Introduction
The concept of health was defined by the World Health Organization in 1948 as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” [
1]. This was later refined into five dimensions of health-related quality of life (HRQoL) encompassing physical, social, psychological, overall life satisfaction/wellbeing and perceptions of health status at the 1993 International Consensus Conference [
2]. HRQoL is used to assess both functional outcome and quality of life (QoL) across disease states and has been demonstrated to be impaired in depressed patients compared to both the general population and to people with chronic medical conditions such as diabetes, arthritis, and heart disease [
3‐
5]. It is therefore important to understand what factors influence HRQoL in depression and how these influence response to treatment. The five dimensions of HRQoL can be assessed using tools such as the Short Form 36 Health Status Survey (SF-36) [
6] and European Quality of Life-5 Dimensions (EQ-5D) [
7] and although studies have previously assessed the effectiveness of antidepressant treatments on HRQoL [
8‐
13] further research is needed in order to improve our understanding of factors related to HRQoL and its improvement during treatment. Two possible moderators of HRQoL in depression are somatic and pain symptoms. Many depressed patients present with somatic symptoms [
14] and there is a strong association between depression and painful symptoms in primary care [
15]. It is known that painful symptoms adversely affect treatment outcomes in depression [
16], but less is known about their impact on HRQoL outcomes.
The European Factors Influencing Depression Endpoints Research (FINDER) observational study [
17‐
19] was designed to increase understanding of the factors that influence HRQoL outcomes for clinically depressed outpatients receiving antidepressant medication in routine primary and secondary care. In this study, pain and its impact on functioning were also assessed using patient-reported measures. A strength of this study is that it included patients with other chronic medical comorbidities that may influence HRQoL and outcomes, and so is more reflective of the clinical populations found in primary care than those from randomized controlled trials in which greater use of exclusion criteria is normal. The findings from naturalistic observational studies such as FINDER may therefore be generalizable to a larger population and can be used to provide direction for further research [
20].
The primary objective of this paper is to estimate the HRQoL of a primary care depressed population at baseline (untreated) and 3 and 6 months after initiation of antidepressant treatment. A shared secondary objective was to determine the factors associated with HRQoL at baseline and 6 months. Additional, post hoc secondary objectives specific to the UK sample were: to describe the impact of caseness for depression at baseline on HRQoL; to describe the impact of pain (explained medical cause/unexplained medical cause) at baseline on HRQoL; to describe changes in overall pain and pain interference outcomes by pain cohort (explained medical cause/unexplained medical cause); and to summarize antidepressant use by pain cohort (explained medical cause/unexplained medical cause).
The authors are not aware of any other paper which has sought to bring together outcomes as measured by QoL with the factors that influence outcomes as described above, making this an innovative paper with a particular relevance to primary care.
Discussion
The results of this study found that HRQoL (as measured by the SF-36 and EQ-5D) in patients with a first or new episode of depression presenting in UK primary care was below that previously reported in healthy populations. HRQoL improved during the first 3 months following antidepressant initiation, with more limited improvement from 3 to 6 months. The findings of this study in UK primary care patients are therefore similar to those of the full European FINDER study with respect to the primary objective. Similarly, the SF-36 MCS score at the end of the study had not normalized (50) and was at least 1 SD lower than for the general population. The study also showed minimal change on SF-36 PCS, probably reflecting a ceiling effect as a mean score of 50 represents the score for the general population. These results are consistent with other clinical studies [
8‐
13].
The independent variables significantly associated with HRQoL at baseline in the UK sample include SSI-somatic score, HADS-D, HADS-A, pain cohort, gender, occupational status, and age. Patients with adverse sociodemographics, greater general medical and depressive illness burden have been identified with poorer QoL [
27]. The authors’ finding that a higher SSI-somatic score was associated with a poorer HRQoL supports previous findings of an inverse relationship between somatic symptoms and QoL [
28]. Moreover, a recent cross-sectional study in a large population of primary care patients with depression showed that numerous characteristics of somatic symptoms (number, disability, persistence) were associated with a decreased QoL [
29].
Higher SSI-somatic scores were also associated with worse HRQoL outcomes over time, highlighting the continuing impact of (nonpainful) somatic symptoms on HRQoL. Somatic symptoms have been found to be associated with pain and improvement in pain outcomes in the European cohort of the FINDER study [
30]. As the presence of painful symptoms has been shown to compromise outcomes of antidepressant treatment [
16,
31], so the results of this study suggest that nonpainful physical symptoms as well as painful symptoms should be taken into account when maximizing treatment response in depression.
An important finding was that those patients who switched antidepressant treatment within the same antidepressant class (e.g., SSRI) had a poorer HRQoL (SF-36 MCS, EQ-5D health state value) outcome over the 6-month follow-up period than those who had no change in treatment or who switched to a different antidepressant class. Switching between antidepressant classes (e.g., SSRI to SNRI) was not significantly associated with poorer HRQoL outcome. These findings suggest that if a change in treatment is necessary, it may be more advantageous in terms of HRQoL to switch from one antidepressant class to another. This should be explored in more detail in a controlled setting.
The association of sociodemographic and depression-related factors with changes in HRQoL remain consistent with the European analysis [
19]. Pain cohort (no pain or either explained or unexplained pain) was not significantly associated with change in HRQoL in the UK sample, despite significant results in the univariate analysis and an association with baseline HRQoL. Pain was associated with worse HRQoL (SF-36 MCS only) in the European analysis (
P = 0.026) using the overall pain VAS score rather than pain cohorts [
19]. It is likely that lack of sensitivity of the pain cohort compared to that of the pain VAS score, in addition to the smaller sample size in the UK, account for this discrepancy.
