Major depressive disorder (MDD) continues to be a highly prevalent psychiatric disorder. Over 5 million drug-treated MDD patients in the United States fail to respond adequately to treatment with one major class of antidepressant (stage 1 TRD), and just over two-thirds of stage 1 TRD patients fail treatment with two major classes of antidepressants (stage 2 TRD). Atypical antipsychotics—e.g., Abilify (Bristol-Myers Squibb/Otsuka Pharmaceutical’s aripiprazole), one of the few therapies approved for patients who do not respond adequately to antidepressant therapy—are increasingly used to augment antidepressants in TRD treatment. The unipolar depression market, including therapies approved for TRD, is a mature market with few remaining branded agents. Although opportunity remains for emerging drugs that can provide efficacy in TRD that is comparable to that of antipsychotic augmentation, marketers will be required to overcome reimbursement hurdles imposed by payers to ensure patient access.

Key products in the depression market include the following:

- Forest Laboratories/Pierre Fabre’s Fetzima (extended-release levomilnacipran), a serotonin and norepinephrine reuptake inhibitor (SNRI) that launched in December 2013 in the U.S. market for the treatment of MDD in adults.

- Takeda/Lundbeck’s Brintellix (vortioxetine), a serotonergic antidepressant that launched in January 2014 in the U.S. market for the treatment of MDD in adults.

- Sunovion’s Latuda (lurasidone), an atypical antipsychotic that launched for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate in July 2013 in the United States. This agent is also in clinical trials for MDD with mixed features (at least three symptoms of mania but an insufficient number of symptoms to qualify as mania).

Questions Answered in This Report:

  • How does use of select TRD therapies vary based on physician type and specific patient symptomology? What factors are primarily impacting physicians’ treatment decisions and MCO directors’ coverage decisions?

  • What is the current state of reimbursement for TRD therapies in the United States, and how will it likely change in the near future? How are recently launched Fetzima and Brintellix prescribed and perceived by physicians? Do physicians value an FDA-approved labeling claim for TRD?

  • How have/will physicians incorporate Fetzima, Brintellix, and Latuda into clinical practice? How has/will MCO reimbursement constraints, including tiering and formulary restrictions, impact uptake?

  • How do physicians expect to incorporate emerging agents (brexpiprazole, ALKS-5461, and GLYX-13) into clinical practice? What restrictions are MCO directors likely to impose? What does physician and payer receptivity to these emerging therapies imply for drug developers hoping to enter the TRD space?


In this report, we explore the use, reception, and formulary status of these key therapies for TRD in a survey of 70 primary care physicians (PCPs), 71 psychiatrists, 28 managed care organization (MCO) pharmacy directors (PDs), and three MCO medical directors (MDs). We also gauge payer and physician outlook on three emerging therapies: Otsuka/Lundbeck’s brexpiprazole, Alkermes’s ALKS-5461, and Naurex’s GLYX-13. By understanding the attitudes and expectations of prescribers and payers about current, recently approved, and emerging therapies used for the treatment of TRD, stakeholders can gain an understanding of the treatment paradigm and changing reimbursement climate for this patient population.

Markets covered: United States.

Primary research: 70 PCPs, 71 psychiatrists, 28 MCOPDs, three MCO MDs.

Epidemiology: 2012, 2017, and 2022 prevalent cases of stage 1 TRD and stage 2 TRD (Thase-Rush staging method).

Population segments: Where appropriate, our data and analyses are segmented by physician type or by the following patient populations: MDD, TRD, bipolar depression, and schizophrenia.

Author(s): Natalie Taylor, Ph.D.