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Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan

Published online by Cambridge University Press:  23 June 2023

Daniela C. Fuhr*
Affiliation:
Department of Prevention and Evaluation, Leibniz Institute of Prevention Research and Epidemiology, Bremen, Germany Health Sciences, University of Bremen, Bremen, Germany Department of Health Services and Policy Research, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK
Siham Sikander
Affiliation:
Human Development Research Foundation, Rawalpindi, Pakistan Department of Primary Care and Mental Health, University of Liverpool, Liverpool, UK
Fiona Vanobberghen
Affiliation:
Department of Medicine, Swiss Tropical and Public Health Institute, Allschwil, Switzerland University of Basel, Basel, Switzerland MRC International Statistics and Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
Benedict Weobong*
Affiliation:
Department of Social and Behavioural Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
Atif Rahman
Affiliation:
Department of Primary Care and Mental Health, University of Liverpool, Liverpool, UK
Helen A. Weiss
Affiliation:
MRC International Statistics and Epidemiology Group, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
*
Corresponding authors: Daniela C. Fuhr; Email: [email protected] Benedict Weobong; Email: [email protected]
Corresponding authors: Daniela C. Fuhr; Email: [email protected] Benedict Weobong; Email: [email protected]
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Abstract

Background

Mothers with perinatal depression can show different symptom trajectories and may spontaneously remit from depression, however, the latter is poorly understood. This is the first study which sought to investigate predictors of spontaneous remission and longer-term recovery among untreated women with perinatal depression.

Methods

We analysed data from two randomised controlled trials in women with perinatal depression in India and Pakistan. Analyses were restricted to women in the control groups who did not receive active treatment. Generalised estimating equations and logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for within-person correlation.

Results

In multivariable analyses, remission was associated with a husband who is not working (adjusted OR, aOR = 2.04, 95% CI 1.02–4.11), lower Patient Health Questionnaire-9 score at baseline (aOR = 0.43, 95% CI 0.20–0.90 for score of ≥20 vs. 10–14) and better social support at baseline (aOR = 2.37, 95% CI 1.32–4.27 for high vs. low social support).

Conclusions

Women with low baseline severity may remit from perinatal depression with adequate social support from family and friends. These factors are important contributors to the management of perinatal depression and the prevention of clinical worsening, and should be considered when designing low-threshold psychological interventions.

Type
Research Article
Creative Commons
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press

Impact statement

Perinatal depression is a disabling mental condition that can significantly affect mothers after child birth and within the first year postpartum. The majority of women who develop depression after birth may show mild or moderate symptoms only, that have the potential to resolve over time without providing treatment. However, there is paucity of evidence of what may trigger spontaneous remission of perinatal depression and which factors are associated with this. With this study, we shed light on factors that may determine remission and recovery of symptoms. We do this by analysing data of mothers with depression who did not receive active treatment for their symptoms and followed them up over 6 months’ time.

Introduction

Perinatal depression is a disabling mental condition that has its onset during pregnancy or within the first year after delivery, and can significantly impair psycho-social functioning (DSM-V, 2013; Woody et al., Reference Woody, Ferrari, Siskind, Whiteford and Harris2017). In a recent systematic review and meta-analysis, the estimated prevalence of perinatal depression globally was higher among women in low- and middle-income countries (18.7% postnatally and 19.2% prenatally) than among women in high income countries (9.5% postnatally and 9.2% prenatally) (Woody et al., Reference Woody, Ferrari, Siskind, Whiteford and Harris2017). Mild and moderate symptoms of depression are most common (Hegel et al., Reference Hegel, Oxman, Hull, Swain and Swick2006), however, for perinatal depression specifically, heterogeneity of symptoms has been reported (Santos et al., Reference Santos, Tan and Salomon2017). Low, medium and chronic symptom trajectories for perinatal depression have been established (Santos et al., Reference Santos, Tan and Salomon2017) but these may not necessarily follow expected patterns and may be transient (Baron et al., Reference Baron, Bass, Murray, Schneider and Lund2017). It is speculated that symptom trajectories may be influenced by specific biological, social and psychological risk factors. These include prior history of psychopathology, high parity, low social support, lack of education and exposure to negative life events (Yim et al., Reference Yim, Tanner Stapleton, Guardino, Hahn-Holbrook and Dunkel Schetter2015; Ahmed et al., Reference Ahmed, Bowen, Feng and Muhajarine2019). However, we currently lack knowledge about modifiable risk factors and these still need to be established (Baron et al., Reference Baron, Bass, Murray, Schneider and Lund2017). The heterogeneity of symptoms of perinatal depression led to a call to personalise treatment to improve the response to treatment and facilitate recovery (Johansen et al., Reference Johansen, Robakis, Williams and Rasgon2019). Our previous research on the effectiveness of brief psychological interventions for women with perinatal depression supports this tailored approach to treatment and suggests that a low-intensity psychological intervention for perinatal depression delivered by peers may be most suitable for women whose depression is mild and acute rather than chronic and severe (Fuhr et al., Reference Fuhr, Weobong, Lazarus, Vanobberghen, Weiss, Singla, Tabana, Afonso, de Sa, D’Souza, Joshi, Korgaonkar, Krishna, Price, Rahman and Patel2019; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ain, Bibi, Bilal, Bibi, Liaqat, Sharif, Zulfiqar, Fuhr, Price, Patel and Rahman2019; Singla et al., Reference Singla, MacKinnon, Fuhr, Sikander, Rahman and Patel2021).

