Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression
Abstract
Background
A meta‐analysis of 21 studies suggests the mean prevalence rate for depression across the antenatal period is 10.7%, ranging from 7.4% in the first trimester to a high of 12.8% in the second trimester. Due to maternal treatment preferences and potential concerns about fetal and infant health outcomes, diverse non‐pharmacological treatment options are needed.
Objectives
To assess the effect of interventions other than pharmacological, psychosocial, or psychological interventions compared with usual antepartum care in the treatment of antenatal depression.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2013), scanned secondary references and contacted experts in the field to identify other published or unpublished trials.
Selection criteria
All published and unpublished randomised controlled trials of acceptable quality evaluating non‐pharmacological/psychosocial/psychological interventions to treat antenatal depression.
Data collection and analysis
Both review authors participated in the evaluation of methodological quality and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for continuous data.
Main results
Six trials were included involving 402 women from the United States, Switzerland, and Taiwan. For most comparisons a single trial contributed data and there were few statistically significant differences between control and intervention groups.
In a trial with 38 women maternal massage compared with non‐specific acupuncture (control group) did not significantly decrease the number of women with clinical depression or depressive symptomatology immediately post‐treatment (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.25 to 2.53; mean difference (MD) ‐2.30, 95% CI ‐6.51 to 1.91 respectively). In another trial with 88 women there was no difference in treatment response or depression remission rates in women receiving maternal massage compared with those receiving non‐specific acupuncture (RR 1.33, 95% CI 0.82 to 2.18; RR 1.14, 95% CI 0.59 to 2.19 respectively).
In a trial with 35 women acupuncture specifically treating symptoms of depression, compared with non‐specific acupuncture, did not significantly decrease the number of women with clinical depression or depressive symptomatology immediately post‐treatment (RR 0.47, 95% CI 0.11 to 2.13; MD ‐3.00, 95% CI ‐8.10 to 2.10). However, women who received depression‐specific acupuncture were more likely to respond to treatment compared with those receiving non‐specific acupuncture (RR 1.68, 95% CI 1.06 to 2.66).
In a trial with 149 women, maternal massage by a woman's significant other, compared with standard care, significantly decreased the number of women with depressive symptomatology immediately post‐treatment (MD ‐6.70, 95% CI ‐9.77 to ‐3.63).
Further, women receiving bright light therapy had a significantly greater change in their mean depression scores over the five weeks of treatment than those receiving a dim light placebo (one trial, n = 27; MD ‐4.80, 95% CI ‐8.39 to ‐1.21). However, they were not more likely to have a treatment response or experience a higher remission rate (RR 1.79, 95% CI 0.90 to 3.56; RR 1.89, 95% CI 0.81 to 4.42).
Lastly, two trials examined the treatment effect of omega‐3 oils. Women receiving omega‐3 had a significantly lower mean depression score following eight weeks of treatment than those receiving a placebo (one trial, n = 33; MD ‐4.70, 95% CI ‐7.82 to ‐1.58). Conversely, in a smaller trial (21 women) there was no significant difference in the change in mean depression scores for women receiving omega‐3 and those receiving a placebo (MD 0.36, 95% CI ‐0.17 to 0.89), and women who received omega‐3 were no more likely to respond to treatment (RR 2.26, 95% CI 0.78 to 6.49) or have higher remission rates (RR 2.12, 95% CI 0.51 to 8.84). Women in the placebo group were just as likely to report a side effect as those in the omega‐3 group (RR 1.12, 95% CI 0.56 to 2.27).
Authors' conclusions
The evidence is inconclusive to allow us to make any recommendations for depression‐specific acupuncture, maternal massage, bright light therapy, and omega‐3 fatty acids for the treatment of antenatal depression. The included trials were too small with non‐generalisable samples, to make any recommendations.
PICOs
Plain language summary
Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression
There is not enough evidence available to determine if acupuncture, maternal massage, bright light therapy, or omega‐3 fatty acids are effective interventions in treating antenatal depression.
Approximately 12% of women will suffer from depression during their pregnancy. Research suggests that women who experience significant stress, have a history of depression, lack social support, have a history of domestic violence, are not married and living alone, and have an unintended pregnancy or poor relationships may be at a higher risk than other women of developing antenatal depression. Symptoms can include overwhelming feelings of sadness and grief, loss of interest or pleasure in activities that are usually enjoyed, feelings of worthlessness or guilt, poor sleep, a change in appetite, severe fatigue and difficulty concentrating. Unfortunately, depression during pregnancy is related to poor maternal self‐care behaviours, which may influence the baby's health; it also places a woman at significant risk of developing postpartum depression. Many women prefer not to take medication during their pregnancy and they are often interested in other complementary forms of treatment. The review found only six randomised controlled trials involving 402 women evaluating depression‐specific acupuncture (the insertion of needles into the superficial body tissues for remedial purposes), maternal massage, bright light therapy, and omega‐3 fatty acids for the treatment of antenatal depression. The included trials were too small to reach any conclusions; they also used a variety of interventions, outcome measures and comparisons. The trials provided insufficient evidence to determine if these therapies are effective treatments for antenatal depression. Further research is needed.
Authors' conclusions
Background
Description of the condition
Depression is a common complication in pregnancy, exceeding rates in the general female population. A meta‐analysis of 21 studies suggests that the mean prevalence rate of depression across the antenatal period is 10.7%, ranging from 7.4% in the first trimester to a high of 12.8% in the second trimester (Bennett 2004a). An earlier meta‐analysis including 59 studies also found that depression was common during pregnancy with a period prevalence of 18.4% across the nine months of pregnancy, with 12.7% having an episode of major depression during this time. Not surprisingly, antenatal depression is a strong risk factor of postpartum depression, and this review identified an overall prevalence of 13% within the first 12 weeks following childbirth (n = 12,810; 95% confidence interval 12.3% to 13.4%) (O'Hara 1996). Symptoms may include overwhelming feelings of sadness and grief, loss of interest or pleasure in activities usually enjoyed, feelings of worthlessness or guilt, poor sleep, a change in appetite, severe fatigue and difficulty concentrating. Numerous studies of variable methodological quality have examined antenatal depression risk factors. A systematic review that included 57 studies found the following variables were associated with a greater likelihood of antepartum depressive symptoms: anxiety in pregnancy, increased life stress, history of depression, lack of social support including intimate partner support, history of domestic violence, unintended pregnancy, single/non‐cohabitation status, and poor intimate relationship quality (Lancaster 2010). However, inconsistent findings were found related to smoking, alcohol use, illicit drug use, parity, maternal race/ethnicity, and maternal age. Five studies assessed measures of socioeconomic status and no significant associations were found. Inconsistent results were found for three sub‐components of socioeconomic status: income, employment, and education. Unfortunately, there is a general lack of awareness about antenatal depression in the community (Highet 2011), which may partially explain why it often remains under‐diagnosed (Flynn 2006). As it is an important public health issue, several professional organisations now recommend routine screening for antepartum depression to improve detection and treatment rates (ACOG 2006; NCCMH 2007).
