افسردگی و درد: ارزیابی اثربخشی هزینه و مطلوبیت هزینه داروهای ضد افسردگی

Background Although depression and chronic pain frequently co-occur, there is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants in the presence of these two conditions. From the perspective of healthcare provider, the current study aims to compare the cost-effectiveness and cost-utility of antidepressants in a national cohort of depressed patients with and without comorbid pain conditions. Methods Adult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan (n = 96,501). By using remission as effectiveness measure and quality-adjusted life years (QALYs) as utility measure, the cost-effectiveness and cost-utility were compared across selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), as well as by the presence of comorbid painful physical symptoms (PPS). Results SSRIs dominated SNRIs in both the cost-effectiveness and cost-utility regardless of comorbid PPS. In comparison with TCAs, SSRIs were likely to be the cost-effective option for patients without PPS. In patients with PPS, the cost-utility advantage for SSRIs over TCAs varied with threshold willingness-to-pay levels. Comorbid PPS may be considered an effect modifier of the cost-utility comparisons between SSRIs and TCAs. Conclusions For depressed patients without PPS, SSRIs are likely to be cost-effective in improving remission rates and QALYs compared to TCAs and SNRIs. However, to improve cost-utility in those with comorbid PPS, people need to choose between SSRIs and TCAs according to threshold willingness-to-pay levels. Future research is warranted to clarify the impacts of different pain conditions on the economic evaluations of pharmacological treatments in patients with depression.

Painful physical symptoms (PPS) have been shown to precede the onset of a new depressive episode (Barry et al., 2013), and to contribute to prolongation of the duration of depressive mood (Ohayon and Schatzberg, 2003). In a community survey, the severity of PPS, including headache, pain in the abdomen, back pain and other musculoskeletal pains, has been found to correlate with the severity of depressive symptoms. Presence of PPS deteriorates physical, occupational and socio-professional activities in patients with depression (Ohayon and Schatzberg, 2010). With the evidence that comorbid PPS may be associated with a poor response to antidepressants (Bair et al., 2004, Carter et al., 2012, Kroenke et al., 2008 and Leuchter et al., 2010), and with increased healthcare costs (Gameroff and Olfson, 2006, Greenberg et al., 2003 and Pan et al., 2013a), the results of cost effectiveness analysis (CEA) comparing antidepressant treatments may be influenced in the presence of comorbid PPS. Depression and pain have been reported to be among the most burdensome diseases globally (Vos et al., 2012). These two conditions contribute to the highest loss of quality-adjusted life years (QALYs) (Subramaniam et al., 2013). In patients with depression, the severity of PPS has been shown to be associated with disability (Ohayon and Schatzberg, 2010) and considered a strong predictor of impaired quality of life (Bair et al., 2004). Given the impacts of PPS on quality of life of depressed patients, a cost utility analysis (CUA) comparing antidepressants is wanted when presence of PPS is taken into consideration. In CEA, costs are considered alongside disease-specific outcomes, e.g., treatment response to antidepressants. This kind of economic evaluation is limited by the narrow focus on a single measure of effectiveness outcome. There can be difficulties in evaluating treatments that impact on more than one outcome, e.g., social functioning and quality of life. A CUA is similar to a CEA but it considers costs alongside a utility based outcome measure, usually QALYs. The advantage of CUA is that the results can be compared across different disease areas. Although tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) were shown to be probably more effective than selective serotonin reuptake inhibitors (SSRIs) in reducing PPS (Bair et al., 2004 and Peveler et al., 2006), results from other clinical trials revealed similar response rate and pain relief across antidepressant groups in patients with both depression and pain (Qaseem et al., 2008). Whether and how individual antidepressants differ in the effectiveness of depression treatment and pain relief remains to be determined. According to a previous review (Pan et al., 2012), most of the existent economic evaluations of antidepressants were based on modelling and relatively few CEA and CUA studies have been conducted with patients of depressive disorders in real-world settings (Hosak et al., 2000, Peveler et al., 2005, Serrano-Blanco et al., 2006a, Serrano-Blanco et al., 2006b and Serrano-Blanco et al., 2009). Among the economic evaluations addressing individual antidepressants in patients with selective pain disorders, a systematic review showed that even for duloxetine (a SNRI), no relevant cost or cost-effectiveness data could be identified in high quality studies (Lunn et al., 2014). In patients with depression and comorbid PPS, evidence regarding the cost-effectiveness (or cost-utility) comparisons across individual antidepressants remain wanting. Therefore, from the perspective of healthcare providers, we conducted both CEA and CUA among individual antidepressants in the current study based on the National Health Insurance Research Database (NHIRD) records of the entire national assemblage of adult depressed patients in Taiwan. Because antidepressants might differ in their effects on the management of PPS, we hypothesise that results of CEA and CUA comparing antidepressant treatments differ by the presence of comorbid PPS. The objective was to compare the cost-effectiveness and cost-utility across antidepressant categories and to test whether and how the presence of PPS could affect the economic evaluations of antidepressants in a real-world setting.

A total of 96,501 adult individuals met the inclusion criteria. The number of subjects with comorbid PPS was 77,067. Patients with PPS were older; they were more likely to be females and less likely to have newly-diagnosed depression. With regards to baseline healthcare utilisation, patients with PPS had higher use of outpatient services and higher baseline total healthcare costs than those without PPS (Table 1).