Giving birth to a baby is undoubtedly a major event in a person’s life. The arrival of a tiny human (not to be confused with an elf; same size but different needs) will impact a family in a multitude of ways. While the addition of the new family member is positive and joyous for many, this is unfortunately not the case for everyone (Märthesheimer S. et al., 2025).
One in nine mothers experience postpartum depression (PPD) (Bai Y. et al., 2023). It is characterised by a persistently low mood or a loss of interest in previously enjoyed activities, and is often accompanied by other symptoms, such as disturbed sleep, slowed movement or a decline in cognitive abilities. PPD can have serious consequences for both parent and child, affecting daily functioning and quality of life (World Health Organisation, 2025).
Many different treatments exist for PPD, including both non-pharmacological approaches such as psychotherapy, music therapy, or exercise, and pharmacological ones like antidepressants or hormones (Guan L. et al., 2025). However, treatment is not effective for all parents with postpartum depression. To better understand this subgroup of mothers with difficult-to-treat postpartum depression, Chen and colleagues (2026) worked to identify key risk factors associated with failed treatment.
Not all parents experience the postnatal period as joyful, with around one in nine mothers developing postpartum depression.
Methods
Using data from several nationwide public healthcare Swedish databases, Chen and colleagues identified common characteristics of mothers with difficult-to-treat postpartum depression.
PPD was defined as the first depression diagnosis in specialist or primary care, or first antidepressant prescription, during the first year after childbirth. ‘Treatment-resistance’ was defined by the authors as the use of three or more antidepressants, any add-on medication recommended for difficult-to-treat depression, or electroconvulsive therapy (ECT) or transcranial magnetic stimulation (rTMS) within one year of childbirth.
Adjusted risk ratios (RR) were calculated for different patient characteristics (e.g., sociodemographics, lifestyle, pre-existing medical factors) to identify risk factors associated with PPD treatment resistance. Sensitivity analyses were then conducted to test the robustness of results using alternative definitions of treatment resistance, restricting to clinically confirmed PPD or including primary care data only.
Results
The researchers identified 58,618 women with PPD in the Swedish health care system between the years of 2006 to 2021. Within one year of their respective diagnoses, 6% (n = 3,522) experienced treatment resistance. Among them, most (86.5%) received some form of treatment (antidepressants, add-on medications, ECT, or rTMS). Several risk factors associated with treatment-resistance emerged:
Sociodemographics
Women with PPD were at a higher risk of experiencing treatment resistance if they were:
- Born in a European country other than Sweden: RR = 1.25
- Born outside of Europe: RR = 1.15
- Living in the northern half of Sweden: RR = 1.17
- Living alone: RR = 1.27
- Of a lower educational status (<9 vs >12 years): RR = 1.61
- Of a low household income (lowest 20 % vs. top 20 %): RR = 1.35
- Diagnosed prior to 2015: RR = 0.85
- Smokers in early pregnancy:
- 1-9 cigarettes/day RR = 1.45;
- ≥10 cigarettes/day RR = 1.53.
Physical and psychiatric conditions
The presence of pre-existing chronic physical conditions increased the risk of difficult-to-treat PPD, but this varied depending on both amount and type of illness (Charlson comorbidity index: 1 condition, RR = 1.28; ≥2 conditions, RR = 1.42).
Similarly, pre-existing mental health conditions were connected to an increased risk (any psychiatric disorder: RR = 2.21), ranging from 1.69 for women with substance use disorders and up to 8.49 for psychotic disorders.
Pregnancy and birth
‘Treatment-resistance’ was more likely after preterm birth (32-36 weeks: RR = 1.23) or after caesarean section (RR = 1.15), while three or more births also increased risk.
Other pregnancy outcomes such as multiple gestation or infant health measures did not emerge as significant risk factors.
Sensitivity analyses
Associations were broadly consistent when analyses were limited to women without prior psychiatric disorders, to clinically confirmed PPD cases, or to counties with primary care data. Using alternative definitions of ‘treatment-resistance’ and mutually adjusted models also yielded similar results.
Difficult-to-treat postpartum depression was more common in women with prior health conditions, lower education or income, smoking history in early pregnancy, or following caesarean or preterm birth.
Conclusions
Using nationwide data from the Swedish health care data, the authors found that approximately 6% of women with PPD experience ‘treatment-resistance’ within one year of their first diagnosis. The authors concluded that increased risk of treatment resistance is faced by:
primiparous patients [someone who has given birth only once or is giving birth for the first time] with lower socioeconomic status, cigarette smoking and pre-existing physical and psychiatric conditions.
About six percent of women with postpartum depression develop treatment resistance within a year, highlighting the need for early monitoring and targeted support.
Strengths and limitations
The authors used nationwide databases managed by the Swedish health care system, which is publicly funded and therefore accessible to the entire population. Chen and colleagues were thereby able to use widespread data for a large sample size of almost 60,000 women, considered representative for the Swedish population. This reduces the risk of biases that might be introduced during the recruiting process. Any remaining confounding factors were addressed in the extensive sensitivity analyses where possible.
It could be that classifying women who use antidepressant medication as having depression without a professional diagnosis included women prescribed antidepressants for other conditions. The researchers therefore calculated risk factors using only data from women who were diagnosed by their primary care physicians and compared these results to those from the whole sample. As the risk factors remained the same, it can be said that a wider interpretation of PPD diagnosis did not distort the results. The same was applied for other definitions of treatment resistance, strengthening the validity of the identified risk factors.