Description of the intervention
Decisions about how to treat depression in pregnancy are complex. While untreated depression poses risk to mothers and fetuses, no treatment option comes without disadvantages. Pharmacotherapy such as anti‐depressant medication is a common treatment for moderate to severe depression that has well‐demonstrated efficacy (Lam 2009). However, information on the safety of anti‐depressant medication in pregnancy comes from observational studies which cannot rule out long‐term risks of fetal exposure. As a potential adjunct or alternative to anti‐depressant medication, psychotherapy such as cognitive‐behavioural therapy and interpersonal psychotherapy have been validated as effective treatment for general depression (Parikh 2009). A Cochrane systematic review has been completed evaluating these psychotherapies and psychosocial interventions (e.g., peer support, non‐directive counselling, nurse/midwifery home visits) for the treatment of postpartum depression (Dennis 2007a). A Cochrane systematic review of psychosocial and psychological interventions for the treatment of antenatal depression has also been completed (Dennis 2007b) where only one trial was included in the review (Spinelli 2003). However, psychotherapy may take 12 weeks or more to take effect and it may not be effective on its own in women with more severe illness (Yonkers 2009). Further, access to psychotherapy may be limited especially for those in rural and remote areas. Interventions other than pharmacological, psychosocial or psychological are also available for the treatment of depression. These "alternative" treatment options, such as light therapy and herbal supplements, are commonly used in part because of a prevalent belief that “natural is better” (Ravindran 2009). There is some reason to support the use of these therapies as a survey of primary care patients found about 11% of people with depression and anxiety reported using complementary or alternative medicine therapy (Roy‐Byrne 2005), a rate similar to the proportion of people with depression who use anti‐depressant medication (Mojtabai 2008).
There are several alternative treatment options available for depression including physical therapies (for example, bright light therapy, physical exercise, yoga, acupuncture, sleep deprivation), nutraceuticals (for example, omega‐3 fatty acids), and herbal remedies (for example, St. John's Wort) (Ravindran 2009). Light therapy is exposure to bright light where the standard “dose” is 10,000 lux (intensity) with a fluorescent light box for 30 minutes per day given in the early morning usually at home. Response typically occurs within three weeks. While the mechanism of action is still unclear, correction of disturbed circadian rhythms and modulation of serotonin and catecholamine systems are two of the theories proposed (Crowley 2012; Sohn 2005). Another treatment option is some form of physical exercise over eight to 20 weeks (average of 12 weeks), usually three times a week for 30 to 60 minutes per session. Along a similar line is yoga, which integrates physical postures, breath control, and meditation. It is practiced typically between four to eight weeks, with an average frequency of four times a week for 45 to 60 minutes per session (Ravindran 2009). Acupuncture uses special needles to pierce the skin surface at specific body points to produce particular therapeutic effects. Treatment is often four to eight weeks and the number of needles (two to 16) and sessions varies widely.
Nutraceuticals are nonprescription natural health products that are usually in concentrated forms of naturally occurring substances such as vitamins and minerals (e.g., omega‐3 fatty acids, tryptophan, S‐adenosyl‐L‐methionine (SAM‐e), folic acid, inositol, amino acids, alpha‐lactabumin, dehydroepiandrosterone (DHEA), and acetyl‐L‐carnitine) (Ravindran 2009). They are used alone or in combination to promote general well‐being. Common nutraceuticals are omega‐3 fatty acids, polyunsaturated fatty acids found in multiple biological systems. While the mechanisms of action are not fully understood, omega‐3 fatty acids have been studied in different doses and formulations, which include estyl esters of eicosapentanoic acid (EPA) or docosahexaenoic acid (DHA) or a combination of both (Freeman 2011). Herbal remedies are another sub‐category of natural health products that are derived from plants and plant extracts, such as leaves, flowers, roots, bark and berries, and sold as a non‐prescription product (Ravindran 2009). This category includes St. John's wort, Crocus sativus, Lavandula angustifolia, Rhodiola rosea, and Gingko biloba to name a few.
Why it is important to do this review
Untreated (or incompletely managed) antenatal depression has been associated with a range of adverse pregnancy complications (Bonari 2004), such as pre‐eclampsia (Kurki 2000), preterm labour (Dayan 2002), and prolonged labour (Hanlon 2009). Previous research has also demonstrated an association between mental illness and maternal smoking (Zhu 2002), abnormal endocrine and immune regulation (Clark 1996) which may impair fetal development and lead to low birthweight (Rondo 2003). There is also rapidly growing evidence that antenatal depression may impact child development (for example, Evans 2012). In addition, depression during pregnancy is one of the strongest risk factors for postpartum depression (Beck 2001), another well documented condition with significant research demonstrating a negative effect on infant and child developmental trajectories. Due to the limited amount of research evaluating the effectiveness of psychological and psychosocial interventions for the treatment of antenatal depression (Dennis 2007b) and the unknown risks of pharmacotherapy, alternative forms of treatment that have been evaluated for general depression should be examined. This review examined the effectiveness of these non‐pharmacological/psychosocial/psychological interventions in the treatment of antenatal depression, where treatment is defined as any intervention initiated among pregnant women who have been identified with depressive symptomatology (using a self‐report measure) or diagnosed with depression (using a clinical interview).
Objectives
The primary objective of this review was to assess the effects, on mothers, infants and their families, of interventions other than pharmacological, psychosocial, or psychological interventions compared with usual antepartum care in the treatment of antenatal depression.
Methods
Criteria for considering studies for this review
Types of studies
All published and unpublished randomised controlled trials examining interventions other than pharmacological, psychosocial, or psychological interventions in which the primary or secondary aim was to treat antenatal depression. Quasi‐randomised trials (e.g., those randomised by delivery date, or odd versus even medical record numbers) were excluded from the analysis.