Research also reports spontaneous remission for perinatal depression (Yazici et al., Reference Yazici, Kirkan, Aslan, Aydin and Yazici2015; Maselko et al., Reference Maselko, Sikander, Turner, Bates, Ahmad, Atif, Baranov, Bhalotra, Bibi, Bibi, Bilal, Biroli, Chung, Gallis, Hagaman, Jamil, LeMasters, O’Donnell, Scherer, Sharif, Waqas, Zaidi, Zulfiqar and Rahman2020). Spontaneous remission is attained when sub-clinical levels of symptoms of depression are achieved without treatment, determined for example by a below-threshold score on a standardised symptom severity measure (Whiteford et al., Reference Whiteford, Harris, McKeon, Baxter, Pennell, Barendregt and Wang2013). It has been more extensively studied for major depressive disorder, and a systematic review found that among people with untreated depression, 53% had spontaneous remission within 1 year (Whiteford et al., Reference Whiteford, Harris, McKeon, Baxter, Pennell, Barendregt and Wang2013). Spontaneous remission may be associated with the presence of other mental health problems, the duration of the overall episode and severity of symptoms, individual genetic vulnerabilities, personality traits as well as environmental supports and stressors (Paykel, Reference Paykel1998; Rush et al., Reference Rush, Kraemer, Sackeim, Fava, Trivedi, Frank, Ninan, Thase, Gelenberg, Kupfer, Regier, Rosenbaum, Ray and Schatzberg2006). It is especially common among people who show mild or moderate symptoms of depression only (Posternak and Miller, Reference Posternak and Miller2001; Hegel et al., Reference Hegel, Oxman, Hull, Swain and Swick2006), and this has been confirmed for pregnant and post-partum women as well (Yazici et al., Reference Yazici, Kirkan, Aslan, Aydin and Yazici2015; Santos et al., Reference Santos, Tan and Salomon2017; Maselko et al., Reference Maselko, Sikander, Turner, Bates, Ahmad, Atif, Baranov, Bhalotra, Bibi, Bibi, Bilal, Biroli, Chung, Gallis, Hagaman, Jamil, LeMasters, O’Donnell, Scherer, Sharif, Waqas, Zaidi, Zulfiqar and Rahman2020). Although there is evidence that women with perinatal depression may show spontaneous remission, and improve symptoms over time, the predictors for spontaneous remission and recovery (defined as remission at both 3 and 6 months) still need to be investigated further. This will strengthen the evidence base for the prevention and treatment of perinatal depression, and increase our understanding of the contribution of active treatment to remission and recovery.

In this study, we conducted secondary analyses of data from two completed randomised controlled trials (RCTs) in India and Pakistan which demonstrated the effectiveness of a peer-delivered psychological intervention on symptoms of perinatal depression (Fuhr et al., Reference Fuhr, Weobong, Lazarus, Vanobberghen, Weiss, Singla, Tabana, Afonso, de Sa, D’Souza, Joshi, Korgaonkar, Krishna, Price, Rahman and Patel2019; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ain, Bibi, Bilal, Bibi, Liaqat, Sharif, Zulfiqar, Fuhr, Price, Patel and Rahman2019). We analysed data from women with perinatal depression in the control groups of the two trials who did not receive active treatment. The objectives of this study were a) to understand factors associated with remission among women with untreated perinatal depression in India and Pakistan; b) to explore factors associated with longer-term recovery; and c) to investigate if these factors differ by country.

