YPMED-04137; No of Pages 11 Preventive Medicine xxx (2014) xxx–xxx

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Preventive Medicine journal homepage: www.elsevier.com/locate/ypmed

Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses☆ Juan Ángel Bellón a,⁎,1, Patricia Moreno-Peral b, Emma Motrico c, Alberto Rodríguez-Morejón d, Ana Fernández e,f, Antoni Serrano-Blanco g, Edurne Zabaleta-del-Olmo h, Sonia Conejo-Cerón i,1 a Centro de Salud El Palo, Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Investigación del Distrito de Atención Primaria Málaga-Guadalhorce, Departamento de Medicina Preventiva y Salud Pública, Universidad de Málaga, Málaga, Spain b Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Investigación del Distrito de Atención Primaria Málaga-Guadalhorce, Málaga, Spain c Departamento de Psicología Psicología y Trabajo Social, Universidad de Loyola, Sevilla, Spain d Departamento de Personalidad, Evaluación Tratamiento Psicológico, Universidad de Málaga, Málaga, Spain e Centre for Disability Research Policy — Brain Mind Research Institute, Faculty of Health Sciences, University of Sydney, Sydney, Australia f Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona, Spain g Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona, Spain h Institut Universitari d'Investigació en Atenció Primària (IDIAP) Jordi Gol, Barcelona, Spain i Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Investigación del Distrito de Atención Primaria Málaga-Guadalhorce, Málaga, Spain

a r t i c l e

i n f o

Available online xxxx Keywords: Primary prevention Depression Systematic review

a b s t r a c t Objective. To determine the effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression. Methods. Systematic review of systematic reviews and meta-analyses (SR/MA). We searched PubMed, PsycINFO, Cochrane Database of Systematic Reviews, OpenGrey, and PROSPERO from their inception until February 2014. Two reviewers independently evaluated the eligibility criteria of all SR/MA, abstracted data, and determined bias risk (AMSTAR). Results. Twelve SR/MA (156 non-repeated trials and 56,158 participants) were included. Of these, 142 (91%) were randomized-controlled, 13 (8.3%) controlled trials, and 1 (0.6%) had no control group. Five SR/MA focused on children and adolescents, four on specific populations (women after childbirth, of low socioeconomic status, or unfavorable circumstances; patients with severe traumatic physical injuries or stroke) and three addressed the general population. Nine (75%) SR/MA concluded that interventions to prevent depression were effective. Of the 156 trials, 137 (87.8%) reported some kind of effect size calculation. Effect sizes were small in 45 (32.8%), medium in 26 (19.1%), and large in 25 (18.2%) trials; 41 (29.9%) trials were not effective. Of the 141 trials for which follow-up periods were available, only 34 (24.1%) exceeded 12 months. Conclusion. Psychological and/or educational interventions to prevent onset of episodes of depression were effective, although most had small or medium effect sizes. © 2014 Published by Elsevier Inc.

☆ Sources of support: The project has received funding from a Network for Prevention and Health Promotion in Primary Care (redIAPP, RD12/0005) grant and a research project grant (PI12/01914) from the Instituto de Salud Carlos III (Institute of Health Carlos III) of the Ministry of Economy and Competitiveness (Spain), co-financed with European Union ERDF funds. ⁎ Corresponding author at: Departamento de Medicina Preventiva, Facultad de Medicina, Universidad de Málaga, Campus de Teatinos, 29071 Málaga, Spain. Fax: +34 952 137131. E-mail addresses: [email protected] (J.Á. Bellón), [email protected] (P. Moreno-Peral), [email protected] (E. Motrico), [email protected] (A. Rodríguez-Morejón), [email protected] (A. Fernández), [email protected] (A. Serrano-Blanco), [email protected] (E. Zabaleta-del-Olmo), [email protected] (S. Conejo-Cerón). 1 JAB and SCC contributed equally to this work and they are the first authors.

Introduction The 12-month prevalence of DSM-IV major depression in 18 countries from different continents has been reported to range from 2.2 to 10.4% and with a mid-point of 5% (Bromet et al., 2011). Major depression has substantial economic consequences for society (Gustavsson et al., 2011). In 2010 depression ranked fourth in terms of illness burden in western Europe and Australia and fifth in North America (Murray et al., 2012), and it is projected to rank as the greatest contributor in high-income countries by 2030 (Mathers and Loncar, 2006). Despite effective treatments for depression,

http://dx.doi.org/10.1016/j.ypmed.2014.11.003 0091-7435/© 2014 Published by Elsevier Inc.

