Epidemiology, pathophysiology, and interventions for postpartum depression: Systematic review

Table 1 Risk factors for postpartum depression graded by strength of evidence

Evidence level	Risk factors (≥ 2 high-quality SRs/> 1 000-case cohorts)	Representative evidence & effect size
High	Previous major depression; Antenatal (pregnancy) anxiety; Family history of psychiatric disorders	OR ≈ 7.3 for prior depression[12]; OR = 2.09 for family history[13]
Medium	Caesarean birth, especially emergency CS (EMCS OR ≈ 1.18); 25(OH)-vitamin D deficiency (OR ≈ 1.4-1.8 in RCTs)	OR = 1.18 in pooled meta-analysis[14]; Systematic review of RCTs[15]
Low	Single social-stress event; Low income with adequate social support	No consistent pooled effect; evidence limited to small cross-sectional or non-replicated studies[16]

Correlation coefficients (r) reported in some meta-analyses were converted to odds ratios (OR) for consistency using the formula OR ≈ exp (π·r/√3). CS: Caesarean section; EMCS: Emergency caesarean section; aOR: Adjusted odds ratio; OR: Odds ratio; 25(OH)-vit D: 25-hydroxy-vitamin D; SR: Systematic review; RCT: Randomized controlled trial.

Table 2 Evidencebased intervention modalities for postpartum depression

Modality	Core elements	Key evidence (illustrative)	Target population	Evidence grade
Drug	Brexanolone 60 hours IV; zuranolone 14 days oral; conventional SSRIs	Brexanolone phaseIII (n = 246): Mean ΔPHQ19 = -17.0 (95%CI: -19.3 to -14.7) within brexanolone arm, -14.5 vs placebo; zuranolone phaseII: Rapid onset	Moderatetosevere PPD; lactating mothers with careful evaluation	IA
Psychological/psychotherapy	CBT (facetoface/online); IPT (partner/group); MBCT	CBT metaanalysis 2022 (31 RCTs) SMD -0.62; coupleIPT RCT ΔEPDS -4.1; MBCTPD trial: 50% relapserisk reduction	Mildtomoderate PPD or women declining drugs	IA
Exercise/lifestyle	≥ 150 minutes per week moderate aerobic exercise; highfiber diet; vitaminD supplementation	Systematic review 2022 (35 studies) RR 0.77; highfiber diet improves gut microbiota & mood	Women ≥ 6 weeks postpartum who are physically able	IB
Integrated/community	CHW “Thinking Healthy” module; digital appbased CBT; WHO mhGAP + group IPT	WHO mhGAP + nurseled groupIPT RCT in Nepal: ΔEPDS -4.3	Resourcelimited or lowaccess settings	II
Neuromodulation (pilot/protocol)	Anodal prefrontal tDCS 2 mA × 20 minutes, 10 sessions	Protocol only: Sun et al[52], 2023 RCT design; planned n = 120, primary outcome ΔEPDS at 4 weeks	Moderate PPD unresponsive to CBT/SSRI	NR

Evidence grade (adapted from GRADE and USPSTF criteria): IA = High-certainty evidence from ≥ 1 multicenter Phase III RCT or ≥ 2 consistent meta-analyses; IB = Moderate-certainty evidence from ≥ 3 independent RCTs or large single-site trials; II = Low- to moderate-certainty evidence from single-center or quasi-experimental designs, pilot RCTs, or implementation studies. NR: Not yet rated; evidence limited to pilot studies or published protocols (no completed RCT with clinical outcomes). RCT: Randomized controlled trial; PHQ: Patient Health Questionnaire; EPDS: Edinburgh Postnatal Depression Scale; CBT: Cognitive behavioral therapy; tDCS: Transcranial direct current stimulation; CHW: Community health worker; WHO: World Health Organization; PPD: Postpartum depression; EPDS: Edinburgh Postnatal Depression Scale.