The IDeAS in MIDAS: ‘Keeping it real!’

As much as guidelines are a cornerstone in the development to a more rational and more helpful medicine, they can be a dull read. Not so the Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders (1): In relative brevity, the authors touch on an impressive array of topics and do justice to many facets of mood disorders, integrating the individual and the environment as well as the psychology and the biology. They write scientifically and down to earth at the same time – all the while in very readable style accompanied by excellent illustrations. Respect. (Baethge, 2021)

We thank Professor Baethge (2021) for his ‘wicked’ review of the Clinical Practice Guidelines (CPGs), and for his earnest critique of the approach advocated within MIDAS (Malhi et al., 2020). His feedback is important and welcome, and largely in keeping with our own broader appeal for further research to be undertaken in all aspects of the management of mood disorders.

Antidepressants clearly work (Cipriani et al., 2018); however, there are many complexities and constraints in real-world practice that require careful consideration when extrapolating from research trials. MIDAS stands for medication, increase-dose, augment and switch, and while it is correct that King Midas himself came to be viewed somewhat negatively, the use of MIDAS in the guidelines is intended to reflect the ability he possessed to turn everything he touched to gold. In other words, it is meant to have metaphysical significance, in that by attending to the management of depression, the illness can be ‘transformed’ and recovery can be achieved.

It is to this end that the MIDAS framework provides a template that is intended to guide the pharmacological management of depression once an initial antidepressant has been prescribed. And while we concur that the evidence is sparse, the initial approach of increasing antidepressant dose (ID) draws on clinical experience and the fact that, with some antidepressants, titration is necessary to achieve broader receptor engagement. For example, with a medication such as venlafaxine, increasing dose increases recruitment of noradrenergic neurotransmission while maintaining serotonergic enhancement. Furthermore, in practice, there is usually some degree of partial response, albeit a flicker, that initiates consideration of increasing the antidepressant dose.

We also welcome the addition of the possibility of combining antidepressants in patients that are non-responsive and in particular the addition of ‘antagonists of presynaptic α₂ auto-receptors … to monoamine reuptake inhibitors’, which includes the oft-cited combination of mirtazapine and venlafaxine, also referred to as ‘California rocket fuel’ (Malhi et al., 2008).

Finally, the last step in MIDAS is switching, and this is perhaps the most inevitable when a medication proves to be ineffective or only has a partial response. However, the main thrust of the MIDAS paradigm is to ensure that there is time to reflect and reformulate and some additional steps have at least been considered prior to switching, such as increasing dose or augmentation. And while we agree that the evidence concerning switching within and outside of class is yet to provide a definitive answer, the focus of our considerations regarding switching in the guidelines is to ensure that the choice to switch is informed by knowledge of pharmacological mechanisms, hence the recommendation of seven different Choice agents, each of which has different mechanisms of action.

In conclusion, we welcome the thoughtful comments from Christopher Baethge, and are grateful that MIDAS and the guidelines as a whole have prompted careful deliberation of our management recommendations. ‘Booyakasha – right back at ya’.