We thank da Silveira and colleagues [1] for raising the challenges in determining depression and anxiety trajectories in chronic disease. We agree with the authors that depression and anxiety should not be considered an unavoidable consequence of chronic disease [2]. We also agree that the trajectories of psychological symptoms are affected by many things (e.g., life experience, coping skills). Indeed, our team is actively exploring accessible psychological treatments to facilitate coping and adjustment [3]. We also share a common goal to further clarify the true course of depression and anxiety among these populations.

In the context of a meta-analysis, one key obstacle to gaining this clarity is the diversity among studies’ samples and methodology. The risk of including diverse studies is that there is too much heterogeneity to draw appropriate conclusions [4, 5]. We employed numerous measures to mitigate excessive heterogeneity, such as specifying a minimum number of studies that could be included in moderator analysis, and examining only depression and anxiety trajectories (which is why we excluded measures such as stress and coping).

Nonetheless, as the authors point out [1], our moderator analyses yielded some discrepant findings within subgroups (e.g., depression instrument and study country) [6]. We agree that these results within subgroups seem implausible; however, they do not signal inaccuracies in data extraction or analysis. Importantly, we would not wish for any reader to interpret these results without considerable caution. This heterogeneity likely reflects differences in sampling, measurement, and analytic methods not captured in simple subgroup analysis. For example, while our inclusion criteria were limited to studies using a validated measure of depression or anxiety, there were still various measures used. As the authors raise [1], some of these are more suitable than others in chronic disease populations, which we also raise in our discussion.

We attempted to address the discrepant results in the discussion of our paper [6]. Importantly, we emphasised findings that appeared consistent across studies. For example, most people with chronic disease follow a trajectory of stable and non-clinical symptoms. Our discussion also emphasises the importance of individual patient data meta-analysis that may overcome some of the issues related to heterogeneity and allow a more sophisticated exploration of moderators.

If there are concerns about the validity of our results, we welcome any in-depth review and re-analysis of our findings. We consciously provided detailed supplementary material, containing each study and its extracted data, to assist with such efforts. These data could be used to explore other moderators or different categorisation of studies. For example, the authors raised concerns regarding the data presented in Figures 2 and 3 and had questions about the prevalence of participants following less common trajectories [1]. Our supplementary materials contain raw prevalence and trajectory data from each study, for more detailed exploration [6].

The authors suggest that it would have been helpful to examine trajectories based on patients meeting formal diagnostic criteria. We agree that this would be very informative; however, few studies examined diagnostic status, hence our focus on symptoms. We would encourage further work exploring this issue.

Finally, the authors seek clarification regarding statements about psychotropic medication [1], though it is unsure whether they are referring to our decision to exclude studies where the entire sample was undergoing treatment (e.g., studies typically examining trajectories of response following psychiatric treatment), our discussions about psychotropic medication use in the individual studies, or something else. As such, it is difficult to clarify further. We sincerely welcome additional questions and discussion.

The authors have no conflicts of interest to declare.

This research was enabled by funding from a Macquarie University Research Fellowship (MQRF; A.J.S.) and Australian National Health and Medical Research Council (NHMRC).

Amelia J. Scott and Blake F. Dear were responsible for drafting the letter. Ashleigh B. Correa and Madelyne A. Bisby provided critical review.

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