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

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interventions can only reduce the disease burden by 20% (Chisholm et al., 2004). For all these reasons, interest in the prevention of depression has been growing in the last decade (Muñoz et al., 2010). Hundreds of randomized controlled trials (RCTs), whose aim was to prevent the onset of episodes of depression, have been published, as well as dozens of systematic reviews on this topic (Siontis et al., 2013). Given that such reviews are likely to be of variable quality and scope, the logical and appropriate next step is to conduct a systematic review of the reviews, allowing the findings of separate reviews to be compared and contrasted, thereby providing clinical decision makers with the evidence they need (Smith et al., 2011). The Cochrane Collaboration introduced this new type of Cochrane review in 2009 (Becker and Oxman, 2011), with the aim of providing a summary of evidence at a variety of different levels, including the combination of different interventions, populations, settings, outcomes, conditions, or problems. The objective of the present study was to determine the effectiveness of psychological and/or educational interventions in preventing the onset of episodes of depression in all types of patients, using a systematic review of systematic reviews and meta-analyses (SR/MA). Methods

The search strategy comprised a combination of terms selected from the controlled vocabulary with free-text terms: systematic[sb] AND ((“depressive disorder”[MeSH Terms] OR “depressive disorder” OR depress* OR “depression”[MeSH Terms]) AND prevent* AND (“Health Education”[MeSH] OR psychoeducat* OR educat*) AND (intervention* OR program* OR strateg*)). This strategy was piloted in PubMed and later adapted to PsycINFO, PROSPERO, Cochrane Database of Systematic Reviews, OpenGrey, and PROSPERO. There was no language restriction. The search strategy was performed by two independent researchers (PMP and SCC).

Study selection The records were reviewed for inclusion in 3 phases: first, duplicates were eliminated; then records were selected based on title and abstract, and finally, the full text of candidate articles was read. The entire selection process was performed in duplicate by SCC and PMP, and in case of disagreement a third researcher was consulted to reach consensus (JAB). There was good agreement between the first two reviewers (Kappa index = 0.75; 95% C.I. = 0.49–1.00). Fleiss (1981) characterized kappas over 0.75 as excellent, 0.40 to 0.75 as fair to good, and below 0.40 as poor.

Data collection process

We performed a systematic review of SR/MA on psychological and/or education interventions to prevent the onset of episodes of depression in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) Statement (Moher et al., 2009). The aim of the PRISMA statement, which consists of a 27-item checklist and a 4-phase flow diagram, is to help authors improve the reporting of systematic reviews and meta-analyses. Eligibility criteria Article selection was based on inclusion and exclusion criteria defined specifically for this systematic review (Table 1). The rationale for these inclusion criteria was to have a broad and comprehensive assessment of all preventive interventions in different populations. We focused on psychological and educational interventions because they share the same mechanism of action, facilitating changes in attitudes and behaviors, and because most interventions to prevent depression are of this type. We included only those SR/MA that excluded depressed persons at baseline to separate preventive interventions from treatment of depression. If any of the SR/MA included trials with participants who were diagnosed with depression at baseline, an effect size excluding such trials was required for inclusion in the present systematic review of SR/MA. Information sources and search strategy Five internet-based databases [PubMed, PsycINFO, Cochrane Database of Systematic Reviews, OpenGrey (System for Information on Grey Literature in Europe), and PROSPERO (International Prospective Register of Systematic Reviews)] were searched for articles published from their inception to February 2014. The last search was conducted on February 13, 2014. The reference lists of the articles selected were scrutinized for any additional articles and experts in the field were also contacted to identify additional relevant publications.

We had previously developed a data extraction sheet, tested it with four articles randomly selected from those finally included, and amended it as needed. The main features of these SR/MA were carefully extracted by a single researcher (SCC) and a second researcher (PMP) checked the extracted data. Disagreements were resolved by discussion between both authors; if disagreement remained, a third researcher (JAB) was consulted. The following information was collected for each study selected: authors, year of publication, publication type (systematic review or meta-analysis), number of trials included, total number of participants in each study, type of population based on age and sex, type of prevention (universal, selective, indicated), and summary description of the interventions, intervention providers, comparison, outcome, follow-up periods, and results (Table 2). Universal prevention targets the general population, regardless of risk factors; selective prevention is applied to people with identified risk factors, and indicated that prevention is centered in the population with depressive symptoms but without depression criteria (Weich, 1997).

Assessment of risk of bias The possibility of bias in the systematic reviews and meta-analysis were evaluated by two independent researchers (PMP and SCC) using AMSTAR (Shea et al., 2007). In case of disagreement, a third researcher (JAB) was consulted. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews (Shea et al., 2009). This instrument consists of 11 items assessing independent data extraction, electronic databases consulted, search strategy, included and excluded studies, study characteristics, and other potential biases. The maximum AMSTAR score is 11 for a metaanalysis and 9 for systematic reviews (Table 4). There was good inter-researcher agreement, item by item, between SCC and PMP (Kappa index = 0.84; 95% C.I. = 0.72–0.95).

