Are interventions effective in preventing PPD among women from the general population, non-depressed, with no known risks or not identified as at risk for developing PPD?

The effectiveness of several interventions was examined: psychological and psychosocial interventions, antidepressant medication, dietary supplements and physical activity. Pregnant and postpartum women identified as at risk for developing PPD should receive psychological and psychosocial interventions for the prevention of PPD. Pregnant and postpartum women with no known risks for developing PPD could benefit from receiving psychological and psychosocial interventions for the prevention of PPD. Associated with efficacy studies, cost measures such as maternal/parental outcomes (e.g. morbidity, health-related quality of life, health services use, return to work), infant/child outcomes (e.g. preterm birth, infant mortality, vaccination, neurodevelopmental, socio-emotional and behavioural problems, school performance) and parenting outcomes (e.g. maltreatment of children and intimate partner violence (IPV)) should determine whether such types of interventions are worthwhile to implement (Table 1). Some recommended types of such preventive interventions for women at risk and women with no known risks include interventions based on cognitive–behavioural therapy (CBT) and interpersonal therapy (IPT), postpartum professional-based home visits, midwifery redesigned postnatal care and postpartum lay-based telephone support. ^{Reference Dennis and Dowswell16–Reference O’Connor, Senger, Henninger, Coppola and Gaynes18}

Table 1 Summary of recommendations for prevention of peripartum depression (PPD)

Note: Levels of recommendation: strong/weak/no recommendation; levels of evidence: ++++ high, +++ moderate, ++ low, + very low.

Pregnant and postpartum women with subclinical PPD symptoms could benefit from psychological and psychosocial interventions for the prevention of PPD. Some recommended types of such interventions include interventions based on CBT and IPT and parent–infant interaction treatment. ^{Reference Morrell, Sutcliffe, Booth, Stevens, Scope and Stevenson17}

Concerning pharmacological intervention to prevent PPD, there is one Cochrane review that investigated if antidepressant initiation after delivery could prevent PPD. The review includes two randomised controlled trial (RCT) studies with 73 women. The relative risk for postpartum depression was 0.14 (95% CI: 0.02–1.07, p = 0.058) in the sertraline arm versus placebo, but there was no difference between nortriptyline and the placebo group. Because of low statistical power and scarce evidence, a conclusion on the effectiveness of antidepressants in the prevention of PPD cannot be made.

There is no available evidence about the efficacy of antidepressant initiation during pregnancy for prevention of depression during pregnancy. There is limited evidence to recommend that dietary intake influences the risk of PPD. ^{Reference O’Connor, Senger, Henninger, Coppola and Gaynes18–Reference Suradom, Suttajit, Oonarom, Maneeton and Srisurapanont20}

Pregnant and postpartum women could benefit from physical activity for the prevention of PPD. Some recommended types of physical activity include stretching, Pilates and aerobics. In addition, at least 90 min of physical activity per week are recommended for prevention of PPD. ^{Reference O’Connor, Senger, Henninger, Coppola and Gaynes18,Reference Yuan, Chen, Chen, Wan, Luo and Zhang21}

Are screening programmes effective in detecting the presence of risk factors for vulnerability to depression?

We specifically examined whether screening programmes were effective in detecting the presence of risk factors for vulnerability to depression. For this question, we identified two systematic reviews: Felice et al ^{Reference Felice, Agius, Sultana, Felice and Calleja-Agius26} focused on four RCTs on pregnant women screened by a psychosocial assessment tool, for example, ALPHA or ANRQ, including known risk factors for PPD. When compared to routine care, psychosocial assessments were found to be sensitive to detect risk factors associated with postpartum depression. Results from three studies reported no statistically significant differences in postpartum depression. One study did not report on depression outcomes. One study found higher referral rates to social services in the intervention group, while another showed higher social support postpartum. The level of evidence varied.