Methods

We pooled data from two RCTs which sought to investigate the effect of a task-shifted psychological intervention (The Thinking Healthy Programme-Peer delivered [THPP]) on the severity of symptoms for perinatal depression and remission (Vanobberghen et al., Reference Vanobberghen, Weiss, Fuhr, Sikander, Afonso, Ahmad, Atif, Bibi, Bibi, Bilal, de Sa, D’Souza, Joshi, Korgaonkar, Krishna, Lazarus, Liaqat, Sharif, Weobong, Zaidi, Zuliqar, Patel and Rahman2020). The results from the trials (an individually randomised trial in urban Goa, India; and a cluster RCT in rural sub-districts of Rawalpindi, Pakistan) have been published previously (Fuhr et al., Reference Fuhr, Weobong, Lazarus, Vanobberghen, Weiss, Singla, Tabana, Afonso, de Sa, D’Souza, Joshi, Korgaonkar, Krishna, Price, Rahman and Patel2019; Sikander et al., Reference Sikander, Ahmad, Atif, Zaidi, Vanobberghen, Weiss, Nisar, Tabana, Ain, Bibi, Bilal, Bibi, Liaqat, Sharif, Zulfiqar, Fuhr, Price, Patel and Rahman2019). Data from these trials were collected during 2014–2016. Participants were recruited from antenatal centres and primary health care in Goa, and from community-based households in Rawalpindi. In both countries, participants were aged ≥18 years, in their second or third trimester of pregnancy at enrolment, and scored ≥10 on the Patient Health Questionnaire-9 (PHQ-9). The intervention was delivered by peers who were women from the local community who had children themselves and had gone through the experience of pregnancy, childbirth and raising a family.

Women in the control group received enhanced usual care. This included the following: First, women and their antenatal health care providers (antenatal health care providers were gynaecologists in Goa, and local government employed community health workers in Rawalpindi) were informed about the PHQ-9 score and depression status of participants. We also provided referral information to the gynaecologist (in Goa) and to the primary care physician (in Pakistan) who received training on the mental health gap intervention guide and referrals. Second, participants were provided with an information leaflet containing information about self-care during pregnancy and local self-referral pathways to mental health care. In addition to enhanced usual care, women in the intervention group received the THPP, a task-shifted psychological intervention based on behavioural activation which was delivered in 6–14 sessions over 6 months.

The primary trial outcome was remission, defined as the absence of depressive symptoms (PHQ-9 < 5) at 3 months post birth. The PHQ-9 was translated and validated in the local languages. Secondary outcomes included remission at 6 months, and recovery (PHQ-9 < 5 at both 3 and 6 months post birth).

Data were collected on the following baseline characteristics of the mother: Age in years; level of education (no formal education, up to primary education, up to secondary education, beyond secondary education); employment status (employed or not being currently employed); total number of children; previous miscarriage or still birth (none, one or more); sex of the current baby (girl or boy); family structure (nuclear or extended, i.e., living on their own with family or extended families living together); financial empowerment (yes/no), that is, asking if mother is able to put aside money for their own personal use or not; debt (yes/no), that is, asking if anyone in household is currently in debt or not; and if the mother has experienced any domestic violence in the past 3 months (yes/no). Perceived social support of the mother was measured with the Multidimensional Scale of Perceived Social Support. We also asked the mother about her expectation and how she would find the THPP intervention prior to starting it (not/little useful, somewhat useful, moderately useful, very useful). We collected data on her husband, namely, his level of education (no formal education, up to primary education, up to secondary education, beyond secondary education), employment status (employed or not being currently employed) and the number of months the husband had been away from home in the past 6 months (less than 1 month, 1 month or more).