Table 1 Inclusion and exclusion criteria of systematic reviews and meta-analyses. Criteria

Inclusion criteria

Population Outcome

All types of population None Incidence of depression and/or reducing depressive symptoms SR/M in which the effect on depression and anxiety are measured together (or the effect measures are not given separately) Psychological and/or educational Physical and/or pharmacological therapies

Type of intervention Publication type SR/M Language All languages Design SR/M including trials in which depressed participants at baseline were excluded. Setting All settings

Exclusion criteria

Publications other than SR-M None SR/M including trials in which depressed participants at baseline were not excluded or which do not provide separate results for nondepressed participants at baseline None

SR: systematic review; M: meta-analysis.

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

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Table 2 Excluded articles and reasons for exclusion. Excluded studies Study

Reasons for exclusion

Baraniak A, Sheffield D. The efficacy of psychologically based interventions to improve anxiety, depression and quality of life in COPD: a systematic review and meta-analysis. Patient. Educ. Couns. 2011;83(1):29–36. Siegenthaler E, Munder T, Egger M. Effect of preventive interventions in mentally ill parents on the mental health of the offspring: systematic review and meta-analysis. J. Am. Acad. Child. Adolesc. Psychiatry 2012; 51(1):8–17. Dennis CL, Kingston D. A systematic review of telephone support for women during pregnancy and the early postpartum period. J. Obstet. Gynecol. Neonatal Nurs. 2008;37(3):301–14. Wethington H, Hahn RA, Fuqua-Whitley DS, Sipe TA, Crosby AE, Johnson RL et al., Task Force on Community Preventive Services. The effectiveness of interventions to reduce psychological harm from traumatic events among children and adolescents. A systematic review. Am. J. Prev. Med. 2008;35(3):287–313 Cuijpers P. Prevention: an achievable goal in personalized medicine. Dialogues Clin. Neurosci. 2009;11(4):447–54. Review. Yoshikawa H, Aber JL, Beardslee WR. The effects of poverty on the mental, emotional, and behavioral health of children and youth. Implications for prevention. Am. Psychol. 2012;67(4):272–84. Peñalba V, McGuire H, Leite JR. Psychosocial interventions for prevention of psychological disorders in law enforcement officers (Review). Cochrane Database Syst. 2008 Rev.16, (3) Rose SC, Bisson J, Churchill R, Wessely S. Psychological debriefing for preventing post traumatic stress disorder (PTSD) (Review). Cochrane Database Syst. Rev. 2002 (2) Muñoz RF, Cuijpers P, Smit F, Barrera AZ, Leykin Y. Prevention of major depression. Annu. Rev. Clin. Psychol. 2010;6:181–212. Dennis CL, Dowswell T. Psychosocial and psychological interventions for preventing postpartum depression (Review). Cochrane Database Syst. Rev. 2013:28, 2. Sado M, Ota E, Stickley A, Mori R. Hypnosis during pregnancy, childbirth, and the postnatal period for preventing postnatal depression (Review). Cochrane Database Syst. Rev. 2012:13, 6. Leis JA, Mendelson T, Tandon SD, Perry DF. A systematic review of home-based interventions to prevent and treat postpartum depression. Arch. Womens Ment. Health. 2009:12(1):3–13.

It did not focus on preventing the onset of episodes of depression. It did not focus on preventing the onset of episodes of depression.

Summary measures Effect measures reported in the trials included in the selected SR/MA were as follows: 1) Effect sizes for associations between categorical variables: Relative Risk (RR), Incidence Rate Ratio (IRR) and Odds Ratio (OR) [b 0.4 shows a large prevention effect; 0.40–0.56, medium; and 0.57–0.83, small] (Brownson et al., 1998). 2) Effect sizes based on “variance explained”: Pearson's r [coefficients between 0.10 and 0.29 are small; 0.30–0.50, medium, and N0.50, large] (Cohen, 1988). 3) Effect sizes based on means or distances between means: Cohen's d, Hedges' g, and Standardized Mean Difference (SMD) [effect sizes between 0.20 and 0.49 are small; 0.50–0.80, medium; and N0.8, large] (Cohen, 1988). Risk differences (RD) are differences between control and intervention groups in absolute risk values, and are only comparable between trials when the incidence of depression is similar in the respective control groups. Overlap and subgroup analyses Because primary studies are often included in more than one SR/MA, it is important to describe and quantify this overlap. We constructed a data matrix, placing the primary studies (trials) in rows and the SR/MA in columns (Citation Matrix, in Supplementary Appendix). We calculated the “Corrected Covered Area” (CCA) as a measure of overlap by dividing the frequency of repeated occurrences of the index publication (i.e., the first occurrence of a primary publication) in other reviews by the product of index publications and reviews, reduced by the number of index publications (Pieper et al., 2014). These authors (Pieper et al., 2014) demonstrated the validity and sensitivity to change of the CCA with a sample of 60 systematic reviews of SR/MA, and proposed an interpretation: CCA of 0–5% is slight, 6–10% moderate, 11–15% high, and N 15% very high. Subgroup analyses were performed to further investigate differences between the different SR/MA. In order to assess the direction and magnitude of the effect of overlap bias on effectiveness, specific subgroup analyses (excluding depressed at baseline, type of outcome and population) were implemented with unduplicated trials included in our SR/MA.