In the systematic review on screening for IPV by Feltner et al, ^{Reference Feltner, Wallace, Berkman, Kistler, Middleton and Barclay27} five studies focusing on IPV screening among peripartum women showed lower IPV rates postpartum in the screening group. Fewer postpartum depressive symptoms in the intervention group were reported in some studies. It is important to note that evidence based solely on systematic reviews was scarce in this area. Further research to assess efficacy, feasibility, acceptability, preferences and cost-effectiveness of such high-risk assessment programmes is warranted.

Psychological treatment of PPD

Are psychological interventions effective in treating PPD?

We identified 15 systematic reviews. ^{Reference Huang, Zhao, Qiang and Fan28–Reference Zhao, Chen, Lan, Deng, Liao and Yue42} Fourteen were consistent in showing that psychological interventions were effective in treating depressive symptoms during pregnancy and postpartum compared to no treatment (Table 3). With respect to different psychological approaches, the evidence is strongly related to CBT. The evidence for effectiveness of CBT’s third-wave techniques (behavioural activation, mindfulness-based techniques and acceptance-commitment therapy (ACT)) was weak. Furthermore, the evidence of IPT effectiveness was also weak. In summary, psychological treatments, especially CBT, are effective in treating PPD and should be used.

Table 3 Summary of recommendations for psychological treatment of peripartum depression

Note: Levels of recommendation: strong/weak/no recommendation; levels of evidence: ++++ high, +++ moderate, ++ low, + very low.

Pharmacological treatment of PPD

Are pharmacological interventions effective in treating PPD?

With regards to the effectiveness of antidepressant medication in PPD, the evidence is limited as double-blinded placebo-controlled randomised drug trials are difficult to conduct in pregnant and breastfeeding women because of ethical considerations. However, a Cochrane review ^{Reference Brown, Wilson and Ayre43} showed superiority of antidepressant medication compared to placebo especially in women with moderate-to-severe depression. There are numerous meta-analysis and systematic reviews investigating the safety of antidepressant medication use in pregnancy with regards to malformation risk and other outcomes in exposed children. The evidence is quite strong that antidepressants in general are not major teratogens. In different drugs, there were hints of a mildly increased malformation risk, but the causality is not clear and rather doubtful. However, there is sufficient evidence that untreated depression can have negative impacts on exposed children; ^{Reference Mitchell and Goodman44} therefore, the risk of not treating depression should always be discussed and weighed against potential effects of the medication.

Discontinuation of existing antidepressant treatment is not recommended in women with a history of severe and recurrent disorder because of increased risk of relapse. ^{Reference Lupattelli, Corrao, Gatti, Rea, Trinh and Cantarutti45} However, to reduce potential negative effects of the medication, women should be treated with monotherapy and the lowest effective dose, if possible. Regular therapeutic drug measurements (TDMs), that is, measurement of the antidepressant blood concentration at designated time intervals, can be helpful in achieving those goals of optimal dosing, as there is evidence of changes in pharmacokinetics during the three trimesters of pregnancy. ^{Reference Schoretsanitis, Spigset, Stingl, Deligiannidis, Paulzen and Westin46} As clinicians and affected individuals are often reluctant to increase dosages in pregnancy even if depressive symptoms are not sufficiently controlled, TDM can support informed shared decision-making. However, prospective studies to investigate if TDM in pregnancy leads also to an improvement in clinical outcome are still lacking. As most likely the depression of the mother alone increases the risk for pregnancy and birth complications, affected women should give birth in hospitals with specialised neonatal care units. ^{Reference Rommel, Semark, Liu, Madsen, Agerbo and Munk-Olsen47}

The Food and Drug Administration (FDA) has licensed the first specific medication for PPD treatment, the neurosteroid brexanolone. The evidence of two meta-analyses shows that brexanolone is more effective than placebo and more rapidly acting than selective serotonin reuptake inhibitors (SSRIs) in treating PPD. ^{Reference Zheng, Cai, Zheng, Sim, Ungvari and Peng48,Reference Cooper, Kilvert, Hodgkins, Roskell and Eldar-Lissai49} To date, there is no evidence that specific antidepressants would be more effective in women in pregnancy and/or postpartum.

In summary, antidepressant medication should always be prescribed after careful assessment of the individual risk–benefit ratio, including previous history, current severity of symptoms, patients’ preference and availability of alternative treatments (Table 4).

