Royal Australian and New Zealand College of Psychiatry (RANZCP) guidelines have international impact. We read with enthusiasm the 2020 update of the mood disorders guidelines (Malhi et al., 2020a). There is much of value, certainly regarding medications. However, we found section 9 (‘Response to Treatment’, pp. 85–90) problematic in discussions of treatment-resistant depression (TRD) and the relatively new concept of ‘difficult-to-treat depression (DTD)’. The guidelines argue that ‘DTD is extremely heterogeneous, as any number and all manner of “difficulties” can contribute to non-response’ (p. 86). We agree, but do not see this as a weakness of the DTD model – rather a recognition of clinical reality of relevance to management. Of more concern, it is stated that ‘[DTD] does not sufficiently alter the focus of management’ (p. 86). We beg to differ.
Rather than TRD or DTD, adoption of a ‘response perspective’ model (proposed by Malhi et al., 2020b) is recommended (section 9.4, pp. 87–90). This model focuses on ‘response (outcome) and responsiveness (of the depression)’ (p. 87). While optimism about treatment is to be encouraged, the model appears to assert that virtually all patients with depression will eventually achieve sustained and substantial benefit from antidepressant treatment, and that the exceptions were wrongly diagnosed:
the paradigm does allow for instances in which a specific treatment responsivity has not been found and all reasonable measures have been ineffective in achieving recovery. These are instances in which an alternative diagnosis is the likely cause of the depressive illness, for example, a stroke or neoplasm. (p. 89)
While we endorse the need for further assessment and investigation of any patient who has not achieved recovery following multiple treatments, we believe that this statement, and the responsivity paradigm itself, ignores the clinical reality that such situations exist and are not simply related to some alternative diagnosis. Of note, remission rates beyond step 2 in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study were less than 15% (Rush et al., 2006). This is precisely the point of the DTD model: it advocates regular review and re-assessment of treatment direction, acknowledging that in some situations the focus needs to shift from recovery to optimising symptom control and maximising psychosocial function (McAllister-Williams et al., 2020). The ‘response perspective’ ignores the prognostic importance of treatment history, clinical course and presentation in guiding treatment strategy. It sadly sidesteps the risk of a potentially endless sequence of treatment trials with ever-increasing side-effect burden while ignoring tractable reasons for poor outcomes.
Might the RANZCP guidelines be adjusted to address these concerns?
Footnotes
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: In the last 5 years, R.H.M.-W has received fees from American Center for Psychiatry & Neurology, United Arab Emirates, British Association for Psychopharmacology, European College of Neuropsychopharmacology, International Society for Affective Disorders, Janssen, LivaNova, Lundbeck, My Tomorrows, OCM Comunicaziona s.n.c., Pfizer, Qatar International Mental Health Conference, Sunovion, Syntropharma, UK Medical Research Council and Wiley; grant support from National Institute for Health Research Efficacy and Mechanism Evaluation Panel and Health Technology Assessment Panel; and non-financial support from COMPASS Pathways. S.T.A. is a consultant to Neuronetics, LivaNova, Janssen, Sage Therapeutics and Genomind. He also receives research support from Compass Pathways and Neuronetics. C.R.C. has received research support from Bristol Myers Squibb, the Stanley Medical Research Institute, the National Institute of Mental Health, NeoSync, Inc., LivaNova, the Taylor Family Institute for Innovative Psychiatric Research, The American Foundation for Suicide Prevention, Assurex Health Inc., The Brain & Behavior Research Foundation, the August Busch IV Foundation and the Barnes-Jewish Hospital Foundation; he is a part-time employee of the John Cochran VA Medical Center in St. Louis and serves as the Lead Investigator of the RECOVER VNS trial in the United States. K.D. has received honorarium for attending advisory boards, acting as a consultant or being a member of the speaker bureau for Boehringer-Ingelheim, Gedeon-Richter, Johnson & Johnson, Livanova, Lundbeck, Pfizer and Recordati. P.B.F. is supported by an NHMRC Investigator award (1193596). In the last 3 years, he has received equipment for research from Medtronic and Nexstim and is a founder of TMS Clinics Australia and Resonance Therapeutics. C.K.L. is supported by an NHMRC Investigator award. In the last 3 years, she has served on a Janssen advisory board. In the last three years, P.M. has received honoraria from Janssen-Cilag Australia (advisory board membership; speaker) and Sanofi Hangzhou (speaker). A.J.R. has received consulting fees from Compass Inc., Curbstone Consultant LLC, Emmes Corp., Evecxia Therapeutics, Inc., Holmusk, Johnson & Johnson (Janssen), LivaNova, Neurocrine Biosciences Inc., Otsuka-US and Sunovion; speaking fees from LivaNova and Johnson & Johnson (Janssen); and royalties from Guilford Press and the University of Texas Southwestern Medical Centre, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on two patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S and Wilson AS; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, and Paddock S. H.A.S. serves as a scientific adviser to Cerebral Therapeutics Inc., LivaNova PLC, MECTA Corporation and Neuronetics Inc. He receives honoraria and royalties from Elsevier, Inc. and Oxford University Press. He is the inventor on non-remunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST) (US8712532), titration in the current domain in ECT (US9789310) and the adjustment of current in ECT devices (US10583288), each held by the MECTA Corporation. He is also the originator of magnetic seizure therapy (MST). A.H.Y. has received payment for lectures and advisory boards for the following companies: AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma and COMPASS. He is a consultant to Johnson & Johnson and Livanova. He has received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova. He is a Principal Investigator on studies funded by LivaNova, Janssen and COMPASS, and Chief Investigator on a study funded by Novartis. He does not hold shares in pharmaceutical companies.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs: RH McAllister-Williams 
https://orcid.org/0000-0001-9966-1834
PB Fitzgerald
https://orcid.org/0000-0003-4217-8096
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