Results Study selection As a result of the search strategies (Fig. 1), 241 potentially relevant records were obtained (160 from PubMed, 36 from PsycINFO, 29 from

It did not focus on preventing the onset of episodes of depression. It did not focus on preventing the onset of episodes of depression. It is not a systematic review or meta-analysis It is not a systematic review or meta-analysis Participants non-depressed at baseline were not excluded Participants non-depressed at baseline were not excluded Did not report separate results for those trials that excluded participants depressed at baseline Participants non-depressed at baseline were not excluded (including trials with 20% of depressed patients) Only included one trial Only included one trial on prevention (the other five were trials on treatment)

Cochrane Database of Systematic Reviews, 16 from OpenGrey, and none from PROSPERO). Four additional articles were identified from the reference lists of finally included articles and one after consultation with experts in prevention of depression. Of the 246 records identified, 12 were duplicates (indexed in more than one database) and were excluded. Of the remaining 234 records, 210 were excluded by reviewing title and abstract: 159 did not focus on primary prevention depression, 34 were not systematic review or meta-analyses, and 17 did not focus on psychological and/or educational intervention. Therefore, 24 articles were reviewed in full text. Twelve articles were excluded (Table 2): 4 did not focus on preventing the onset of episodes of depression, 4 included trials that did not provide separate results for participants not depressed at baseline, 2 were not a systematic review or meta-analysis, and 2 included only one prevention trial. The remaining 12 SR/MA were included: (Vázquez et al., 2014; Merry et al., 2011; van der Waerden et al., 2011; Calear and Christensen, 2010; Cuijpers et al., 2008, 2009; De Silva et al., 2009; Kavanagh et al., 2009; Stice et al., 2009; Hackett et al., 2008; Neil and Christensen, 2007; Shaw et al., 2006). Study characteristics Characteristics of the 12 SR/MA included are shown in Table 3. The 12 SR/MA were published between 2006 and 2014, 8 within the last 5 years. Seven (58.4%) were meta-analysis (Hackett et al.,2008; Merry et al., 2011; Cuijpers et al., 2009; Kavanagh et al., 2009; Stice et al., 2009; Cuijpers et al., 2008; van der Waerden et al., 2011) and 5 (41.6%) were systematic reviews (Vázquez et al., 2014; Calear and Christensen, 2010; De Silva et al., 2009; Neil and Christensen, 2007; Shaw et al., 2006). The 12 SR/MA included a total of 232 trials, with some duplications. Of the 37 (23.7%) trials included in more than one study, 12 were included in two, 14 in three, seven in four, three in five and one in six. Discounting this overlap, 156 unduplicated trials and 56,158 participants were included in the present analysis. Of these 156 trials, 142 (91%) were RCTs, 13 (8.3%) were controlled trials without randomization, and one (0.6%) had no control group (pre-post design). The number of trials included in each SR/MA ranged from 2 to 55 (mean = 19.3). Population size ranged from 607 to 16,872 (median =

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

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Identification

4

241 records identified through electronic database

5 additional records identified through other sources

Screening

12 duplicates removed 234 records after removal of duplicates

Eligibility

234 records screened through title and abstract

24 full-text articles assessed for eligibility

210 records excluded: 159 did not focus on primary prevention of depression 34 were not systematic review or meta-analysis 17 did not focus on psychological and/or educational intervention

Included

12 full text articles excluded:

12 systematic reviews and/or meta-analyses included

4 did not focus on primary prevention of depression 4 did not exclude depressed participants at baseline 2 were not systematic review or meta-analysis 2 only included one trial

Fig. 1. Flow-chart of articles excluded and included in the systematic review of systematic reviews and meta-analyses.