Types of participants
Pregnant women identified with antenatal depression (variously defined).
Types of interventions
Any form of standard or usual care compared to a variety of interventions (including bright light therapy, physical exercise, yoga, acupuncture, sleep deprivation), nutraceuticals (for example, omega‐3 fatty acids), and herbal remedies (for example, St. John's Wort) delivered via telephone, home or clinic visits, or individual or group sessions antenatally by a professional (e.g., nurse, midwife, childbirth educator, physician, psychiatrist, psychologist) or lay person (e.g., a specially trained woman from the community, student, research assistant).
Types of outcome measures
Primary outcomes
Maternal
1. Antenatal depression (as variously defined and measured by trialists).
Secondary outcomes
Maternal
2. Postpartum depression (as variously defined and measured by trialists).
3. Maternal mortality and serious morbidity including self‐harm and suicide attempts.
4. Maternal‐infant attachment.
5. Anxiety.
6. Maternal stress.
7. Maternal perceived social support.
8. Maternal dissatisfaction with care provided.
Infant
9. Breastfeeding duration (variously defined).
10. Breastfeeding level (exclusive, almost exclusive, high, partial, token, bottle‐feeding).
11. Infant health parameters including immunisation, accidental injury, non‐accidental injury.
12. Infant developmental assessments (variously defined).
13. Child abuse and/or neglect.
Family outcomes
12. Marital/partner discord.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Co‐ordinator (31 January 2013).
The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from:
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monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
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weekly searches of MEDLINE;
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weekly searches of Embase;
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handsearches of 30 journals and the proceedings of major conferences;
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weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL, MEDLINE and Embase, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group.
Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co‐ordinator searches the register for each review using the topic list rather than keywords.
Searching other resources
We examined secondary references and contacted experts in the field. We did not apply any language restrictions.
Data collection and analysis
For the methods used when assessing the trials identified in the previous version of this review, seeAppendix 1. For this update we used the following methods when assessing the reports identified by the updated search.
Selection of studies
Both review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We resolved any uncertainties regarding the appropriateness for inclusion through discussion or consultation with a third person.
Data extraction and management
We designed a form to extract data. For eligible studies, both review authors independently extracted data using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person. We entered data into Review Manager software (RevMan 2012) and checked for accuracy. When information regarding any of the above was unclear, we attempted to contact the authors of the original reports to provide further details.
Assessment of risk of bias in included studies
The review authors independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreement by discussion or by involving a third assessor.
(1) Sequence generation (checking for possible selection bias)
We have described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.
We assessed the method as:
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low risk of bias (any truly random process, e.g. random number table; computer random number generator);
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high risk of bias (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number);
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unclear.
(2) Allocation concealment (checking for possible selection bias)
We have described for each included study the method used to conceal the allocation sequence and have determined whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.
We assessed the methods as:
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low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
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high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth);
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unclear.
(3) Blinding (checking for possible performance bias)
We have described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding could not have affected the results. We assessed blinding separately for different outcomes or classes of outcomes.
We assessed the methods as:
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low, high or unclear risk of bias for participants;
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low, high or unclear risk of bias for personnel;
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low, high or unclear risk of bias for outcome assessors.
(4) Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations)
We have described for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We have stated whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported, or supplied by the trial authors, we have re‐included missing data in the analyses which we undertake. We assessed methods as:
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low risk of bias;
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high risk of bias;
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unclear.
(5) Selective reporting bias
We have described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.
We assessed the methods as:
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low risk of bias (where it is clear that all of the study’s pre‐specified outcomes and all expected outcomes of interest to the review have been reported);
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high risk of bias (where not all the study’s pre‐specified outcomes have been reported; one or more reported primary outcomes were not pre‐specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported);
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unclear.
(6) Other sources of bias
We have described for each included study any important concerns we have about other possible sources of bias such as baseline imbalance between groups.
We assessed whether each study was free of other problems that could put it at risk of bias:
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low risk of other bias;
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high risk of other bias;
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unclear risk of other bias.
(7) Overall risk of bias
We made explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Cochrane Handbook (Higgins 2011). With reference to (1) to (6) above, we assessed the likely magnitude and direction of the bias and whether we consider it is likely to impact on the findings. We planned to explore the impact of the level of bias through undertaking sensitivity analyses ‐ seeSensitivity analysis.
Measures of treatment effect
Dichotomous data
For dichotomous data, we have presented results as summary risk ratio with 95% confidence intervals.
Continuous data
For continuous data, we used the mean difference if outcomes were measured in the same way between trials. We planned to use the standardised mean difference to combine trials that measured the same outcome, but used different methods.
Unit of analysis issues
Cluster‐randomised trials
We planned to include cluster‐randomised trials in the analyses along with individually‐randomised trials. In this version of the review we did not identify any cluster‐randomised trials, however, if such trials are included in future updates, we will adjust their sample sizes using the methods described in the Cochrane Handbook (Higgins 2011) using an estimate of the intracluster correlation co‐efficient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. If we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identify both cluster‐randomised trials and individually‐randomised trials, we plan to synthesise the relevant information. We will consider it reasonable to combine the results from both if there is little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely.
We will also acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit.
Cross‐over trials
We did not include cross‐over trials.
Other unit of analysis issues
For trials with more than two treatment groups, where possible we combined arms and carried out pair‐wise comparisons.
Dealing with missing data
For included studies, we noted levels of attrition. We explored the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.
For all outcomes, we carried out analyses, as far as possible, on an intention‐to‐treat basis, i.e. we attempted to include all participants randomised to each group in the analyses, and all participants were analysed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial was the number randomised minus any participants whose outcomes were known to be missing.
Assessment of heterogeneity
We assessed statistical heterogeneity in each meta‐analysis using the T2, I² and Chi² statistics. We have regarded heterogeneity as substantial if the T2 was greater than zero and either the I2 was greater than 30% or there was a low P value (less than 0.10) in the Chi² test for heterogeneity.
Assessment of reporting biases
Had there been 10 or more studies in the meta‐analysis, we would have investigated reporting biases (such as publication bias) using funnel plots. We would have assessed funnel plot asymmetry visually. If asymmetry was suggested by a visual assessment, we would have performed exploratory analyses to investigate it.
