This study evaluated the relationship between patient functioning and specific residual symptom domains (core mood, insomnia, anxiety, somatic symptoms) and pain symptoms in a large group of patients with MDD who responded after receiving acute treatment. Anxiety was the most prevalent residual symptom, followed by core mood symptoms. The strength of the association between the residual symptom domains studied and patient functioning differed depending on the type of symptoms. A more marked association was found for residual core mood symptoms. Residual insomnia was less strongly related to patient functioning, and residual somatic symptoms were not associated.
To our knowledge, this is the first study to investigate the role of specific residual symptoms on patient functioning in MDD. Most publications about residual symptoms in MDD focus on their description and on their relationship to relapse and recurrence of depression [6, 22–27]. More recent publications have evaluated their relationship to time to remission [6, 28]. Few studies have specifically investigated the relationship between residual symptoms and functional impairment, but instead have focused on the overall impact of these symptoms on functioning without a separate analysis of the type of residual symptom [1, 8, 29].
As reported previously, residual symptoms are very common after acute treatment, even in remitters [6, 22, 23]. In the present investigation, we found that almost 90% of remitters had at least one residual symptom domain of mild intensity. This is similar to figures reported by Nierenberg et al.  and Ioveno et al. . Similar to other studies, the most common residual symptom domain in our patients was anxiety [6, 26]. Other studies have reported residual insomnia  and sleep disturbances [6, 22] to be the most common residual symptoms domains. These differences may be due to the use of different scales and definitions. Development of a consensus on the definition and measurement of residual symptoms would be desirable to enable results between studies to be compared, thus improving understanding.
Interestingly, we found the strongest association between patient functioning and residual core mood symptoms, and we also found a significant interaction with pain and anxiety. The absence of pain increased the chances of normal functioning, regardless of the presence of residual anxiety. However, the absence of residual anxiety increased the chances of normal functioning only if pain was not present. Of note, we found residual insomnia significantly less strongly related to patient functioning than residual core mood symptoms. In addition, no association was found for residual somatic symptoms. It is remarkable that baseline depression severity and previous depression episodes were not significantly related to functional impairment. This further supports the previous finding that residual symptoms are more important than previous episodes of depression in the prognosis of the patient .
The different degree of association of each residual symptom with patient functioning might have prognostic implications and requires further investigation. In line with this, several recent studies tried to identify which specific residual symptoms are predictive of relapse or recurrence [16, 26, 30, 31]. Residual anxiety symptoms were found to be predictive of relapse [26, 30, 31]. The picture for residual insomnia was less clear, with both positive [16, 30] and negative associations reported . Although preliminary, these findings suggest that some residual symptoms present a greater risk for relapse than others.
This study has the following limitations: The primary study from which our data were drawn was not designed to assess residual symptoms, and our results are based on a post-hoc analysis. Our analysis has inherent limitations of post-hoc analysis; measures were those used in the source study. Antidepressant history, before baseline, was not collected, therefore percentage of naïve patients and already treated patients are unknown. This analysis has included a selected population of patients with MDD; patients who had a response to acute antidepressant treatment. This may limit the generalizability of the results to other types of patients not included in this analysis. Our research focused on selected residual symptoms domains and did not include domains such as fatigue or other symptoms not included in the HAMD-17. We also cannot rule out the possibility that a small proportion of the symptoms reported might have been treatment-emergent and not residual.