4103). Five (41.7%) SR/MA were focused on children and adolescents (Merry et al., 2011; Calear and Christensen, 2010; Kavanagh et al., 2009; Stice et al., 2009; Neil and Christensen, 2007), one (8.3%) were focused on postpartum (Shaw et al., 2006), three (25%) were focused on population with specific risk (van der Waerden et al., 2011; Hackett et al., 2008; De Silva et al., 2009) and three (25%) in all types of population (Vázquez et al., 2014; Cuijpers et al., 2008, 2009). Four SR/MA included trials of selective prevention (van der Waerden et al., 2011; De Silva et al., 2009; Hackett et al., 2008; Shaw et al., 2006); one, universal (Calear and Christensen, 2010); one, indicated (Vázquez et al., 2014); three, universal and indicated (Merry et al., 2011; Kavanagh et al., 2009; Neil and Christensen, 2007); one, selective and indicated (Cuijpers et al., 2009); and two, universal, selective, and indicated (Stice et al., 2009; Cuijpers et al., 2008). The selected SR/MA included no trial that performed universal prevention in adults. Two types of interventions were identified to prevent depression: cognitive behavioral interventions (Behavioral Cognitive Therapy, ‘Coping with depression’, problem solving therapy, social skills training, reducing negative cognitions, and self-help guidelines) and other interventions (interpersonal psychotherapy, counseling, supportive and expressive therapy, life review therapy, motivational interviewing, other psychotherapies, telephone social support, brochures, support groups, contacts with midwives, etc.). Seven SR/MA evaluated both types (Calear and Christensen, 2010; Cuijpers et al., 2008; Vázquez et al., 2014; De Silva et al., 2009; van der Waerden et al., 2011; Neil and Christensen, 2007; Hackett et al., 2008). Four SR/MA evaluated only

cognitive behavioral interventions (Merry et al., 2011; Cuijpers et al., 2009; Kavanagh et al., 2009; Stice et al., 2009) and one included only “other” interventions (Shaw et al., 2006). As for professionals who provided the interventions, we could distinguish four groups: mental health specialists (psychologists, psychiatrists, psychiatric nurses, and therapists), teachers and other school professionals, primary care staff (nurses, midwives, and others) and “other” (social workers, pediatricians, researchers, trained facilitators, and lay persons, including a mother who had experienced both depression and postpartum depression). Interventions were carried out by mental health specialists in 2 SR/MA (Cuijpers et al., 2009; Hackett et al., 2008); educators in one (Calear and Christensen, 2010); mental health specialists and other providers in two (De Silva et al., 2009; Shaw et al., 2006); mental health specialists, educators, and other providers in four (Merry et al., 2011; Stice et al., 2009; Kavanagh et al., 2009; Neil and Christensen, 2007); mental health specialists, primary care staff, and other providers in two (van der Waerden et al., 2011; Cuijpers et al., 2008), and by all types of professionals in one study (Vázquez et al., 2014). Comparison groups in the trials included in the SR/MA were of three types: no intervention or usual care, waiting list, and other interventions (psychotherapy, placebo, counseling, brochures, and any other type of intervention). Six SR/MA had no intervention or usual care as the comparison group (Calear and Christensen, 2010; Cuijpers et al., 2008, 2009; De Silva et al., 2009; Kavanagh et al., 2009; Hackett et al., 2008); one, the waiting list (Neil and Christensen, 2007); two, no intervention