Only a few previous studies have used EQ-5D to assess HRQoL in depressed patients in primary care [
13,
32,
33]. In a naturalistic, longitudinal, primary care study in Sweden [
33], the EQ-5D VAS scores at baseline (40) and after 6 months of antidepressant treatment (63) were similar to those found in the present study (47 and 68, respectively, at baseline and 6 months). The same was true for the EQ-5D health state values. Nevertheless, despite improvement during 6 months of follow-up, the mean EQ-5D scores in the present study remained below the European population norms by almost 1 SD [
26].
Using the patient-rated HADS-D score of 8 or greater as a cut-off due to high sensitivity and specificity in general practice [
22], the majority of patients (82%) recruited into the UK FINDER study met the criteria for caseness for depression. This supports the view that UK GPs involved with this study were good at diagnosing clinical depression. The baseline mean SF-36 summary scores (MCS 19.2 and PCS 47.4) for patients who met the criteria for caseness correspond closely to the mean values reported in a French primary care study [
32] of patients with major depressive disorder defined by the Diagnostic and Statistical Manual of Mental Disorders, IVth revision (MCS 21.1 and PCS 43.6).
The reduction in pain severity (measured using the overall pain VAS) for the whole patient cohort was only statistically significant at the 6-month post baseline assessment. However, when patients with no/mild pain were separated from those with moderate/severe pain, there were significant reductions in the overall pain VAS score at both 3 and 6 months in patients with medically explained and those with unexplained pain, which exceeded the 12 mm threshold for a minimum clinically significant difference reported by Kelly [
34]. Despite the above finding, the cohort with unexplained pain at baseline still had moderate pain at the end of the study (mean overall pain VAS 36.4). Furthermore, pain interference with daily activities was still significantly impaired in the unexplained pain cohort compared with the no/mild pain cohort (mean VAS 33.9 vs. 10.2). This observation suggests that by 6 months, the antidepressant treatments that were given in the study (which were mainly SSRIs) were neither very effective at treating the painful somatic symptoms in depression nor at minimising the associated disability.
Antidepressant use patterns in this UK general practice study were in accordance with the National Institute for Health and Clinical Excellence guidelines for depression [
35], which were published halfway through recruitment into this study (May 2004 to September 2005); the majority of patients received SSRIs as first-line treatment. The pattern of antidepressant use was similar for patients with unexplained pain and without pain, in contrast to the explained pain cohort, in which TCAs were more commonly used in the first 3 months and combination therapy in the second 3 months. This lack of differentiation indicates that GPs either do not take pain into account when selecting antidepressants for depressed patients when there is no comorbid medical condition present or feel that using different classes of antidepressant would not be of value.
This study supports the view that different antidepressant strategies may be required to reduce both disability and residual pain symptoms to normal values in the management of depressed patients with painful somatic symptoms. A recent Sequenced Treatment Alternatives to Relieve Depression (STAR-D) report [
36] focusing on poorer treatment outcome with an SSRI when painful physical symptoms are present reinforces this point. Furthermore, assessment and treatment of depression in primary care should incorporate pain measurement. This could be encouraged in the UK by the adoption of pain assessment in the mental health section of the quality and outcomes framework [
37] that provides voluntary targets to GPs with financial incentives.
Research into the association of painful symptoms of depression and poorer HRQoL outcome warrants further investigation in a controlled setting, in longer studies, and using different treatment modalities including comparisons of different classes of antidepressant.
The most significant strength of the study is that it is one of the largest prospective, observational studies of HRQoL during treatment for depression in a primary care setting. It reflects the reality of prescribing and outcomes in UK general practice over a 6-month time period. Furthermore, the use of robust validated measures exploring depression caseness, HRQoL and pain add to the existing literature and can help inform clinical practice and future research.
The study has several limitations in addition to those common to observational studies due to the lack of randomization, such as selection and observer bias. First, the observation period was limited to 6 months, so it is unclear if HRQoL would become comparable to population norms with further treatment, or if a deficit would remain for those with pain on current treatment. Conversely, due to the episodic nature of depression, it is possible that improvement in depression and related HRQoL in some subjects over the 6-month period represents the natural course of the illness rather than improvement related to any treatment given. Furthermore, without a control group, improvement could represent regression towards the mean. Second, during the second 3-month period of the study, 15–22% of patients in each group were not receiving drug treatment, and it is unclear how this may have affected HRQoL outcome overall and in the different pain cohorts. Finally, the results do not reflect the complete spectrum of patients presenting with depression in primary care, but those in whom mutual agreement between clinician and patient has resulted in a course of antidepressants. The ThREshold for AntiDepressant response (THREAD) study [
38] conducted in UK general practice found that many patients, albeit with mild to moderate depression, declined to receive antidepressants.
The UK GP patients in this study, in contrast with the mixed primary and secondary care populations of the European FINDER study [
17], presented with a shorter history of depression: mean duration of depression (5.3 vs. 8.5 years), mean number of depressive episodes (1.3 vs. 1.8) in the previous 24-month period for those with at least one previous episode, and a less frequent history of anxiety/panic disorder (28.7% vs. 51.1%) in the previous 24-month period.
Acknowledgments
The FINDER study was funded by Eli Lilly and Co. Ltd., Windlesham, UK and Boehringer Ingelheim GmbH, Ingelheim, Germany. Eli Lilly and Co. Ltd. was involved in all stages of the study design, data collection, data analysis, manuscript preparation and publication decisions. Dr. Lenox-Smith is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. The authors take full responsibility for the content of the paper but thank Roben Das Gupta from Boehringer Ingelheim Ltd. for his early input into the manuscript, Deirdre Elmhirst, PhD, for her medical writing services in preparing the first draft of the manuscript and Andy Bradley (Lilly) for editing assistance.