For this paper, analyses were restricted to participants randomised to the control group of the trials. Data analysis was conducted using Stata version 17.0 (Stata, 2022). We used generalised estimating equations (GEEs) to adjust for within person correlation, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Factors associated with remission were estimated by conducting a repeat measures analysis using data from both 3- and 6-month visits for each woman. We adjusted for country and month of visit (a priori), and factors associated with missing outcome data (‘minimally adjusted model’). We performed complete case analyses, that is, visits were included if remission data were available for that visit. We conducted sensitivity analyses using multiple imputation as an alternative strategy to account for missing outcome data. This imputed missing outcome data with 25 imputations. The final multivariable model included variables independently associated with the outcome, determined by starting with a full model of variables associated with the outcome with p < 0.1 in the minimally adjusted model, and retaining them if they were independently associated with the outcome in the multivariable model (p < 0.05). Country was an a priori effect-modifier, and effect-modification by country was assessed for the final models by fitting an interaction term of country and each exposure variable.

The study was performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments. Ethical approval was obtained from the Institutional Review Boards at the London School of Hygiene and Tropical Medicine, Sangath (the implementing institution in India), the Indian Council of Medical Research, the University of Liverpool and the Human Development Research Foundation (the implementing organisation in Pakistan). All study participants provided their informed consent prior to their inclusion in the study.

Results

In India, 118,260 women were assessed for eligibility over a 2-year period, of whom 6,369 were screened using the PHQ-9, and 333 were eligible. Of these, 280 (84.1%) women were enrolled into the trial (140 randomly allocated per group). Over the same period, 1,910 pregnant women in Pakistan from 40 village clusters were assessed. Of these, 1,731 were screened using the PHQ-9, and 572 were eligible. Of these 570 (99%) were enrolled into the trial (283 in the intervention group and 287 in the control group).

Baseline characteristics of the 427 participants randomised to the control groups are shown in Table 1. Participants in India were slightly younger than those in Pakistan (mean 25.3 and 27.3 years, respectively) and had less education overall (55.7% of those in India had no formal education or primary education only, compared with 26.9% in Pakistan). The majority of participants in both countries did not work, however, participants in India were less likely to be in debt and reported being more financially empowered than those in Pakistan (78.6% vs. 54.7%). A higher proportion of participants in India had fewer than two children, and reported fewer miscarriages or stillbirths than participants in Pakistan. Participants in India tended to have less severe depression than those in Pakistan (71.4% with moderate depression in India vs. 58.2% in Pakistan), and to have had depression for a shorter period (35.7% with chronicity ≥12 weeks at baseline assessment vs. 80.3% in Pakistan). Participants in India reported higher perceived social support but had lower expectations of the usefulness of psychological counselling.

Table 1. Baseline characteristics of participants with untreated perinatal depression

Abbreviation: MSPSS, Multidimensional Scale of Perceived Social Support.

Overall, 56 (13.1%) of participants were not seen at both 3 and 6 months (i.e., lost to follow-up). Of these, 9 participants were in India (6.4% loss to follow-up), and 47 were in Pakistan (16.5% loss to follow-up). Factors independently associated with loss to follow-up were country (p = 0.003), and whether the woman worked outside the home (p = 0.01). These were adjusted for in subsequent analyses.

The prevalence of remission at 3 months and 6 months, respectively, were each lower among participants in Pakistan than those in India (44.1% vs. 50.8% at 3 months; 44.7% vs. 59.7% at 6 months; Appendix 1 of the Supplementary Material). This difference was statistically significant (minimally adjusted OR [aOR] = 1.55; 95% CI 1.08–2.22; p = 0.02; for the two endpoints combined; Table 2).

Table 2. Factors associated with remission (PHQ < 5 at 3 or 6 months)

Abbreviation: MSPSS, Multidimensional Scale of Perceived Social Support.

* Using both 3- and 6-month data, assuming a constant association of exposure at these two time points, and adjusted for month of visit and factors associated with loss to follow-up (namely, country and women’s occupation).

The association between other factors and remission are presented in Table 2.

In the multivariable model (Table 3), remission was more likely among participants with a husband who was not working (aOR = 2.04, 95% CI 1.02–4.11 for not working vs. working), lower PHQ-9 score at baseline (aOR = 0.43, 95% CI 0.20–0.90 for score of ≥20 vs. 10–14) and better social support at baseline (aOR = 2.41, 95% CI 1.35–4.31 for high vs. low social support). There was no evidence of a difference in remission by country after adjusting for these factors (p = 0.28). The results from multiple imputation gave similar results (Table 3). There was strong evidence of a greater effect of high social support versus low/moderate support on remission in India than in Pakistan (p = 0.003), and strong evidence of a trend with greater social support in India (p = 0.003) (Appendix 2 of the Supplementary Material).

