This was a cross-sectional, observational study conducted by BPR Pharma (London, UK) in Brazil, Canada, and Spain between April 15 and May 18, 2021. The study design has been reported in detail in the previous paper in this series [22]. In brief, data were collected through an online self-completed survey. Participants were recruited through an existing online panel of consumers and healthcare providers.

Patient respondents were aged 18–70 years and had been diagnosed with depression by a physician, were currently using a prescribed antidepressant, and reported having experienced emotional blunting in the last 6 weeks in response to a validated screening question [23]: ‘Emotional effects of depression and treatment vary, but may include, for example, feeling emotionally “numbed” or “blunted” in some way; lacking positive emotions or negative emotions; feeling detached from the world around you; or “just not caring” about things that you used to care about. Have you experienced such emotional effects during the last 6 weeks?’.

Enrollment quotas were imposed with respect to age (50% aged ≥ 50 years) and sex (60% female). Patients who had not been diagnosed with depression by a doctor and those who responded ‘No’ to the screening question or who were not in the acute or remission phase of depression were excluded from study participation. Patients currently employed by a pharmaceutical company or market research agency were also excluded.

The study was approved by an institutional review board (Veritas IRB, Montreal, QC, Canada), was conducted in accordance with the European Pharmaceutical Market Research Association (EphMRA) code of conduct, and adhered to General Data Protection Regulation (GDPR) and all local market laws regarding data protection. Patients had previously consented to participate in research; however, informed consent was also obtained specifically for this study.

The severity of emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) [23, 24]. The ODQ comprises 26 questions about emotional experiences during the past week, for which respondents are asked the extent to which they agree or disagree. Questions are split across five domains: general reduction in emotions, reduction in positive emotions, emotional detachment from others, not caring, and antidepressant as cause. The ‘antidepressant as cause’ domain is only completed by patients who are currently taking antidepressants, and explores the perception of a potential link between the patient’s current treatment and their experience of emotional blunting. The ODQ total score ranges from 26 to 130 points, with higher scores indicating more severe emotional symptoms.

Functioning was assessed by means of the Functioning Assessment Short Test (FAST), a brief self-report instrument designed to assess problems experienced in daily functioning [25]. The FAST covers 24 items across six domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. Patients were instructed to select the degree of difficulty associated with each item (‘no difficulty’, ‘mild difficulty’, ‘moderate difficulty’, ‘severe difficulty’, or ‘don’t know’). For the purposes of this survey, the period of recall was ‘during this acute or remission phase of depression.’ FAST total score ranges from 0 to 72, with higher scores indicating greater functional impairment.

General well-being was assessed using the World Health Organization-Five Well-being Index (WHO-5) [26]. This short self-reported questionnaire assesses the degree of agreement over the past 2 weeks with five simple statements covering different aspects of well-being; agreement scores range from 0 (at no time) to 5 (all of the time). WHO-5 total score ranges from 0 to 25. Higher scores indicate a greater sense of well-being, with a total score of less than 13 considered indicative of poor well-being.

Patients were asked which of a list of symptoms they had experienced during their current phase of depression (including emotional blunting), and were asked to rate the severity of the symptoms experienced on a scale of 1 (not at all severe) to 7 (extremely severe). Patients also rated the impact of their symptoms [namely, emotional blunting, lack of interest (i.e., anhedonia), mood symptoms, physical symptoms, anxiety, and cognitive symptoms] on different aspects of daily life; namely, their ability to function at work, in their home/family life, and in their social life, as well as on their overall quality of life. Impact was rated on a 7-point scale, with a score of 6 or 7 indicating a significant impact.

The analysis population comprised all respondents who met the inclusion criteria and completed the online survey. Patients who failed to complete the survey or who completed the survey much faster than average were excluded from the final sample. Any patient who responded ‘don’t know’ to more than one item for any FAST domain was excluded from the analysis of that domain. For patients who responded ‘don’t know’ to just one item in any FAST domain, the mean score for the other items answered in that domain was used to impute the missing value (as per the scale guidance). Respondents with a missing score for any domain were removed from the calculation of FAST total score (a missing score would result from them having responded ‘don’t know’ to more than one item in that domain).

Data were analyzed for the overall patient population and by phase of depression (self-reported): acute or remission. The acute phase was defined as: ‘A time when your symptoms are at their worst or most severe and for which you use antidepressant treatment.’ The remission phase was defined as: ‘A time when your symptoms have improved significantly and you are already feeling better, but you may or may not still experience some minor symptoms. You are still taking antidepressant medication.’

Results are presented descriptively using means and standard deviations (SDs) for continuous variables, and frequencies and percentages for categorical variables. Comparisons were performed for continuous measures using t tests and for proportions using Z tests. The relationship between ODQ total score and FAST and WHO-5 total scores was explored using Pearson correlation and multivariate regression analyses. Regression was assessed on: (a) demographic variables (age band, sex, education, country); (b) symptoms of depression (anxiety, physical symptoms, cognitive symptoms, mood symptoms); and (c) ODQ total score. Variable sets (a), (b), and (c) were entered hierarchically as blocks. Block (a) was force entered, and variables in blocks (b) and (c) were entered only if they had a statistically significant effect (determined using backward and forward selection). Statistical significance determined by either method was considered valid. For FAST total score, the analysis was also performed using the five ODQ domain scores instead of the ODQ total score.

Data were analyzed by The Stats People (Sevenoaks, UK) using MERLIN tabulation software and Microsoft Excel. Significance was set at p < 0.05.