Data synthesis
We carried out statistical analysis using the Review Manager software (RevMan 2012). We used fixed‐effect meta‐analysis for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect: i.e. where trials examined the same intervention, and the trials’ populations and methods were judged sufficiently similar. If there was clinical heterogeneity sufficient to expect that the underlying treatment effects would differ between trials, or if substantial statistical heterogeneity was detected, we planned to use random‐effects meta‐analysis to produce an overall summary, if an average treatment effect across trials was considered clinically meaningful. The random‐effects summary would have been treated as the average range of possible treatment effects and we would have discussed the clinical implications of treatment effects differing between trials. If the average treatment effect was not considered to be clinically meaningful, we would not combine trials.
If we had used random‐effects analyses, the results would have been presented as the average treatment effect with its 95% confidence interval, and the estimates of T2 and I2.
Subgroup analysis and investigation of heterogeneity
Due to the limited number of included studies, we were unable to perform any subgroup analyses.
Sensitivity analysis
We planned to perform sensitivity analyses for the primary outcome in instances in which any of the following occurred:
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a high risk of bias associated with the methodological quality of included trials;
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incomplete outcome data (more that 20% missing data) for any of the included trials.
Results
Description of studies
See Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.
Results of the search
Overall, there were 18 studies of non‐pharmacological/psychosocial/psychological interventions identified from the literature search. Of the these studies, only six were suitable for inclusion in this review (Field 2009a; Freeman 2008; Manber 2004; Manber 2010; Su 2008; Wirz‐Justice 2011).
Included studies
Six randomised controlled trials, reported between 2004 and 2011, were identified and met the inclusion criteria (Field 2009a; Freeman 2008; Manber 2004; Manber 2010; Su 2008; Wirz‐Justice 2011). In total, 402 women were included in the meta‐analysis. Of the six trials, four were conducted in the United States (Field 2009a; Freeman 2008; Manber 2004; Manber 2010) while the other two trials were conducted in Switerland (Wirz‐Justice 2011) and Taiwan (Su 2008). All trials included the outcome of depression in pregnancy; one trial included an anxiety measure (Field 2009a). Due to the limited number of included studies we were unable to perform any subgroup or sensitive analyses.
Definition of depression
A diagnosis of depression is made by a clinician following examination and clinical assessment; most of the studies included in the review did not report the number of women diagnosed with depression, but instead reported scores on various scales measuring symptoms of depression such as low mood or suicidal ideation (depressive symptomatology). In all trials, depressive symptomatology was assessed using a self‐report measure; only one trial included a diagnosis of depression following clinical interview as an outcome (Manber 2004). The most common self‐report measure used was the Hamilton Rating Scale for Depression (HRSD) (Freeman 2008; Manber 2004; Manber 2010; Su 2008; Wirz‐Justice 2011). Two trials used the Beck Depression Inventory (BDI) (Manber 2004; Su 2008) and two trials used the Edinburgh Postnatal Depression Scale (EPDS) (Freeman 2008; Su 2008). One trial incorporated the Center for Epidemiologic Studies Depression Scale (CES‐D) (Field 2009a) and one trial used the Structural Interview Guide for the Hamilton Depression and Anxiety Scales (SIGH‐AD) (Wirz‐Justice 2011). Several trials examined a difference in mean scores (Field 2009a; Manber 2004; Su 2008), while others examined a change in mean scores (Freeman 2008; Wirz‐Justice 2011). Three trials examined both treatment response (defined in trials as a 50% reduction in baseline depressive symptomatology scores) and depression remission (defined in trials as a depressive symptomatology score below a specific cut‐off indicating no symptoms of depression) (Manber 2010; Su 2008; Wirz‐Justice 2011). Due to the significant differences in the timing of outcome data, we included the outcome assessment point "immediately post‐treatment antenatally". While two trials examined depressive symptomatology scores both antenatally and postnatally (Field 2009a; Manber 2004), one trial did not provide usable postnatal data that could be included in the review (Field 2009a).
Types of interventions
Interventions evaluated in this review included the physical therapies of acupuncture (Manber 2004; Manber 2010), maternal massage (Field 2009a), bright light therapy (Wirz‐Justice 2011), and the nutraceutical therapy of omega‐3 fatty acids (Freeman 2008; Su 2008). No studies were found that examined other physical therapies such as exercise, yoga, or sleep deprivation and other nutraceutical therapies such as DHEA. No herbal remedies such as St John's Wort were included in this review.
Excluded studies
The nine studies that were excluded examined the following interventions: acupuncture (Bosco 2007), omega‐3 fatty acids (Doornbos 2009; Mozurkewich 2011), bright light therapy (Epperson 2004), maternal massage (Field 2004; Field 2009b), relaxation and guided imagery (Gedde‐Dahl 2012), education (Hayes 2001), and early/late sleep therapy (Parry 2010). Three trials (Bosco 2007; Field 2004; Field 2009b) lacked the methodologic quality required for inclusion while three other trials (Doornbos 2009; Hayes 2001; Mozurkewich 2011) specifically focused on the prevention of postpartum depression rather than the treatment of antenatal depression. The trial by Mozurkewich 2011 is currently ongoing and the decision to exclude was based on a published trial protocol.
There are three studies meeting inclusion criteria that are awaiting classification (Field 2008; Field 2012; Rees 2008); authors have been contacted to obtain the data needed for inclusion.
Risk of bias in included studies
The methodological quality of the included trials was not strong. The sample sizes were well below 100 except for two trials (Field 2009a; Manber 2010).
Summaries of 'Risk of bias' assessments are presented in Figure 1 and Figure 2.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Although randomisation was conducted, there were no details provided regarding allocation generation or concealment in four trials (Field 2009a; Freeman 2008; Manber 2004; Su 2008). The other two trials used block randomisation generated by computer (Manber 2010; Wirz‐Justice 2011).
Blinding
In only two trials (Manber 2010; Wirz‐Justice 2011) was it clear that the outcome assessors were blinded to group allocation.
Incomplete outcome data
Loss of participants to follow‐up was very high (at least 30%) in three trials (Field 2009a; Su 2008; Wirz‐Justice 2011).
Selective reporting
It was unclear from assessment of the published study reports whether or not selective reporting had occurred. Trial protocols were not assessed. Additional information from one trial author has been requested (Field 2009a).
Other potential sources of bias
All trials but two (Field 2009a; Manber 2004) systematically examined side effects.