Table 3. Factors independently associated with remission from depression

Abbreviation: MSPSS, Multidimensional Scale of Perceived Social Support.

1 Adjusted for other variables in the table (country and women’s occupation are included as they are associated with LTFU; month of visit is also adjusted for; other variables are included since p < 0.05 in the multivariable model).

* MI, multiple imputation for missing outcome data (imputed data at 166/854 data points).

** P-value for trend.

Overall, 317 participants had data at both 3- and 6-month time points, and of these 100 (31.6%) had recovery. In multivariable analyses, improved recovery was associated with country (aOR = 1.81, 95% CI 1.02–3.19, p = 0.04 for India vs. Pakistan), and to a lesser extent with better social support (aOR = 2.03, 95% CI 0.84–4.89 for high vs. low social support; p-value for trend = 0.08), higher husband’s education (aOR = 2.22, 95% CI 0.98–5.03; p-value for trend = 0.05) and lower PHQ-9 score (aOR = 0.36, 95% CI 0.10–1.29, p-value for trend = 0.09). Power was relatively lower for this analysis. With 317 participants with data on recovery, we had 80% power to detect a difference in proportions of 25% vs. 40% for variables where 50% of the study population are exposed. Data on recovery are presented in Appendix 3 of the Supplementary Material.

Discussion

To the best of our knowledge, this is the first study which assesses predictors of spontaneous remission and recovery in women with untreated perinatal depression. Almost half the women who did not receive active treatment for perinatal depression had spontaneous remission at 3 or 6 months post birth. Baseline factors associated with remission were lower baseline severity, strong social support from family and friends, and a husband who was not working. Recovery was lower than remission with around a third of women showing spontaneous remission at both 3 and 6 months post birth. Power was lower to detect associations with recovery but there were indications of similar factors as for remission. Remission and recovery were more common in India than in Pakistan in univariable analyses, with evidence of improved remission with greater social support in India.

The finding that participants with lower baseline symptom severity are more likely to remit is similar to research on major depressive disorder (Keller et al., Reference Keller, Lavori, Mueller, Endicott, Coryell, Hirschfeld and Shea1992; Paykel, Reference Paykel1998; Posternak and Miller, Reference Posternak and Miller2001; Rush et al., Reference Rush, Kraemer, Sackeim, Fava, Trivedi, Frank, Ninan, Thase, Gelenberg, Kupfer, Regier, Rosenbaum, Ray and Schatzberg2006). Social support, in the form of instrumental and emotional help has also been identified as an important factor influencing spontaneous remission for depression (Hegel et al., Reference Hegel, Oxman, Hull, Swain and Swick2006; Fuller-Thomson et al., Reference Fuller-Thomson, Battiston, Gadalla and Brennenstuhl2014). Qualitative research further substantiates this finding and confirms that women with depression need a reliable social support system to facilitate the process of natural recovery (Naeem et al., Reference Naeem, Ali, Iqbal, Mubeen and Gul2004). A mother with a husband who is not working was also associated with remission in our analyses. One could speculate that this might infer social support being provided, however, unemployment of the husband may also strain the financial situation of the household and may lead to stress and insecurities in the household. This may aggravate mental health symptoms as seen in other studies (Patel et al., Reference Patel, Rodrigues and DeSouza2002). Therefore, this finding should be interpreted with caution and unpacked further in future studies. Strengths of our study include the size and strong internal validity of the trial procedures (such as no differential drop out, use of adequate control groups, and adherence to research protocols) but our study has also some limitations. First, we were reliant on the baseline variables of the trials and did not have measures of some factors for spontaneous remission and recovery which have been identified for major depressive disorder (Rush et al., Reference Rush, Kraemer, Sackeim, Fava, Trivedi, Frank, Ninan, Thase, Gelenberg, Kupfer, Regier, Rosenbaum, Ray and Schatzberg2006; Fuller-Thomson et al., Reference Fuller-Thomson, Battiston, Gadalla and Brennenstuhl2014). These include the presence of other mental health problems, personality disorders or physical health problems. Whilst we screened for serious mental health problems such as psychosis, and excluded women who needed acute medical help, we did not screen for personality disorders. Personality traits might hinder spontaneous remission, and there is evidence suggesting a negative association between passive dependent personality traits and remission (Paykel, Reference Paykel1998). The type of coping and how to generally deal with life problems may also be important. Problem-focused coping has been shown to promote spontaneous remission, whereas the use of avoidant coping mechanisms may leave people feeling stuck in a specific situation, not allowing them to experience reinforcing activities (Hegel et al., Reference Hegel, Oxman, Hull, Swain and Swick2006).

