization shifted from the brand name to the respective generic due to their lower price. These generic substitutions demonstrate a meaningful cost-containment policy for Medicaid programs. IMPLICATIONS FOR HEALTH POLICIES: Our findings show the overall view of Medicaid expenditure on one of the most commonly prescribed drug classes in the US. They also provide an important insight toward the antidepressant market and the importance of monitoring different drugs and their alternatives.

Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT.

BACKGROUND: Depression is usually managed in primary care and antidepressants are often the first-line treatment, but only half of those treated respond to a single antidepressant. OBJECTIVES: To investigate whether or not combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants results in better patient outcomes and more efficient NHS care than SNRI or SSRI therapy alone in treatment-resistant depression (TRD). DESIGN: The MIR trial was a two-parallel-group, multicentre, pragmatic, placebo-controlled randomised trial with allocation at the level of the individual. SETTING: Participants were recruited from primary care in Bristol, Exeter, Hull/York and Manchester/Keele. PARTICIPANTS: Eligible participants were aged ≥ 18 years; were taking a SSRI or a SNRI antidepressant for at least 6 weeks at an adequate dose; scored ≥ 14 points on the Beck Depression Inventory-II (BDI-II); were adherent to medication; and met the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, criteria for depression. INTERVENTIONS: Participants were randomised using a computer-generated code to either oral mirtazapine or a matched placebo, starting at a dose of 15 mg daily for 2 weeks and increasing to 30 mg daily for up to 12 months, in addition to their usual antidepressant. Participants, their general practitioners (GPs) and the research team were blind to the allocation. MAIN OUTCOME MEASURES: The primary outcome was depression symptoms at 12 weeks post randomisation compared with baseline, measured as a continuous variable using the BDI-II. Secondary outcomes (at 12, 24 and 52 weeks) included response, remission of depression, change in anxiety symptoms, adverse events (AEs), quality of life, adherence to medication, health and social care use and cost-effectiveness. Outcomes were analysed on an intention-to-treat basis. A qualitative study explored patients' views and experiences of managing depression and GPs' views on prescribing a second antidepressant. RESULTS: There were 480 patients randomised to the trial (mirtazapine and usual care, n = 241; placebo and usual care, n = 239), of whom 431 patients (89.8%) were followed up at 12 weeks. BDI-II scores at 12 weeks were lower in the mirtazapine group than the placebo group after adjustment for baseline BDI-II score and minimisation and stratification variables [difference -1.83 points, 95% confidence interval (CI) -3.92 to 0.27 points; p = 0.087]. This was smaller than the minimum clinically important difference and the CI included the null. The difference became smaller at subsequent time points (24 weeks: -0.85 points, 95% CI -3.12 to 1.43 points; 12 months: 0.17 points, 95% CI -2.13 to 2.46 points). More participants in the mirtazapine group withdrew from the trial medication, citing mild AEs (46 vs. 9 participants). CONCLUSIONS: This study did not find convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or a SNRI antidepressant over placebo in primary care patients with TRD. There was no evidence that the addition of mirtazapine was a cost-effective use of NHS resources. GPs and patients were concerned about adding an additional antidepressant. LIMITATIONS: Voluntary unblinding for participants after the primary outcome at 12 weeks made interpretation of longer-term outcomes more difficult. FUTURE WORK: Treatment-resistant depression remains an area of important, unmet need, with limited evidence of effective treatments. Promising interventions include augmentation with atypical antipsychotics and treatment using transcranial magnetic stimulation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN06653773; EudraCT number 2012-000090-23. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 63. See the NIHR Journals Library website for further project information.

Cost-Effective Drug Switch Options After Unsuccessful Treatment With an SSRI for Depression.