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

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or usual care and other interventions (Merry et al., 2011; Shaw et al., 2006); and three included all type of comparison groups (Vázquez et al., 2014; van der Waerden et al., 2011; Stice et al., 2009). As for the dependent variable being studied, five SR/MA measured depressive symptoms (van der Waerden et al., 2011; De Silva et al., 2009; Kavanagh et al., 2009; Neil and Christensen, 2007; Shaw et al., 2006); three, the incidence of depression (Cuijpers et al., 2008, 2009; Hackett et al., 2008); and four assessed both symptoms and incidence (Merry et al., 2011; Vázquez et al., 2014; Calear and Christensen, 2010; Stice et al., 2009). Seven SR/MA provided follow-up periods for all trials, three had a meta-analysis only for several trials, and two SR/MA did not specify the follow-up period. Of the 141 unduplicated trials for which follow-up periods were provided in the SR/MA, 82 (58.2%) trials had less than 12 months of follow-up, 25 (17.7%) trials had a 12-month follow-up, and 34 (24.1%) longer than 12 months. Table 4 shows the risk of bias for each study. In the seven metaanalysis, the mean was 8.43 (SD = 1.69; range 6–10) for a maximum score of 11. In the five systematic reviews, the mean was 5.8 (SD = 2.3; range 3–9) for a maximum score of 9. Only two SR/MA were below 50% of the quality score (Shaw et al., 2006; Vázquez et al., 2014), three between 50% and 55% (Cuijpers et al., 2009; Kavanagh et al., 2009; Calear and Christensen, 2010), and six over 73% (Neil and Christensen, 2007; Cuijpers et al., 2008; Stice et al., 2009; van der Waerden et al., 2011; Merry et al., 2011; De Silva et al., 2009). Effectiveness of the interventions Children and adolescents Five SR/MA were conducted in children and adolescents. One systematic review that included 55 trials (Merry et al., 2011) concluded that the risk of having a depressive disorder post-intervention was reduced at 3, 9, and 12 months; however, there was no evidence of effectiveness at 24 and 36 months. Another systematic review that included 46 trials (Stice et al., 2009) found small average effect sizes to reduce depressive symptoms in both post-test (r = 0.15) and follow-up (r = 0.11). A systematic review that included 21 trials (17 universal, 4 indicated) conducted in Australia (Neil and Christensen, 2007) found statistically significant results for 10 universal prevention trials (Cohen's d range = 0.21–0.82), but not in seven others; for indicated prevention, two trials had statistically significant results (Cohen's d range = 0.55 = 0.96) and two did not. One meta-analysis of cognitive behavioral interventions (Kavanagh et al., 2009) found a statistically significant reduction of depressive symptoms in the combined results of 13 trials, both at 1 month (SMD = −0.16) and 3 months (SMD = − 0.21) follow-up. However, these differences were not statistically significant at 6 months (SMD = −0.12) and 12 months (SMD = − 0.08). The most recent systematic review (Calear and Christensen, 2010) included three universal prevention trials; at 6 and 24 months, one of them had Cohen's d = 0.27 and 0.51 respectively, while in the other two the range was −0.12 to 0.10. The overlap of trials among these five SR/MA was between moderate and high (CCA = 11%). Postpartum The systematic review by Shaw et al. (2006) included 28 trials, of which 10 measured postpartum depression and three found a statistically significant reduction of depressive symptoms. Population with specific risk A meta-analysis (10 trials) studied prevention of depression in women with low socioeconomic status or unfavorable circumstances, the combined Hedges' g was 0.36 (95% CI: 0.21 − 0.51) (van der Waerden et al., 2011). Another meta-analysis (2 trials) with patients who suffered stroke (Hackett et al., 2008) found an OR = 0.64 (95% CI: 0.42 − 0.98). In a systematic review of five trials in patients with severe traumatic injuries (De Silva et al., 2009), only one trial found statistically

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significant results. There was no overlap of trials among these three SR/MA. All types of population Three SR/MA included trials with all types of population. A metaanalysis (Cuijpers et al., 2009) on the topic “coping with depression” interventions (6 trials) found an IRR = 0.62 (95% CI: 0.43 − 0.91). Another meta-analysis included 15 trials that excluded depressed patients at baseline (Cuijpers et al., 2008), and the IRR was 0.78 (95% CI: 0.65–0.93). Finally, in a systematic review (42 trials), approximately 70% of the trials found statistically significant results to reduce depressive symptoms, although the effect sizes were small (b 0.50) (Vázquez et al., 2014). The overlap of trials among these three SR/MA was very high (CCA = 16.7%). Global effectiveness Of the 12 SR/MA, 9 (75%) concluded that psychological and/or educational interventions to prevent depression were effective (Vázquez et al., 2014; Merry et al., 2011; van der Waerden et al., 2011; Cuijpers et al., 2008, 2009; Kavanagh et al., 2009; Stice et al., 2009; Hackett et al., 2008; Neil and Christensen, 2007). The systematic review by Calear and Christensen (2010) showed contradictory results and reviews by Shaw et al. (2006), De Silva et al. (2009) clearly found no effectiveness. Of the 156 unduplicated trials included in our systematic review of SR/MA, 124 (79.5%) measured reduction of depressive symptoms as outcome. Of these, 52 (41.9%) found statistically significant results, although many lacked statistical power due to sample size. We found that in 54 (34.6%) trials, depressed patients were not excluded at baseline and the relevant information was not available in 22 (14.1%). In 137 (87.8%) unduplicated trials, some analyses of effect size were reported in the SR/MA we analyzed. Of these, 41 (29.9%) trials found that the intervention was not effective, and observed that effect size was small in 45 (32.8%) trials, medium in 26 (19.1%), and large in 25 (18.2%). Of these 137 trials, only 31 (22.6%) trials reported incidence of depression as an outcome and 106 (77.4%) reported reduction of symptoms. Most trials, 99 (72.3%), were implemented in children and/or adolescents (Table 5). Subgroup analyses showed that effectiveness was higher in trials that were performed in adults with subthreshold depression, those that analyzed incidence of depression, and those that excluded depressed patients at baseline; it was also slightly higher in trials that used a clinical interview compared to a symptoms scale for excluding depressed patients at baseline (Table 5). Discussion Main findings This systematic review of SR/MA found a small-to-medium preventive effect of psychological and educational interventions to prevent the onset of episodes of depression. Although some questions remain unanswered (long-term effectiveness, cost-effectiveness, superiority among different interventions, etc.), it can be concluded that depression is preventable. Strengths and limitations These findings, derived from 12 SR/MA that included 156 unduplicated trials, were based on a large and heterogeneous population: 56,158 participants from different types of populations and settings. A wide range of psychological and/or educational interventions to prevent the onset of episodes of depression was described in these 12 SR/MA. Therefore, our results are quite generalizable and provide an external validity exceeding that of any one of the SR/MA included in the present study. Almost 70% of the SR/MA included in our systematic review have been conducted in the past five years, so our results are based on relatively current SR/MA. This is important because many trials have been published in recent years on preventing depression (Vázquez

