Associations between commonly used patient-reported outcome tools in postpartum depression clinical practice and the Hamilton Rating Scale for Depression

Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy, resulting in a substantial health-related quality of life burden for mothers, children, and partners (Callaghan et al. 2010; Centers for Disease Control and Prevention 2018; Centers for Disease Control and Prevention 2019; De Sisto et al. 2014; Ko et al. 2017; Martin et al. 2019; Moore Simas et al. 2019; Roberts et al. 2013; Vismara et al. 2016). In the USA, an estimated 11.5% of new mothers experience symptoms of PPD, with global estimates of 17.7% (Hahn-Holbrook et al. 2017; Ko et al. 2017).

Clinicians treating perinatal women commonly use the Edinburgh Postnatal Depression Scale (EPDS) or Patient Health Questionnaire (PHQ)-9 as PPD screening tools. Both the EPDS and PHQ-9 are patient-reported instruments and therefore provide unique perspective into the patient’s experience of their symptoms. Given the increasing focus on patient-centred care, understanding and incorporating patient’s voice into the assessment of health outcomes can facilitate shared decision-making, early diagnosis, individualized care, and patient satisfaction with treatment. The EPDS is a validated screening tool for PPD widely used to assess the likelihood of clinical depression and recently recommended by the American College of Obstetricians and Gynecologists (ACOG Committee Opinion No. 757 2018; Cox et al. 1987; Smith et al. 2016). Although the EPDS was developed as a screening tool, it is often used as an outcome measure in PPD studies and clinical practice (Appleby et al. 1997; McCabe-Beane et al. 2016; Sharp et al. 2010). The EPDS has been shown to perform well when compared to clinician-reported tools such as structured clinical interviews and more consistently than other patient-reported tools such as the Beck Depression Inventory (Beck et al. 1988; Bennett et al. 2004; Ji et al. 2011; Spinelli et al. 2013). The PHQ-9 is a general depression screening questionnaire that is also commonly used to screen for PPD, particularly in primary care settings, has been found to be highly specific for identifying PPD, and has comparable psychometrics, sensitivity, and specificity to the EPDS (Flynn et al. 2011; Gjerdingen et al. 2009; Kroenke et al. 2001; O'Connor et al. 2016; Sidebottom et al. 2012; Sit and Wisner 2009; Zhong et al. 2014).

The 17-item Hamilton Rating Scale for Depression (HAMD-17) is widely used as a primary endpoint in major depressive disorder (MDD) and PPD clinical trials and is commonly required by regulatory bodies (e.g. Clayton et al. 2015; Hantsoo et al. 2014; Papakostas et al. 2012). As an established clinician-reported outcome measure, it is regarded as the gold standard assessment in clinical trials, demonstrating stability over time and allowing for comparison of treatment effects between studies (Ji et al. 2011; Khan et al. 2002; Kim et al. 2014). However, given its complexity and length of time to complete, the HAMD-17 is less commonly used to assess depression in clinical practice. While EPDS and PHQ-9 severity group cut-off scores have been reported (Ji et al. 2011; Kroenke et al. 2001; McCabe-Beane et al. 2016), no mapping of EPDS or PHQ-9 scores to predict HAMD-17 scores has previously been reported. Understanding the direct relationship between patient-reported outcomes as measured either by the EPDS or by the PHQ-9 and the clinician-reported HAMD-17, based on evidence from a PPD-specific population, could further validate these screening tools in the identification of patients in need of treatment given symptom severity and enhance early diagnosis in this vulnerable population.

The present post hoc analysis aimed to bridge the existing interpretation gap and examine the relationship between the EPDS, PHQ-9, and HAMD-17 instruments. These post hoc analyses used an integrated dataset combining the data from three randomized, double-blind, trials of intravenous brexanolone compared to intravenous placebo in women with moderate and severe PPD (Kanes et al. 2017; Meltzer-Brody et al. 2018a). More specifically, using the HAMD-17 as the criterion measure, this study aimed to (1) assess the association between the current EPDS and PHQ-9 definitions of remission and the HAMD-17 definition of remission, (2) assess the association between the EPDS and PHQ-9 item and total scores with the HAMD-17 total score, (3) develop a mapping equation to permit the estimation of HAMD-17 scores from EPDS and PHQ-9 scores.