Effects of interventions
We have set out results for each type of intervention separately. While all trials reported depression or depressive symptomatology following treatment no trials reported on infant or family outcomes. While postpartum depression was one of our secondary outcomes, to avoid repetition in both the analyses and text, we have reported results for postpartum depression together with results for the antenatal period. For our primary outcomes, outcome measures for each individual treatment approach varied resulting in no data being combined in meta‐analysis.
Comparison one: maternal massage versus non‐specific acupuncture (control group)
A. Maternal primary outcomes
Outcome: Clinical depression
Maternal massage compared to non‐specific acupuncture (control group) did not significantly decrease the number of women diagnosed with clinical depression (DSM‐IV criteria) immediately post‐treatment (one trial, n = 38; risk ratio (RR) 0.80, 95% confidence interval (CI) 0.25 to 2.53) or at final assessment at 10 weeks postpartum (one trial, n = 32; RR 1.93, 95% CI 0.37 to 10.01) Analysis 1.1.
Outcome: Depressive symptomatology
Maternal massage, compared to non‐specific acupuncture did not significantly decrease the number of women with depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD) immediately post‐treatment (one trial, n = 38; mean difference (MD) ‐2.30, 95% CI ‐6.51 to 1.91) or at final assessment at 10 weeks postpartum (one trial, n = 33; MD ‐0.20, 95% CI ‐4.91 to 4.51) Analysis 1.2. Similarly, there was no beneficial effect found when depressive symptomatology was measured using the Beck Depression Inventory (BDI_ immediately post‐treatment (one trial, n = 38; MD ‐2.20, 95% CI ‐5.22 to 0.82) or at final assessment at 10 weeks postpartum (one trial, n = 33; MD ‐0.60, 95% CI ‐6.23 to 5.03) Analysis 1.3.
Outcome: Treatment response
Treatment response rates (a 50% reduction in HRSD scores from baseline) did not differ between women receiving maternal massage and those receiving non‐specific acupuncture (one trial, n = 88; RR 1.33, 95% CI 0.82 to 2.18) Analysis 1.4.
Outcome: Depression remission
Remission rates (HRSD score less than eight) were not significantly different between the women receiving prenatal massage and those receiving non‐specific acupuncture (one trial, n = 88; RR 1.14, 95% CI 0.59 to 2.19) Analysis 1.5.
Comparison two: depression‐specific acupuncture versus non‐specific acupuncture (control group)
A. Maternal primary outcomes
Outcome: Clinical depression
Acupuncture specifically treating symptoms of depression, compared to non‐specific acupuncture did not significantly decrease the number of women diagnosed with clinical depression (DSM‐IV criteria) immediately post‐treatment (one trial, n = 35; RR 0.47, 95% CI 0.11 to 2.13) or at final assessment at 10 weeks postpartum (one trial, n = 32; RR 0.64, 95% CI 0.06 to 6.39) Analysis 2.1.
Outcome: Depressive symptomatology
Acupuncture specifically treating symptoms of depression, compared to non‐specific acupuncture did not significantly decrease the number of women with depressive symptomatology as measured by the HRSD immediately post‐treatment (one trial, n = 35; MD ‐3.00, 95% CI ‐8.10 to 2.10) or at final assessment at 10 weeks postpartum (one trial, n = 32; MD ‐0.90, 95% CI ‐5.72 to 3.92) Analysis 2.2. Similarly, there was no beneficial effect found when depressive symptomatology was measured using the BDI immediately post‐treatment (one trial, n = 35; MD ‐3.00, 95% CI ‐6.85 to 0.85) or at final assessment at 10 weeks postpartum (one trial, n = 32; MD ‐3.90, 95% CI ‐9.96 to 2.16) Analysis 2.3.
Outcome: Treatment response
Women who received depression‐specific acupuncture were more likely to have a treatment response rates (a 50% reduction in HRSD scores from baseline) than those receiving non‐specific acupuncture (one trial, n = 86; RR 1.68, 95% CI 1.06 to 2.66) Analysis 2.4.
Outcome: Depression remission
Remission rates (HRSD score less than eight) were not significantly different between the women receiving depression‐specific acupuncture and those receiving non‐specific acupuncture (one trial, n = 86; RR 1.26, 95% CI 0.67 to 2.40) Analysis 2.5.
Comparison three: maternal massage versus standard care
A. Maternal primary outcomes
Outcome: Depressive symptomatology
Massage by a significant other, compared to standard care significantly decreased the number of women with depressive symptomatology as measured by the Center for Epidemiological Studies‐Depression Scale (CES‐D) immediately post‐treatment (one trial, n = 149; MD ‐6.70, 95% CI ‐9.77 to ‐3.63) Analysis 3.1.
B. Maternal secondary outcomes
Outcome: Anxiety
Massage by a significant other, compared to standard care did not significantly decreased the number of women with anxiety as measured by the State Anxiety Inventory (STAI) immediately post‐treatment (one trial, n = 149; MD ‐1.80, 95% CI ‐5.04 to 1.44) Analysis 3.2.
Comparison four: bright light therapy versus placebo
A. Maternal primary outcomes
Outcome: Depressive symptomatology
Women receiving bright light therapy had a significantly greater change in their mean HRSD scores over the five weeks of treatment than those receiving a dim light placebo (one trial, n = 27; MD ‐4.80, 95% CI ‐8.39 to ‐1.21 ) Analysis 4.1. A similar significant change favouring the bright light therapy group was found using the Structural Interview Guide for the Hamilton Depression and Anxiety Scale (SIGH‐AD) (one trial, n = 27; MD ‐5.00, 95% CI ‐10.00 to 0.00) Analysis 4.2.
Outcome: Treatment response
Women who received bright light therapy were no more likely to have a treatment response (a 50% reduction in HRSD scores from baseline) than those receiving a dim light placebo (one trial, n = 27; RR 1.79, 95% CI 0.90 to 3.56) Analysis 4.3. A similar non‐significant treatment response was found with the SIGH‐AD (one trial, n = 27; RR 2.06, 95% CI 0.90 to 4.74) Analysis 4.4.
Outcome: Depression remission
Remission rates (HRSD score less than eight) were not significantly different between the women receiving bright light therapy and those receiving a dim light placebo (one trial, n = 27; RR 1.89, 95% CI 0.81 to 4.42) Analysis 4.5. A similar non‐significant remission rate was found with the SIGH‐AD (score less than eight)(one trial, n = 27; RR 1.72, 95% CI 0.40 to 7.32) Analysis 4.6.