Second, there may be effects of being enrolled in a trial which may have led to the improvement of symptoms and to spontaneous remission of perinatal depression in our study. Evidence shows that follow-up assessments (Posternak and Zimmerman, Reference Posternak and Zimmerman2007), and informing the patient about their clinical status and illness (Maselko et al., Reference Maselko, Sikander, Turner, Bates, Ahmad, Atif, Baranov, Bhalotra, Bibi, Bibi, Bilal, Biroli, Chung, Gallis, Hagaman, Jamil, LeMasters, O’Donnell, Scherer, Sharif, Waqas, Zaidi, Zulfiqar and Rahman2020) may lead to the improvement of outcomes. This may be explained by the installation of hope, the positive expectation from receiving guidance or therapeutic assessments (Posternak and Miller, Reference Posternak and Miller2001). Other authors (Hengartner, Reference Hengartner2020) substantiate this and explain symptom reduction in depression trials by the Hawthorne effect resulting from receiving any care or additional support such as enhanced usual care. Regression to the mean is another plausible explanation of spontaneous remission and recovery for depression (Hengartner, Reference Hengartner2020) which might have contributed to the high prevalence of remission in our study. Furthermore, we did not conduct clinical interviews with women, but measured symptom severity with the PHQ-9 scale. Symptom scales have been shown to overestimate the prevalence of depression (Thombs et al., Reference Thombs, Kwakkenbos, Levis and Benedetti2018), and may have facilitated the inclusion of women with low baseline severity. For perinatal depression specifically, there have been calls to suggest that the assessment of symptoms lasting 2 weeks may not be sufficient to exclude spontaneous remission without treatment (Scott, Reference Scott1997). Inclusion of a high proportion of moderate cases of perinatal depression (overestimated by the screening tool) may have led in turn to the overestimation of remission rates in our study, given that cases with mild or moderate symptoms are more likely to remit (Whiteford et al., Reference Whiteford, Harris, McKeon, Baxter, Pennell, Barendregt and Wang2013). Third, our definition of spontaneous remission and recovery did not include an assessment of psycho-social functioning and physiological factors (Whiteford et al., Reference Whiteford, Harris, McKeon, Baxter, Pennell, Barendregt and Wang2013) which at times is also considered in the definition of remission and recovery; this may have led to apparent higher remission and recovery rates in our sample.

Conclusion

Women with perinatal depression represent a diverse sub-group, and it is important to identify modifiable factors which may offset symptom trajectories and facilitate the way to recovery. Our study has confirmed that spontaneous remission from depression is a common outcome among mothers. For the first time, we now know that factors such as less severe depression at baseline, and more social support from friends and family are predictive of spontaneous remission. For the purposes of management of depression and the prevention of clinical worsening, these factors can be screened at baseline to help assess treatment prognosis. We were unable to assess relapse of depressive symptoms and if recovery remained stable over the long term. This would have to be investigated in further research, alongside the assessment of relevance of these factors with regards to the specific symptom trajectory women might find themselves in. Future research should also explore the role of social support interventions in the management of perinatal depression.

Open peer review

To view the open peer review materials for this article, please visit http://doi.org/10.1017/gmh.2023.26.

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1017/gmh.2023.26.

Data availability statement

Data from our trials have been made available at the LSHTM data repository available at http://datacompass.lshtm.ac.uk/ (doi: 10.17037/DATA.00000793).

Author contribution

All authors contributed to the study conception and design. D.C.F. conceived the study and H.A.W. and F.V. analysed the data. The first draft of the manuscript was written by D.C.F. and all authors commented on previous versions of the manuscript. All authors read and approved the final version.