In total, 199 patients provided EPDS, PHQ-9, and HAMD-17 data at day 30 and were thus eligible for the present analysis. While all analyses were conducted on the pooled sample, the patient demographics and baseline characteristics are presented overall and by treatment arm for information (Table 1). Of the 199 patients included in these analyses at baseline, most patients were white (121, 61%), 74 (37%) were black or African-American, and 35 (18%) were Hispanic or Latino. A higher proportion of patients had onset of PPD within 4 weeks of delivery than the third trimester. The mean EPDS total score at day 30 was 9.04 (SD = 6.84), the mean PHQ-9 total score was 6.76 (SD = 6.52), and the mean HAMD-17 total score was 10.56 (SD = 8.47), with minimum and maximum scores 0–27, 0–25, and 0–31, respectively.

PPD is frequently unrecognized, undiagnosed, and inadequately treated (Cox et al. 2016). A more nuanced understanding of how commonly used screening tools such as the EPDS and PHQ-9 relate to clinical trial outcomes, such as the HAMD-17, may help address failures in diagnosis and treatment. The observed large associations between EPDS and PHQ-9 total score and HAMD-17 total score, as well as moderate associations of remission definitions, suggest that patients’ self-reports of their symptoms generally align with clinician-ratings, such as the HAMD-17, that may be prohibitively time and training intensive to obtain and further validate the ability of these screening tools to identify patients with PPD symptoms. Once a patient is diagnosed, management generally follows a stepped care approach, wherein patients with mild symptoms are treated through low-intensity interventions and those with symptoms that do not respond, are more severe, or present acutely are typically offered pharmacologic interventions, either alone or adjunctive to low-intensity interventions (Meltzer-Brody et al. 2018b). The observed pattern of results in these analyses, wherein higher scores on EPDS and PHQ-9 are associated with more severe symptoms as assessed by HAMD-17, may help clinicians who have identified and diagnosed PPD patients to understand and discuss with the patients what treatments are likely appropriate. Primary care physicians, obstetricians, and gynaecologists and even paediatricians who administer an EPDS or PHQ-9 may have a better ability to recognize which women are likely to receive benefit from low-intensity interventions, such as psychosocial support, and those that may warrant prompt referral for more intensive care. Clinicians seeking to practice shared decision-making regularly need to draw on and interpret a high volume of new clinical evidence in order to describe and discuss available options, alongside possible benefits or harms (Price 2005). Being able to understand and translate the relationship between the HAMD-17 data commonly reported as evidence of treatment efficacy in clinical trials and the EPDS or PHQ-9 data being captured in clinic will hopefully assist clinicians in more confidently and readily interpreting trial evidence to present during shared decision discussions. Given limitations in healthcare resources and availability of specialists, confidence in the use of these tools for valid screening and treatment decision-making may also help ameliorate stresses to the healthcare system.

The large associations observed between total scores are notable given that the measures differ in terms of patient versus clinician-rating, as well as in content, with EPDS designed specifically for the perinatal period, PHQ-9 initially designed for general depression, and HAMD-17 designed to assess changes in symptom severity. The moderate associations observed between EPDS and PHQ-9 item scores and HAMD-17 total score are in line with expectations, as individual item scores are expected to show more variability than summed total scores. Furthermore, as an advance to the current reliance upon individual outcome measure cut-off values to interpret scores, the current study also conducted regression analysis to provide two simple mapping equations that can easily be applied in any clinical setting.

The present post hoc analysis demonstrates large and statistically significant associations between patient-reported EPDS and PHQ-9 scores and the clinician-reported HAMD-17 and in an integrated efficacy dataset of PPD trials and provides the first mapping equations to permit the estimation of HAMD-17 total score from known EPDS or PHQ-9 scores. Given the role of the HAMD-17 as the gold standard criterion for evaluating the efficacy of treatments in clinical trials, the results presented here provide tools to aid interpretation of clinical trial data in clinical practice, thus aiding informed decision-making for multiple stakeholders in regulatory and clinical settings and shared decision-making in clinical practice for this critical population of women with PPD.