Comparison five: omega‐3 fatty acids versus placebo
A. Maternal primary outcomes
Outcome: Depressive symptomatology
Two trials examined the treatment effect of omega‐3 fatty acids. Women receiving omega‐3 fatty acids had a significantly lower mean HRSD score following eight weeks of treatment than those receiving a placebo (one trial, n = 33; MD ‐4.70, 95% CI ‐7.82 to ‐1.58) Analysis 5.1. A similar significant difference in mean scores favouring the omega‐3 group at eight weeks following treatment was found using the Edinburgh Postnatal Depression Scale (EPDS) (one trial, n = 33; MD ‐5.80, 95% CI ‐9.85 to ‐1.75) Analysis 5.2 and BDI (one trial, n = 33; MD ‐9.00, 95% CI ‐15.76 to ‐2.24) Analysis 5.3. Conversely, in a smaller trial there was no significant difference in the change in mean HRSD scores from baseline to eight weeks of treatment for women receiving omega‐3 fatty acids and those receiving a placebo (one trial, n = 21; MD 0.36, 95% CI ‐0.17 to 0.89) Analysis 5.4. Similary, there was no significant difference in the change in mean EPDS scores from baseline to eight weeks of treatment between the two group (one trial, n = 21; MD ‐0.03, 95% CI ‐0.75 to 0.69) Analysis 5.5.
Outcome: Treatment response
Women who received omega‐3 fatty acids were no more likely to have a treatment response (a 50% reduction in HRSD scores from baseline) than those receiving a placebo (one trial, n = 24; RR 2.26, 95% CI 0.78 to 6.49) Analysis 5.6.
Outcome: Depression remission
Remission rates (HRSD score less than eight) were not significantly different between the women receiving omega‐3 fatty acids and those receiving a placebo (one trial, n = 24; RR 2.12, 95% CI 0.51 to 8.84) Analysis 5.7.
B. Non‐prespecified outcomes
Outcome: Side effects
Women in the placebo group were just as likely to report a side effect as those in the omega‐3 fatty acids group (two trials, n = 57; RR 1.12, 95% CI 0.56 to 2.27) Analysis 5.8.
Discussion
Summary of main results
Six trials were included in this review incorporating 402 women from the United States, Switzerland, and Taiwan. The body of evidence provided in this review does not allow for a strong conclusion regarding non‐pharmacological/psychosocial/psychological interventions for the treatment of antenatal depression. Only six trials were included and all treatment approaches had two or less trials providing evidence for effectiveness (acupuncture = two trials; massage = one trial; bright light therapy = one trial; omega‐3 fatty acids = two trials). Outcome measures for each individual treatment approach varied resulting in no data being combined for the primary outcome. The methodological quality for most of the included trials was not strong with many common limitations such as unclear randomisation procedures, small and homogeneous samples, unclear blinding of outcome assessors, and high attrition rates. These limitations render any results questionable.
One three‐armed trial tested the efficacy of maternal massage and depression‐specific acupuncture for the treatment of depressed pregnant women (Manber 2004). This pilot study of 61 US women found that neither the 12 20‐minute massage sessions nor the 12 25‐ to 30‐minute depression specific‐acupuncture sessions were more effective in reducing depressive symptoms than non‐specific acupuncture. In a larger trial by the same group (Manber 2010), maternal massage sessions again were not more effective in achieving a significant treatment response or obtaining depression remission than non‐specific acupuncture. However, this trial did find that depression‐specific acupuncture was more likely to produce a treatment response than non‐specific acupuncture; no effect was found related to depression remission. One trial evaluated the effect of maternal massage by a women's significant other versus standard care (Field 2009a). Women who received the massage where significantly more likely to experience a decrease in depressive symptomatology than those who received standard care; there was no impact on maternal anxiety. In a trial by Wirz‐Justice 2011, bright light therapy was not more effective than inactive bright light therapy in providing a treatment response or promoting depression remission. However, there was a significantly greater change in mean depression scores in those who received the active bright light therapy than those who received inactive therapy. While two trials evaluated omega‐3 fatty acids for the treatment of antenatal depression, neither trial evaluated a similar outcome so their results could not be combined. In the trial by Su 2008, women who received omega‐3 fatty acids were not more likely to achieve depression remission or have a treatment response. However, in this trial women who received omega‐3 fatty acids had significantly lower mean depressive symptoms scores following treatment than those receiving a placebo. In the trial by Freeman 2008, there was no significant difference in the change in mean depression scores for women receiving omega‐3 fatty acids and those receiving a placebo. In both trials, very few women reported a side effect and there was no differences in reporting an event between those who received omega‐3 fatty acids and those who received a placebo.
Overall completeness and applicability of evidence
The treatment of antenatal depression using non‐psychosocial/psychological interventions is an area that has been neglected, despite antenatal depression being a significant public health concern. This updated review added five new trials to the original review which only included one study (Manber 2004). The original trial in this review tested the efficacy of massage and depression‐specific acupuncture for the treatment of depressed pregnant women. Another larger, acupuncture trial (n = 149) has been added by the same research group (Manber 2010). This trial found acupuncture specific for depression was associated with a significantly higher rate of response compared to control acupuncture (acupuncture not specific for depression). Several sample characteristics limit the generalisability of the results including the high education and socioeconomic status, predominance of Caucasians, and exclusion of comorbid mental and medical disorders. As such, the results are not generalisable to specific minority groups or pregnant women with other mental health concerns. While this trial alone does not provide strong evidence to indicate acupuncture should be used for the treatment of antenatal depression, the results are consistent with two other recent reviews that found acupuncture, including manual‐, electrical‐, and laser‐based, is a generally beneficial, well‐tolerated, and safe treatment for depression (Wang 2008; Wu 2012). The studies included in these reviews had many methodological limitations such as small sample size and unclear description of enrolment criteria, randomisation or blinding, and forms of acupuncture used. Recently, a randomised, subject‐ and assessor‐blind, parallel‐group, sham‐controlled trial was conducted to evaluate the effect of acupuncture on postpartum depression among 20 Hong Kong mothers (Chung 2012). Although this trial was generally well designed, no significant differences were found between the two groups. This negative finding may possibly be the result of a type II error as the study may have had insufficient power to detect differences between the study groups due to the small sample size. Despite consistent methodological limitations, there is growing evidence to suggest that acupuncture may be beneficial for the treatment of depression and large, well‐designed randomised controlled trials are warranted to evaluate the effectiveness of acupuncture with depressed pregnant women.