Financial support

The research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number 1U19MH095687. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, or the U.S. Department of Health and Human Services. F.V. and H.A.W. were funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is part of the EDCTP2 programme supported by the European Union (Grant No. MR/R010161/1).

Competing interest

The authors declare that they have no competing interest.

Ethics standard

The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. Ethical approval was obtained from the institutional review boards at the London School of Hygiene and Tropical Medicine, Sangath (the implementing institution in India), the Indian Council of Medical Research, the University of Liverpool and the Human Development Research Foundation (the implementing organisation in Pakistan).

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Figure 0

Table 1. Baseline characteristics of participants with untreated perinatal depression

Figure 1

Table 2. Factors associated with remission (PHQ < 5 at 3 or 6 months)

Figure 2

Table 3. Factors independently associated with remission from depression

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Author comment: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R0/PR1

Comments

Dear Dixon Chibanda, dear Judy Bass,

On behalf of the authors, I am submitting a paper entitled “Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan”.

This is the first study which investigates predictors for remission and recovery among a large group of untreated women with perinatal depression, and we analysed data from two completed randomised controlled trials in women with perinatal depression in India and Pakistan.

Analyses were restricted to women in the control groups (who did not receive active treatment). Remission and recovery were measured with the Patient Health Questionnaire-9 (PHQ-9). Remission was defined as PHQ-9<5 at 3 or 6-months post-birth. Recovery was defined as PHQ-9 <5 at both 3- and 6-months post-birth. Generalised estimating equations and logistic regressions were used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for within-person correlation (combining 3- and 6-month data).

The prevalence of remission at 3 months was slightly lower among the 287 participants in Pakistan than the 140 participants in India (44.1% versus 50.8%), with similar results at 6 months (44.7% versus 59.7%). In multivariable analyses, remission was associated with a husband who is not working (adjusted odds ratio, aOR=0.48, 95%CI 0.24-0.97 for working versus not working), lower PHQ-9 score at baseline (aOR=0.43, 95%CI 0.20-0.89 for score of >20 versus 10-14), and better social support at baseline (aOR=2.39, 95%CI 1.32-4.33 for high versus low social support). There was little evidence of an association of any factors with improved recovery.

Our study confirms previous findings for major depressive disorder and shows that baseline severity, and social support from partners and family are important factors which help us understand spontaneous remission of women with perinatal depression. These predictors are important for intervention purposes and for the management of perinatal depression in women with mild or moderate perinatal depression.

We would be delighted if our paper were published in Cambrige Prism: Global Mental Health. Please do not hesitate to get in touch with us if you require further information.

Sincerely, Daniela Fuhr

Prof. Dr. Daniela Fuhr

Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS GmbH

Abt. Prävention und Evaluation

Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH

Department of Prevention and Evaluation

Achterstraße 30

D-28359 Bremen

Tel +49 421 21856 900 (secr.) / 21856 754 (dir.)

Fax +49 421 21856 941

E-Mail: [email protected]

www.leibniz-bips.de

Honorary Professor

London School of Hygiene and Tropical Medicine

Review: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R0/PR2

Conflict of interest statement

Reviewer declares none.

Comments

The authors examine factors associated with remission of perinatal depression in the absence of treatment. Control arms of RCTs conducted in India and Pakistan were used for this analysis. The topic as well as the setting underscores the importance of the study. Please see my comments below:

1. Throughout the manuscript, a number of sentences are very long involving “and” and “but”, sometimes multiple times within the same sentence. I recommend splitting those sentences up for more clarity and ease of reading.

2. Last sentence of page 2. “Although .....” is one such sentence. In addition, I am not sure if it is necessary to state, “the predictors of spontaneous remission and recovery <b>among women with untreated perinatal depression..</b>.” Doesn’t “spontaneous remission” automatically imply that the women received no treatment? It may be helpful to provide some kind of a definition for spontaneous remission at the start of this paragraph, even if that definition applies only in the context of this study.

4. Methods (page 4, line 120-121): please elaborate on “without outcome data”. Does this mean only those who had information for both 3 and 6-months follow up were included in the final analyses?

5. Please specify when (which year[s]) the trials were conducted.

6. Results, lines 151-154: how were moderate and severe depression defined? How was social support measured?

7. Given that the prevalence of remissions (lines 166-170) was statistically significantly different, it may be better to refrain from using “slightly” [line 166] and rather let the readers draw their own conclusions.