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

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Type of Intervention a prevention

Authors — year

Type of study

Total sample (included trials)

Population

Vázquez et al. (2014)

Systematic review

10,544 (42 trials)

Children, Indicated adolescents, adults, elderly, pregnant, non-professional caregivers

De Silva et al. (2009)

Systematic review

756 (5 trials)

Patients with severe traumatic injuries

Selective

Merry et al. (2011)

Meta-analysis

14,406 (55 trials)

Children and Adolescents

Universal and indicated

van der Waerden et al. (2011)

Meta-analysis

816 (10 trials)

Women with low socioeconomic status or unfavorable circumstances

Selective

Intervention provider

CWD, IT, PST, PRP; TKC, Bibliotherapy Mind Over Mood; SET; LRT; CATCH-IT; ACT

Psychologists, professional social areas; staff senior centers, mental health nurses, therapists, professional or paraprofessional of educational areas, the participants themselves BCT, IT, counseling, Health professional self-help, (psychologist, medical brochure, practitioner, nurse or collaborative occupational therapist); intervention lay person BCT, self-efficacy, Clinician (graduate level stress reduction, students of psychology, optimism psychiatric nurses, school counselors, psychologist); teachers; trained facilitators

BCT, IT, social support and psychoeducation, telephone social support and psychoeducation

Mental health professionals (psychologists, psychiatric nurses or counselors); nurses; trained non-professionals

Comparison

Outcome

Follow-up

Results b

Usual care; waiting list, no intervention, placebo, minimal interventions

Depressive symptoms and incidence of depression

3 to 36 months 24 b 12 months 5 = 12 months 3 N 12 months ⁎10 trials did not provide follow-up data

Approximately 70% of the trials found statistically significant results with small effect sizes (b0.50) to reduce depressive symptoms. Only 24 trials gave data on incidence of depression and theses were contradictory.

Usual care

Depressive symptoms

3 to 12 months 4 b 12 months 1 = 12 months 0 N 12 months

Placebo, any intervention or no intervention

Depressive symptoms and Incidence of depression

3 to more than 36 months 34 b 12 months 9 = 12 months 12 N 12 months

Usual care, waiting list, psychoeducation, no intervention

Depressive symptoms

1 to 24 months 2 b 12 months 3 = 12 months 1 N 12 months ⁎4 trials did not provide follow-up data

Only one of the 5 trials obtained significant results: at 1 month: effect size = 0.58, p = 0.07; at 4 months: effect size = 1.15, p b 0.05 (at 4 months) Compared with no intervention: Post-test: SMD −0.20 (95% CI −0.26 to −0.14); 3–9 months: SMD −0.16 (95% CI −0.23 to −0.10); 12 months: SMD −0.10 (95% CI −0.18 to −0.02) Compared with placebo: Post-test: SMD −0.05 (95% CI −0.21 to 0.11); 3–9 months: SMD 0.07 (95% CI −0.12 to 0.26); 12 months: SMD −0.07 (95% CI −0.30 to 0.16); 24 months: SMD −0.05 (95% CI −0.29 to 0.19) Compared with no intervention: Post-test: RD −0.09 (95% CI −0.14 to −0.05); 3 months: RD −0.11(95% CI −0.16 to −0.06); 12 months: RD −0.06 (95% CI −0.11 to −0.01); 24 months: RD −0.01 (95% CI −0.04 to 0.03); 36 months: RD −0.10 (95% CI −0.19 to −0.02) Compared with placebo: Post-test: RD −0.07 (95% CI −0.19 to 0.04); no studies with follow-up. Hedge's g: 0.36 (95% CI 0.21 to 0.51)

J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

Table 3 Details of studies included in the systematic review of systematic reviews and meta-analyses.