Very few studies have been conducted to evaluate the effect of massage on the treatment of antenatal depression. The one trial included in this review that evaluated maternal massage compared with standard treatment care (Field 2009a) found women who received the massage intervention were significantly more like to experience a decreased depressive symptomatology. However, in this trial the massage intervention was provided by the woman's significant other. Given that a lack of support and a poor intimate partner relationship are significant risk factors for antenatal depression (Lancaster 2010), the beneficial effect found in the trial may have been due to the additional attention provided by the women's significant other rather than the intervention itself. The other trial in this review that examined massage by a therapist versus non‐specific acupuncture (control group) found no beneficial effect of massage (Manber 2004). In a recent systematic review of 17 randomised controlled trials of moderate quality, massage therapy was found to be effective in alleviating depressive symptoms (Hou 2010). Additional research in this area is warranted; however, standardisation of massage therapy protocols are required to provide comparable results.
In this review, only one trial was included that evaluated the effect of bright light therapy (Wirz‐Justice 2011). While no beneficial effect on treatment response or depression remission was found, there was a significantly greater change in mean depression scores from baseline in those who received the active bright light therapy than those who received inactive therapy. This result is consistent with a systematic review of light therapy for non‐seasonal depression that reported the efficacy of bright light against placebo conditions (Even 2008). This review noted that most of the studies included had small numbers, inadequate control conditions, and were short‐term (two to five weeks). The side effects of bright light therapy include headache, eye strain, nausea, and agitation, but these are generally mild and rarely lead to treatment discontinuation (Ravindran 2009). Bright light therapy may be an attractive treatment for antenatal depression because it is low cost, home‐based, and has a much lower side effect profile than pharmacotherapy. In a interesting review by Crowley 2012, there are several factors related to the pathophysiology of depression and response to light which might make bright light especially suitable for antenatal depression. For example, bright light treatment could potentially offset insufficient low levels of light exposure; pathological hormonal profiles; co‐morbidities, including disturbed sleep and fatigue; and serotonergic dysregulation which has been linked to inadequate maternal behaviour. Only three studies (Epperson 2004; Oren 2002; Wirz‐Justice 2011) have examined bright light therapy in depressed pregnant women. Larger randomised controlled trials are needed since bright light may be preferable to other types of treatment.These trials should have adequate control conditions, provide treatment for five weeks or longer, provide comparative effectiveness, and address co‐morbidities that bright light could alleviate such as anxiety, disturbed sleep, and fatigue.
While omega‐3 fatty acids are one of the most widely used non‐vitamin supplements, there are insufficient data from adequately powered controlled trials to say whether omega‐3 fatty acids are efficacious in the treatment of depression (Freeman 2011). Most randomised controlled trials have been small and of short duration and have yielded inconsistent findings (Freeman 2011). Further, the majority of trials have evaluated omega‐3 fatty acids as an adjunctive treatment and the doses and composition of the omega‐3 supplements have been extremely variable. In this review, two trials (Freeman 2008; Su 2008) evaluated the effect of omega‐3 fatty acids as a treatment for antenatal depression. One trial (Su 2008) found a positive effect of omega‐3 fatty acids on depressive symptomatology immediately post‐treatment while the trial (Freeman 2008) did not. However, there was significant improvement from baseline in both groups in this trial, which could be attributed to the supportive therapy that all women in both groups received. It is important to note that this trial was very small (n = 21) and insufficiently powered to detect differences between study groups. Given the growing evidence that supports the role that omega‐3 fatty acids plays in mental illness and health (Freeman 2011), research examining the effect of omega‐3 supplementation in the treatment of antenatal depression is warranted. Future trials should determine if: (1) omega‐3 fatty acids are efficacious as a monotherapy; (2) there is an optimal dose, ratio of EPA/DHA, and treatment course; and (3) the dose needs to be tailored to individuals based on dietary habits (Freeman 2011).
There were no trials evaluating other non‐psychosocial/psychological interventions in the treatment of antenatal depression such as physical exercise. Exercise is a relatively low‐cost intervention, with minimal side effects, and there is now evidence to support the antidepressant effects of exercise in general and clinical populations (Lawlor 2001). Limited evidence also supports a relationship between participation in exercise and a reduction in postpartum depression. For example, a review article explored the potential role of exercise, particularly pram walking, as an adjunctive treatment for postpartum depression (Daley 2007). Two small randomised controlled trials conducted in Australia were included in this review, which supported exercise as a useful treatment for women with postpartum depression (Armstrong 2003; Armstrong 2004). Given the reluctance by some women to use anti‐depressant medication antenatally and the limited availability of psychosocial and psychological therapies (Dennis 2007b), exercise as a therapeutic possibility for depressed pregnant women deserves further exploration.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Maternal massage versus non‐specific acupuncture (control group), Outcome 1 Diagnosis of depression.
Comparison 1 Maternal massage versus non‐specific acupuncture (control group), Outcome 2 Depressive symptomatology ‐ HRSD.
Comparison 1 Maternal massage versus non‐specific acupuncture (control group), Outcome 3 Depressive symptomatology ‐ BDI.
Comparison 1 Maternal massage versus non‐specific acupuncture (control group), Outcome 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline).
Comparison 1 Maternal massage versus non‐specific acupuncture (control group), Outcome 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8.
Comparison 2 Depression‐specific acupuncture versus non‐specific acupuncture (control group), Outcome 1 Diagnosis of depression.
Comparison 2 Depression‐specific acupuncture versus non‐specific acupuncture (control group), Outcome 2 Depressive symptomatology ‐ HRSD.
Comparison 2 Depression‐specific acupuncture versus non‐specific acupuncture (control group), Outcome 3 Depressive symptomatology ‐ BDI.
Comparison 2 Depression‐specific acupuncture versus non‐specific acupuncture (control group), Outcome 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline).
Comparison 2 Depression‐specific acupuncture versus non‐specific acupuncture (control group), Outcome 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8.
Comparison 3 Maternal massage versus standard care (control group), Outcome 1 Depressive symptomatology ‐ CES‐D.
Comparison 3 Maternal massage versus standard care (control group), Outcome 2 Anxiety ‐ STAI.