Still, the study has limitations. A key one is that all applied definitions of ‘treatment-resistance’ focused heavily on pharmaceutical treatment. This neglects women who decided against using medication, or against trying a second or third type of medication after the first one failed. This definition implies that stopping medication means the treatment was successful, but other explanations are possible. For example, moving out of the country, or stopping treatment due to lack of positive effect. This definition also does not address use of or resistance to other treatment methods, such as psychotherapy, even though psychotherapy is a recommended treatment for PPD (National Institute for Health and Care Excellence, 2020).
You can read more on psychotherapy and postpartum depression in these articles by the Mental Elf: “Culturally adapted CBT may lead to recovery from postnatal depression” (Tong A., 2025) and “Cost-effective therapy for postnatal depression in British South Asian Mothers” (Staines L., 2025).
The study’s use of nationwide registers strengthens the findings, but ‘treatment-resistance’ definitions focus on medication and do not capture other therapies or personal treatment choices.
Implications for practice
The named risk factors encompass lifestyle aspects, socioeconomic factors and other health conditions, and so translating the results into practice will require collaboration between professionals from all of these areas. This will be challenging, but could greatly benefit new parents worldwide.
All of the identified fisk factors are already well understood to be major stressors that can negatively impact mental health (Dougall I. et al., 2024; Huang Y. et al., 2023). The cumulation of such stress in addition to the physiological demands of childbirth and caring for a newborn, starts a cascade of changes in the mother’s body (Agorastos A. & Chrousos G., 2022). This new research by Chen and colleagues shows that these stressors are also linked to higher risk of difficult-to-treat PPD. While this may be unsurprising, gathering evidence at a population level is an important step.
By identifying risk factors for ‘treatment resistance’, Chen and colleagues provide important groundwork for more personalised care. Assessing a patient’s risk of developing difficult-to-treat PPD could allow targeted preventative measures to be implemented before ‘treatment-resistance’ develops. Even though such interventions still need to be designed, evaluated and eventually integrated into standard care, understanding more about the risk factors involved helps lay the foundation in this process. In the long run, this approach could bring postpartum health care closer to the goal of successfully treating all parents with PPD so that they too may experience the joy of the arrival of their new elf-like family member.
Understanding risk factors for difficult-to-treat postpartum depression lays the groundwork for targeted prevention and more personalised care for new parents.
Statement of interests
Hannah Bielefeld has no conflicts of interests and reports no use of AI in her writing or editing of this blog.
Editor
Edited by Éimear Foley. AI tools assisted with language refinement and formatting during the editorial phase.
Links
Primary paper
Chen, Yufeng, Bränn, Emma, Bendix, Marie, Joyce, Emily E., Fransson, Emma, Lu, Yi, Skalkidou, Alkistis, & Lu, Donghao (2026). Risk factors for treatment resistance among women with postpartum depression in a nationwide study. Nature Mental Health, 4(2), 288–297. https://doi.org/10.1038/s44220-026-00587-8
Other references
Agorastos, A., & Chrousos, G. P. (2022). The neuroendocrinology of stress: The stress-related continuum of chronic disease development. Molecular Psychiatry 2022, 27(1), 502–513. https://doi.org/10.1038/s41380-021-01224-9
Bai, Y., Li, Q., Cheng, K. K., Caine, E. D., Tong, Y., Wu, X., & Gong, W. (2023). Prevalence of Postpartum Depression Based on Diagnostic Interviews: A Systematic Review and Meta-Analysis. Depression and Anxiety 2023, 2023(1), 8403222. https://doi.org/10.1155/2023/8403222
Dougall, I., Vasiljevic, M., Wright, J. D., & Weick, M. (2024). How, when, and why is social class linked to mental health and wellbeing? A systematic meta-review. Social Science & Medicine 2024, 343, 116542. https://doi.org/10.1016/j.socscimed.2023.116542
Guan, L.-N., Li, L., Li, H.-H., Wang, Z., Yun, J.-J., Ding, W.-F., Sun, G.-Y., & Xue, L. (2025). Research Progress in the Treatment of Postpartum Depression. Cellular and Molecular Neurobiology 2025, 45(1), 35. https://doi.org/10.1007/s10571-025-01542-4
Huang, Y., Loux, T., Huang, X., & Feng, X. (2023). The relationship between chronic diseases and mental health: A cross-sectional study 2023. Mental Health & Prevention, 32, 200307. https://doi.org/10.1016/j.mhp.2023.200307
Märthesheimer, S., Hagenbeck, C., Helbig, M., Balan, P., Fehm, T., & Schaal, N. K. (2025). A longitudinal study of the subjective birth experience and the relationship to mental health. BMC Pregnancy and Childbirth 2025, 25(1), 216. https://doi.org/10.1186/s12884-025-07348-y
National Institute for Health and Care Excellence. (2020, February 11). Recommendations | Antenatal and postnatal mental health: Clinical management and service guidance. NICE. Guidance | NICE. https://www.nice.org.uk/guidance/cg192/chapter/recommendations#treating-specific-mental-health-problems-in-pregnancy-and-the-postnatal-period
Staines, L. (2025, April 24). Cost-effective therapy for postnatal depression in British South Asian Mothers. National Elf Service.
Tong, A. (2025, April 23). Culturally adapted CBT may lead to recovery from postnatal depression. National Elf Service.
World Health Organisation. (2025). International Classification of Diseases Eleventh Revision (ICD-11).
