Channelling a response to difficult-to-treat depression: A need for ratiocination,not rash assassination!

We read with great interest the comments by the posse of professors from around the world led by McAllister-Williams and were suitably gratified by the positive endorsement of our recently published mood disorders guidelines (MDcpg²⁰²⁰; Malhi et al., 2021), which incidentally are also available as summaries (Malhi et al., 2020a, 2020b). We were heartened for example by their pleasing comment regarding the content of the MDcpg²⁰²⁰ that ‘there is much of value, certainly regarding medications’ (McAllister-Williams et al., 2021), but were somewhat at a loss as to why they had stopped short of descriptions used by others such as ‘intellectually dazzling’ (Rosenman, 2021). Furthermore, we were positively exercised by their unsympathetic description of our critique of treatment-resistant depression (TRD) and difficult-to-treat depression (DTD) as ‘problematic’.

Their response was all the more mystifying given that they agree that DTD is extremely heterogeneous in terms of the factors that can contribute to non-response. However, they then seek to reframe this as ‘a recognition of clinical reality’ which they presume informs management. It is thus that our turn to agree materializes, as we too approve of the broader perspective that DTD potentially provides especially in comparison to TRD. But alas, we are unable to shake off our sense of uneasiness provoked by the portrayal of our innovative thinking as problematic. Therefore, after some deep and devout deliberation, we surmise that perhaps the authors have misunderstood our proposed Channelling Response Paradigm.

It is crucial to note that our humble paradigm is fundamentally different to DTD and TRD. This is because the latter essentially defines a ‘kind of depression’ or depressive state – albeit on the basis of treatment characteristics. Put another way, DTD is literally that ‘subtype’ of depression that is difficult to treat, and similarly, TRD is seeking to delineate a sub-category of depression that is refractory to treatment. In both instances, the terms (DTD and TRD) are defining depression, that is, the illness, and do so on the basis of whether it responds to therapy and how difficult it is to manage.

In contrast, our channelling response paradigm describes an approach. It outlines the manner in which depression could and should be addressed. Importantly, the paradigm does not attempt to define depression itself; instead, the focus is shifted to achieving a much broader management perspective in which many strategies may be needed to overcome depression. In other words, it is designed to inculcate recognition of the fact that different sets of treatments may be needed to achieve a satisfactory outcome. To this end, we carefully outline the principles of the channelling response paradigm in the MDcpg²⁰²⁰ (p. 89), noting that it is important at every juncture of management. Indeed, we stipulate that from the outset of management, it is imperative to evaluate the response to any intervention that is administered, and that both the diagnosis of the disorder and its optimal management should be regularly reformulated. Underscoring this point further, the channelling response paradigm encourages and extends the key point of DTD as outlined by the authors, the ‘regular review and re-assessment of treatment direction’. Specifically, this requires reviewing the treatment at all times in great detail, and while pharmacotherapy is discussed in depth, the response perspective does not ignore the ‘prognostic importance of treatment history, clinical course and presentation’ in relation to guiding treatment strategy.

In fact, all of these aspects are deemed to be critical and have been outlined in Finding the channel (p. 89; MDcpg²⁰²⁰). And importantly, the need to address the multiple psychosocial determinants of depression is at the core of the channelling response paradigm. Hence why, Actions that include the institution of sleep hygiene, exercise and diet; address substance misuse; and target social and psychological causes of depression take pole position and are mandatory throughout the MDcpg²⁰²⁰.

A major advantage (and distinguishing feature) of the channelling response paradigm is that it applies to the management of all depression, and its principles should be applied throughout treatment. It is not targeting a subset of depression, such as DTD or TRD, and in fact the approach is intended to be universal and not at all limited to special circumstances. Furthermore, it does not seek to define a subtype or introduce a strategy after a set number of failures, as is the case with DTD or TRD, which in comparison artificially creates supposed phenotypes of depression.

In sum, the channelling response paradigm is a set of ideas that focuses the attention of both the clinician and the patient on potential outcomes. It is a forward-looking, hopeful and positive approach that shifts the emphasis of management towards response, remission and functional recovery, with the development of future resilience in mind.