Comparison 4 Bright light therapy versus placebo, Outcome 1 Depressive symptomatology ‐ HRSD mean change score post‐treatment.
Comparison 4 Bright light therapy versus placebo, Outcome 2 Depressive symptomatology ‐ SIGH‐AD mean change score post‐treatment.
Comparison 4 Bright light therapy versus placebo, Outcome 3 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline).
Comparison 4 Bright light therapy versus placebo, Outcome 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ SIGH‐AD reduction of 50% from baseline).
Comparison 4 Bright light therapy versus placebo, Outcome 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8.
Comparison 4 Bright light therapy versus placebo, Outcome 6 Depression remission post‐treatment antenatally (depressive symptomatology ‐ SIGH‐AD score less than 8 following treatment.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 1 Depressive symptomatology ‐ HRSD.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 2 Depressive symptomatology ‐ EPDS.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 3 Depressive symptomatology ‐ BDI.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 4 Depressive symptomatology ‐ HRSD mean change score post‐treatment.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 5 Depressive symptomatology ‐ EPDS mean change score post‐treatment.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 6 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline).
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 7 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8.
Comparison 5 Omega‐3 fatty acids versus placebo, Outcome 8 Side effects reported (including nausea and dizziness).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Diagnosis of depression Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Immediately post‐treatment antenatally | 1 | 38 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.8 [0.25, 2.53] |
| 1.2 Final assessment postnatally | 1 | 32 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.93 [0.37, 10.01] |
| 2 Depressive symptomatology ‐ HRSD Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.1 Immediately post‐treatment antenatally | 1 | 38 | Mean Difference (IV, Fixed, 95% CI) | ‐2.30 [‐6.51, 1.91] |
| 2.2 Final assessment postnatally | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐4.91, 4.51] |
| 3 Depressive symptomatology ‐ BDI Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 3.1 Immediately post‐treatment antenatally | 1 | 38 | Mean Difference (IV, Fixed, 95% CI) | ‐2.20 [‐5.22, 0.82] |
| 3.2 Final assessment postnatally | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐0.60 [‐6.23, 5.03] |
| 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline) Show forest plot | 1 | 88 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.33 [0.82, 2.18] |
| 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8 Show forest plot | 1 | 88 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.59, 2.19] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Diagnosis of depression Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Immediately post‐treatment antenatally | 1 | 35 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.48 [0.11, 2.13] |
| 1.2 Final assessment postnatally | 1 | 32 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.06, 6.39] |
| 2 Depressive symptomatology ‐ HRSD Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.1 Immediately post‐treatment antenatally | 1 | 35 | Mean Difference (IV, Fixed, 95% CI) | ‐3.0 [‐8.10, 2.10] |
| 2.2 Final assessment postnatally | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐0.90 [‐5.72, 3.92] |
| 3 Depressive symptomatology ‐ BDI Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 3.1 Immediately post‐treatment antenatally | 1 | 35 | Mean Difference (IV, Fixed, 95% CI) | ‐3.0 [‐6.85, 0.85] |
| 3.2 Final assessment postnatally | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐3.90 [‐9.96, 2.16] |
| 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline) Show forest plot | 1 | 86 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.68 [1.06, 2.66] |
| 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8 Show forest plot | 1 | 86 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.26 [0.67, 2.40] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Depressive symptomatology ‐ CES‐D Show forest plot | 1 | 149 | Mean Difference (IV, Fixed, 95% CI) | ‐6.70 [‐9.77, ‐3.63] |
| 1.1 Immediately post‐treatment antenatally | 1 | 149 | Mean Difference (IV, Fixed, 95% CI) | ‐6.70 [‐9.77, ‐3.63] |
| 2 Anxiety ‐ STAI Show forest plot | 1 | 149 | Mean Difference (IV, Fixed, 95% CI) | ‐1.80 [‐5.04, 1.44] |
| 2.1 Immediately post‐treatment antenatally | 1 | 149 | Mean Difference (IV, Fixed, 95% CI) | ‐1.80 [‐5.04, 1.44] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Depressive symptomatology ‐ HRSD mean change score post‐treatment Show forest plot | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | ‐4.8 [‐8.39, ‐1.21] |
| 2 Depressive symptomatology ‐ SIGH‐AD mean change score post‐treatment Show forest plot | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | ‐5.00 [‐10.00, 0.00] |
| 3 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline) Show forest plot | 1 | 27 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.79 [0.90, 3.56] |
| 4 Treatment response post‐treatment antenatally (depressive symptomatology ‐ SIGH‐AD reduction of 50% from baseline) Show forest plot | 1 | 27 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.06 [0.90, 4.74] |
| 5 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8 Show forest plot | 1 | 27 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.89 [0.81, 4.42] |
| 6 Depression remission post‐treatment antenatally (depressive symptomatology ‐ SIGH‐AD score less than 8 following treatment Show forest plot | 1 | 27 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.72 [0.40, 7.32] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Depressive symptomatology ‐ HRSD Show forest plot | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐4.70 [‐7.82, ‐1.58] |
| 1.1 Immediately post‐treatment antenatally | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐4.70 [‐7.82, ‐1.58] |
| 2 Depressive symptomatology ‐ EPDS Show forest plot | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐5.80 [‐9.85, ‐1.75] |
| 2.1 Immediately post‐treatment antenatally | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐5.80 [‐9.85, ‐1.75] |
| 3 Depressive symptomatology ‐ BDI Show forest plot | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐9.0 [‐15.76, ‐2.24] |
| 3.1 Immediately post‐treatment antenatally | 1 | 33 | Mean Difference (IV, Fixed, 95% CI) | ‐9.0 [‐15.76, ‐2.24] |
| 4 Depressive symptomatology ‐ HRSD mean change score post‐treatment Show forest plot | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | 0.36 [‐0.17, 0.89] |
| 5 Depressive symptomatology ‐ EPDS mean change score post‐treatment Show forest plot | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | ‐0.03 [‐0.75, 0.69] |
| 6 Treatment response post‐treatment antenatally (depressive symptomatology ‐ HRSD reduction of 50% from baseline) Show forest plot | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.26 [0.78, 6.49] |
| 7 Depression remission post‐treatment antenatally (depressive symptomatology ‐ HRSD score less than 8 Show forest plot | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.12 [0.51, 8.84] |
| 8 Side effects reported (including nausea and dizziness) Show forest plot | 2 | 57 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.12 [0.56, 2.27] |