8. Lines 177-179: I think it makes more sense to follow the same “order” when presenting the adjusted OR’s within parentheses. For instance, having a husband who wasn’t working increased the likelihood of remission. Thus, it would be more intuitive to see the odds of remission for those with husbands not working vs working (the aOR within parentheses would be higher than 1), rather than the inverse.

9. Were the PHQ-9’s translated into local languages and were those already validated in local languages?

10. In this paper, it appears that husband not working is being used aas a surrogate measure for the level of support the woman may have at home. Is there evidence from elsewhere to support that? How might that interact with the financial stability of the household, in terms of their effect on perinatal depression?

11. I am wondering what was the P value cut off used to determine the variables for multivariable model? If it was 0.1, then based on table 2, other variables (such as husband level of education, domestic violence) deserve to be included. If it was 0.05, husband occupation need not be included. The limited description in methods does not make this clear.

Review: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R0/PR3

Conflict of interest statement

I’m sorry but I didn’t realize this initially that one of the co-authors on this manuscript is someone I work with very closely.

Comments

The current manuscript explores the predictors of remission of depression symptoms in the first 6 months post-partum among a control arm of a depression trial in India and Pakistan. The analysis is possible due to the relatively weak enhanced usual care received in this group and so this approach is unique. Below I outline a few changes that I believe would significantly improve the manuscript.

Sentence starting at line 40 in the introduction, what do the percentages refer to?

The methods section is missing details introducing the variables and measures/scales used in the analyses. For example, how was financial empowerment or domestic violence measured? This can also help avoid some confusion in table 1 where number of children is presented earlier in the table, while later there is information on parity and miscarriages.

It is not clear how the specific potential predictors of remission/recovery were chosen for consideration to be included in the model (besides country). Does the list reflect the full set of variables that were available at both locations?

In line 138, please clarify what is meant by 118,260 women being assessed for eligibility, what was the process? The initial numbers are drastically different between India and Pakistan, suggesting a different recruitment strategy.

On line 146, the comparison of education could be made much clearer by either stating ‘fewer than secondary’ or acknowledging the bimodal difference in that, in Pakistan, a higher proportion of women either had no education or had higher levels of education than in India.

Please define what does ‘combining data from both 3 and 6 months’ mean in the analyses– is it remission at either 3 or 6 months?

Starting on line 177, the text presents the table 3 results in a confusing way, presenting the flip of the presented regression results. It would be easier for the reader to state, for example, that husband working and higher phq-9 scores were associated with a lower odds of remission, while higher social support was associated with greater odds of remission.

The paragraph on recovery is presented more like an after-thought. For example, no information is given about the significantly reduced sample size. These results would seem more important to present than, for example, the MI results which are currently in table 3. This is especially so given that the results on recovery are important enough to be summarized in the first paragraph of the discussion. On the other hand, the authors do not return to a discussion about how there do not seem to be any strong predictors of recovery, which seems like a lost opportunity.

The first paragraph of the discussion mentions adjustment for confounders but the analysis does not appear to be driven at all by concerns of confounding and/or causality.

The discussion misses several opportunities to elaborate on the potential reasons underlying the findings – especially things like husband working (i.e. what does this mean in terms of SES?), and the fact that the strong initial predictive value of country seems to weaken in the final model.

Recommendation: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R0/PR4

Comments

Dear authors,

This study is of interest to reader of this journal.Howerver, both reviewers raised significant concerns about the conceptual frame work, methods of the study and the quality of the writing. Nevertheless, I am willing to give you the opportunity to revise your paper and respond to each of their comments.

Decision: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R0/PR5

Comments

No accompanying comment.

Author comment: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R1/PR6

Comments

No accompanying comment.

Review: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R1/PR7

Conflict of interest statement

Reviewer declares none.

Comments

Based on the authors' responses, I believe my concerns to the initial draft have been addressed. I have no further comments.

Review: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R1/PR8

Conflict of interest statement

Reviewer declares none.

Comments

all of my comments have been addressed

Recommendation: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R1/PR9

Comments

No accompanying comment.

Decision: Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan — R1/PR10

Comments

No accompanying comment.