OBJECTIVE: Multiple treatment options are available for patients who do not respond to initial treatment for major depressive disorder. Previous results show that bupropion, sertraline, and venlafaxine are comparable in terms of therapeutic effectiveness following unsuccessful treatment with citalopram. In this study, we extended these results by incorporating costs of treatment to determine if one option was more cost-effective relative to others. METHODS: In the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial, 727 patients were randomly assigned to a switch drug treatment during level 2; 239 (33%) were assigned to bupropion, 238 (33%) to sertraline, and 250 (34%) to venlafaxine. For each study medication, the total costs included the costs of the medication, other concomitant medication and antidepressants, and health care facility utilization. Effectiveness was measured as remission and response. Cost-effectiveness was assessed as net health benefits. Stochastic analysis was performed by using the bootstrapping method. RESULTS: During level 2, mean medication costs were significantly higher for venlafaxine than for bupropion and sertraline ($968, $607, and $703, respectively). There were no significant differences among the switch medications in costs for other medications and health care facility utilization. Although the total costs were significantly different for the three medications (p=.025), none of the pairwise differences between medications were significant. Also, after jointly estimating costs and effects, the analyses found that net health benefits were not significantly different among the three drugs. CONCLUSIONS: After unsuccessful treatment with citalopram, the switch options of bupropion, sertraline, and venlafaxine were not significantly different from each other in terms of cost-effectiveness.

[Economic evaluation of desvenlafaxine in the treatment of major depressive disorder in Spain]. / Evaluación económica de la desvenlafaxina en el tratamiento de la depresión mayor en España.

INTRODUCTION: The objective of this analysis was to evaluate the clinical and economic value of the use of 50mg-desvenlafaxine compared to the usual care (mix of duloxetine and venlafaxine) in the outpatient treatment of major depressive disorder after first line treatment failure (relapse) in Spain. MATERIALS AND METHODS: A Markov model was used to follow up a cohort of major depressive disorder patients for one year after failure of first-line treatment with a serotonin-specific reuptake inhibitor and estimate outcome measures (percentage remission and depression-free days) and accrued and direct costs incurred during outpatient treatment of major depressive disorder. In order to obtain the efficacy data related to the treatment alternatives, a literature review of clinical trials was performed. A panel of clinical experts validated the use of clinical resources employed in the estimation of economic outcomes together with model assumptions. The analysis was performed in 2014 from the perspective of the National Health System. RESULTS: Due to fewer discontinuations, initiating second line treatment with desvenlafaxine was associated with more depression-free days and a higher percentage of patients in remission versus usual care: 1.7 days and 0.5%, respectively. This was translated into lower drug and events management costs, and an overall cost reduction of €108 for the National Health System. CONCLUSIONS: In patients who have not responded to a first-line serotonin-specific reuptake inhibitor therapy, desvenlafaxine-50mg was clinically similar in effectiveness, but a less costly option, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of major depressive disorder patients from a payer (National Health System) perspective in Spain.

Increased use of antidepressants in Wuhan, China: a retrospective study from 2006 to 2012.

OBJECTIVE: The aim of this study was to investigate the trend of antidepressant use and analyze the daily cost of antidepressants in Wuhan, China. MATERIAL AND METHODS: The data on the expenditure of antidepressants in Wuhan from 2006 to 2012 were retrospectively analyzed based on the defined daily dose (DDD) method recommended by the World Health Organization. In addition, the daily cost of antidepressants was calculated for the pharmacoeconomic evaluation. RESULTS: The overall sales of antidepressants increased by 566.7% over the 7-year period. The utilization of antidepressants increased annually from 1.067 DDDs per 1000 inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven by an increase in the use of selective serotonin reuptake inhibitors (SSRIs), which accounted for about 60% of antidepressant use. Notably, the use of traditional Chinese patent medicines (TCMs) approved to treat depression in China in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305 in 2012. The daily drug cost analysis indicated that selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low-cost advantage. CONCLUSIONS: Antidepressants were increasingly used over the study period. Among them, SSRIs followed by SNRIs were the most commonly used. After the approval for the treatment of depression, TCMs were generally accepted by physicians and patients. The low-cost advantage allowed TCAs to be used in the antidepressant therapy.