Table 4 Summary of recommendations for pharmacological treatment of peripartum depression

GPP, good practice point.

Note: Levels of recommendation: strong/weak/no recommendation; levels of evidence: ++++ high, +++ moderate, ++ low, + very low.

Are non-invasive brain stimulation (NIBS) interventions effective in reducing depressive symptoms during pregnancy and in the postpartum period pre–post treatment or when compared with other intervention or no intervention?

Although the evidence for repetitive transcranial magnetic stimulation (rTMS) is promising, the literature shows very low to low evidence of effectiveness both as a stand-alone and coadjuvant treatment with pharmacotherapy in reducing PPD symptoms during pregnancy and postpartum. The low level of evidence is caused by the weak design of the clinical studies and the lack of adequately powered RCTs. ^{Reference Cole, Bright, Gagnon and McGirr50–Reference Peng, Zhou, Xue, Bai, Yu and Li54}

During pregnancy, only half of the studies showed rTMS efficacy as an adjunctive treatment to medication in pre- to post-intervention analysis; response and remission rates ranged between 38.8% and 81.8% and 18.8% and 61.1%, respectively. However, this effect was not significantly different compared to sham control groups. ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53}

In the postpartum period, rTMS efficacy results are promising. Hence, despite the heterogeneity of treatment protocols, the evidence is of higher quality with optimal information size and large effect sizes (standardised mean difference (SMD) = −1.02 (95% CI [−1.37 to −0.66], I ² = 83%). ^{Reference Peng, Zhou, Xue, Bai, Yu and Li54}

Evidence on adverse effects for the foetus during pregnancy show no association with the intervention and, for the women, adverse effects reported were equivalent to those found in the general population. ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53} Considering the literature on the safety profile of rTMS in the general population, ^{Reference Bikson, Ganho-Ávila and Datta56} severe adverse effects are unlikely in the postpartum stage.

Acceptability and feasibility data suggest women’s openness to treatment both during pregnancy and postpartum, ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53,Reference Peng, Zhou, Xue, Bai, Yu and Li54,Reference Kim, Wang, McGeehan, Snell, Ewing and Iannelli57} particularly when using shorter protocols such as theta burst stimulation.

Although the evidence for rTMS is still scarce for PPD, considering the effectiveness on depressive symptoms in the general population and the safety profile, our recommendations consider that if rTMS is accessible and available, it can be an alternative treatment for pregnant or postpartum women with mild-to-moderate depressive symptoms, according to their clinical condition, values and preferences.

There is some evidence showing the benefit of tES as a stand-alone or coadjuvant with psychotherapy in improving depressive symptoms during pregnancy. Within tES, tDCS is the most studied strategy, showing a highly tolerable and safe profile for women and the foetus. Surprisingly, in the postpartum period, there is only one case report available in the literature showing a positive effect of tDCS to improve depressive symptoms. Therefore, despite tDCS’s benign effects in the general population, there is not enough data to make a recommendation on the use of tES postpartum.

Because of ethical concerns, the literature on the efficacy of ECT in PPD during pregnancy is of low quality, with no RCTs available, relying only on case series and case studies. ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53,Reference Calaway, Coshal, Jones, Coverdale and Livingston58,Reference Leiknes, Cooke, Jarosch-von Schweder, Harboe and Høie59} All articles report patients with severe PPD, presenting life-threatening conditions.

Adverse effects on the mother were reported in about 27–52.4% of patients and include vaginal bleeding, uterine contractions, abdominal and pelvic pain, miscarriage, preeclampsia and premature birth and spontaneous abortion when the treatment was delivered during the first trimester. ^{Reference Calaway, Coshal, Jones, Coverdale and Livingston58–Reference Pompili, Dominici, Giordano, Longo, Serafini and Lester60} Caesarean, premature labour and uterine contractions associated with treatment are the most common obstetric complications associated with ECT treatments delivered in later semesters. ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53} Moreover, neurocognitive assessment after ECT extracted from one single study ^{Reference Salzbrenner, Breeden, Jarvis and Rodriguez61} suggests that the maximum number of ECT sessions before achieving cognitive decline should be nine.

