Abstract
Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.
Highlights
Many medications have proven efficacy in major depressive disorder (MDD) [1, 2], but frequently and even with multiple medication exposures, they fail to improve MDD symptoms [3,4,5,6,7]; one third of individuals do not achieve full symptomatic remission [3], and even fewer meet criteria for both symptomatic and functional remission [8]
‘Incomplete response’ is not an all-or-nothing phenomenon, but rather a continuum that ranges from partially responsive depression (PRD), to treatment-resistant depression (TRD), to ‘multi-therapyresistant MDD (MTR-MDD)’ [9], to ‘refractory depression’, which implies an absence of response to all currently available treatments
We provide a number of recommendations, each based on the might be useful for both individuals with MDD and clinicians, especially in averting the development of ‘therapeutic nihilism’ [16]
Summary
Many medications have proven efficacy in major depressive disorder (MDD) [1, 2], but frequently and even with multiple medication exposures, they fail to improve MDD symptoms [3,4,5,6,7]; one third of individuals do not achieve full symptomatic remission [3], and even fewer meet criteria for both symptomatic and functional remission [8]. We recommend (with moderate consensus, 75%) that it is possible to assess ineffective past/current antidepressant treatment attempts, but only if properly documented, that is, based on subjective recollection or standardised instruments to assess psychiatric history and previous treatments (see below), and on clinical documentation, such as pharmacy, hospital, or other health records This documentation can be used to confirm some degree of adherence to the failed treatments, and to screen people with depressive symptoms for previous episodes of mania, hypomania, or sub-threshold bipolarity, since these individuals should be excluded (see below). The most reliable method to assess adherence is to perform a blood test to measure the concentration of the medication in the plasma (which would allow the recognition of fast and slow metabolisers), even though it may increase the participants’ burden during the trial This suggestion was clearly supported by the experts, systematic use of plasma level monitoring in TRD/PRD definitions is not current practice. Has the second medication been administered at a dose equal or superior to the minimum licensed dose and for at least 4 weeks?
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