Rates ranging between 27.7% and 57.1% of significant adverse outcomes to the foetus and the child are also reported. These figures warrant strict supervision of ECT during pregnancy, which should be held preferably in a hospital setting by experienced healthcare teams.

The literature on using ECT in the postpartum ^{Reference Pacheco, Guiomar, Brunoni, Buhagiar, Evagorou and Roca-Lecumberri53,Reference Gressier, Rotenberg, Cazas and Hardy62} encompasses case reports and retrospective and observational studies, observing postpartum women in the context of severe psychiatric disorders, unresponsive to other treatments. A percentage of 28% of adverse events was reported and remission rates were between 76.9% and 92%.

Therefore, despite the potential for serious adverse effects and complications, particularly during pregnancy and delivery, the benefits of ECT seen in the clinical practice often outweigh these risks in urgent, life-threatening situations where conventional treatments have failed. While the GDG recognises the very low level of evidence, we acknowledge the clinical experience of our experts, strongly recommending ECT where it can be a lifesaving intervention, which is the case with life-threatening, therapy-resistant severe perinatal depression (PPD). Note, however, that ECT treatments, particularly during pregnancy, should be held in hospital settings close to a labour ward, by experienced healthcare teams including an obstetrician, and warranting strict supervision, including cardiotocography monitoring.

Finally, the literature on the efficacy of BLT in reducing depressive symptoms in pregnant women ^{Reference Dennis and Dowswell16,Reference Nillni, Mehralizade, Mayer and Milanovic36,Reference Al-Karawi and Jubair63–Reference Smith, Shewamene, Galbally, Schmied and Dahlen65} reports inconsistent findings and the quality of the evidence is very low given the reduced number of women and the moderate risk of bias of the studies. As for BLT postpartum, only one study is available observing the effect of improving depressive symptoms in postpartum women. Therefore, there is no evidence on the efficacy of BLT that allows us to provide recommendations either during pregnancy or the postpartum period.

Are CATs effective in reducing depressive symptoms during pregnancy and in the postpartum period pre–post treatment or when compared with other interventions or no intervention?

Overall, the quality of the current evidence about the effectiveness of fatty acids in reducing depressive symptoms in pregnant and postpartum women is low to moderate, given its inconsistency and risk of bias. However, the direction of findings suggests their potential effect in mild-to-moderate depressive symptoms, when compared to placebo, but not in severe symptoms. Adverse effects associated with fatty acids are likely to be trivial. ^{Reference Dennis and Dowswell66–Reference Zhang, Zou, Li, Wang, Sun and Shi69}

Physical exercise for pregnant women with depressive symptoms encompasses low-to-moderate or moderate-to-vigorous dancing, walking, aerobic exercise, stretching and relaxation. Although the available literature on the efficacy of physical exercise on depressive symptoms during pregnancy is of low quality, it shows a beneficial effect. ^{Reference Lin, Huang, Chou and Shih72} Furthermore, whereas adverse effects of exercise interventions in pregnancy are absent for healthy pregnant women, physical exercise is counter indicated in pregnant women with several health conditions. The American College of Obstetricians and Gynecologists (ACOG) advises against aerobic exercise for pregnant women with certain conditions, such as hemodynamically significant heart disease, restrictive lung disease, incompetent cervix/cerclage, risk of premature labour in multiple gestations, persistent bleeding in the second or third trimester, placenta praevia, ruptured membranes and pregnancy-induced hypertension. In addition, the ACOG ¹¹ suggests that aerobic exercise may be inappropriate for pregnant women with severe anaemia, unassessed maternal cardiac arrhythmia, chronic bronchitis, extreme obesity, very low body weight (body mass index <12), lack of physical activity, intrauterine growth restriction, uncontrolled hypertension/preeclampsia, orthopaedic limitations, uncontrolled type II diabetes, seizure disorders, thyroid disease and a history of significant cigarette smoking. The ACOG also highlights specific warning signs, such as vaginal bleeding, shortness of breath before exertion, dizziness, headache, chest pain, muscle weakness, calf pain or swelling (which may indicate thrombophlebitis), signs of preterm labour, reduced foetal movement and leakage of amniotic fluid, which should prompt the immediate cessation of exercise. ^{Reference Shivakumar, Brandon, Snell, Santiago-Muñoz, Johnson and Trivedi71}

In the postpartum period, physical exercise (group or individual aerobic, walking and pram walking, whole-body stretching sessions; in-person or through e-health systems) seems to be of benefit in reducing depressive symptoms. However, the heterogeneity of exercise interventions described in the literature results in some degree of uncertainty about the parameters for optimal results.

Despite the low quality of the evidence, the literature shows that yoga might be beneficial to improve depressive symptoms during pregnancy in physically healthy women ^{Reference Liu, Huang, Hu and Wang33,Reference Lin, Huang, Chou and Shih72} with unlikely associated risks for the foetus/newborn. This recommendation is cautious, as the literature is unclear regarding symptoms’ severity and is based on low-quality evidence. In the postpartum period there is no evidence of the efficacy of yoga to improve depressive symptoms. ^{Reference Liu, Huang, Hu and Wang33,Reference Jiang, Xu, Li, Deng, Peng and Ruan73,Reference Wang, Liang and Sun74}

Although the literature is of low quality, massage might be beneficial to improve depressive symptoms during pregnancy ^{Reference Zhu, Wang, Tang, Li, Xu and Zhang70} when it is applied by partners or therapists. Given there are currently no studies on the effect of massage in the postpartum period, no recommendation is possible.

To date, there is only one study observing the effects of peer support in PPD during pregnancy and therefore a recommendation is not possible. Postpartum, interventions are recommended to be provided by health professionals (mediators) or trained peers who have similarities to the pregnant women and have personal experience of previous PPD. No adverse effects are expected, and rates of satisfaction are expected to be high. Interventions can be delivered individually or in a group, or a combination of the two, and those that are technology-based seem to be more consistent. However, while technology increases accessibility it might also increase inequality with those who do not have the resources or the willingness to use digital alternatives. ^{Reference Fang, Lin and Chen75,Reference Zhou, Hu, Wang, Zhu, Feng and Xue76}

The available literature on the use of acupuncture for PPD is inconsistent. ^{Reference Nillni, Mehralizade, Mayer and Milanovic36,Reference Van Ravesteyn, Lambregtse-van den Berg, Hoogendijk and Kamperman64} Moreover, electro-acupuncture shows transient adverse effects. ^{Reference Yang, Di, Shergis, Li, Zhang and Lu77} No recommendation for the use of acupuncture is possible at the current stage.

There is no current literature available on the effect of Chinese herbs in reducing depressive symptoms in pregnancy and a recommendation cannot be presented at this stage.

In postpartum depression, Shuganjieyu capsules compared to regular antidepressants (e.g. citalopram, paroxetine, fluoxetine, sertraline) or in combination (e.g. Chai Hu Shu Gan San and fluoxetine) seem to be promising. ^{Reference Wang, Liang and Sun74,Reference Lee, Denison, Hor and Reynolds78–Reference Zeng, Gong and Wu80} Although no significant adverse effects were reported, the safety of Chinese herbs for the newborn through breastfeeding is unknown. Given the low quality of the included studies, we weakly recommend Chinese herbs in the postpartum period. Moreover, special caution for St. John’s wort should be made as it limits the effectiveness of many prescription medicines and combining it with certain antidepressants can lead to a potentially life-threatening condition. ⁸¹

Currently, the effect of music therapy as stand-alone treatment in depressive symptoms in pregnant women is still unknown and a recommendation is not possible.

Postpartum, music therapy (e.g. light music, pure music, lullaby) combined with psychological treatment and pharmacotherapy can improve depressive symptoms, insight, pain, sleep, satisfaction and maternal bonding with no adverse side effects expected. ^{Reference Yang, Bai, Qin, Xu, Bao and Xiao82}