Systematic review

2,821 (3 trials)

Children (11–14 years) and adolescents (13–19 years)

Universal

BCT, IT

Teacher; graduate student/intern + teachers

No intervention

Depressive symptoms and Incidence of depression

18 to 48 months 0 b 12 months 0 = 12 months 3 N 12 months

Cuijpers et al. (2009)

Meta-analysis

724 (6 trials)

Selective and indicated

CWD

Therapist

Usual care

Incidence of depression

6 to 24 months 0 b 12 months 3 = 12 months 3 N 12 months

Kavanagh et al. (2009)

Meta-analysis

5,385 (17 trials)

Adolescents, adults (18–65 years), pregnant and patients with specific physical diseases Young people (11–19 years)

Universal and indicated

BCT

School staff; psychologist; researcher

No intervention

Depressive symptoms

3 to 36 months ⁎17 trials did not provide follow-up data

Stice et al. (2009)

Meta-analysis

16,872 (46 trials)

Children and Adolescents

Universal, selective and indicated

Negative cognitions reduction, PST, and social skills training

Professional interventionist; teacher; school nurse; counselor

Usual care, waiting list, advice

Depressive symptoms and Incidence of depression

Cuijpers et al. (2008)

Meta-analysis

2,272 (15 trials)

Universal, selective and indicated

BCT, IT, and other type of interventions

Mental health professionals and other providers

Usual care

Incidence of depression

Hackett et al. (2008)

Meta-analysis

607 (2 trials)

Selective

Usual care

Incidence of depression

Systematic review

12,418c (21 trials)

PST, HBT, motivational interviewing BCT, IT, psychoeducation

Specialist nurses; mixed team of therapists

Neil and Christensen (2007)

Children, Adolescents, pregnant and postpartum women, patients with specific physical diseases Patients suffering from stroke. Adolescents

3 to 36 months 15 b 12 months 7 = 12 months 9 N 12 months ⁎15 trials did not provide follow-up data 3 to 36 months 5 b 12 months 5 = 12 months 5 N 12 months

Teacher; researcher; psychologist

Waiting list

Depressive symptoms

Shaw et al. (2006)

Systematic review

14,436 (10 trials)

Nurse home visits, conference care, telephone support, standardized debriefing session, self-help manual and support group invitation

Public health nurse; mother who had previously experienced postpartum depression; trained midwives; health visitor; social worker; nurse practitioner

Usual care, usual information, brochure

Depressive symptoms

Postpartum women

Universal and indicated

Selective

⁎2 trials did not provide follow-up data 4 to 48 months ⁎21 trials did not provided follow-up data

0.5 to 6 months 10 b 12 months 0 = 12 months 0 N 12 months

Post-test: one trial Cohen's d = 0.36, and the other two Cohen's d 0.02 and 0.14 respectively; At the follow-up: one trial Cohen's d were 0.27 and 0.51; the other two trials Cohen's d ranged −0.12 to 0.10 IRR 0.62 (95% CI: 0.43 to 0.91)

At 1 month: SMD − 0.16 (95% CI −0.26 to −0.05); at 3 months: SMD −0.21 (95% CI −0.35 to −0.07); at 6 months: SMD −0.12 (95% CI −0.26 to 0.02); at 12 months: SMD −0.08 (95% CI −0.18 to 0.03) r = 0.15 for average post-test and r = 0.11 for average follow-up

IRR 0.78 (95% CI 0.64 to 0.95)

OR 0.64 (95% CI 0.42 to 0.98)

Universal prevention: Cohen's d range = 0.21–0.82 (10 trials were statistically significant and 7 did not) Indicated prevention: 2 were statistically significant and 2 did not There was statistically significant results to reduce depressive symptoms in 3 from 10 trials

J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

Calear and Christensen (2010)

a BCT: Behavioral Cognitive Therapy; IT: Interpersonal Therapy; PST: Problem Solving Therapy; HBT: Home-Based Therapy; CWD: Coping with Depression; PRP: Penn Resiliency Program; TKC: Teaching Kids to Cope; SET: Supportive and Expressive Therapy; LRT: Life Review Therapy; CATCH-IT: Competent Adulthood Transition with Cognitive-Behavioral and Interpersonal Training; ACT: Acceptance and Commitment Therapy. b RD: Risk Difference; OR: Odds Ratio; IRR: Incidence Rate Ratio; SMD: Standardized Mean Difference; r: Pearson's r.; CI: confidence interval. c This review only provided the sample size of the intervention group (we have calculated the total sample multiplying by 2).

7

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J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

et al., 2014). Although two SR/MA had lower quality (risk of bias according to AMSTAR), the findings of our study are derived from SR/MA with good quality, and 90% of the included trials were randomized controlled trials (although the quality of the individual trials must be taken into consideration). Our study also has several limitations. Some trials were included more than once in the selected SR/MA, which could have skewed some results. However, we found that the overall overlap of trials among SR/ MA was slight, CCA of 4.5% (Pieper et al., 2014). To better understand and minimize this bias, especially when measuring effectiveness, we analyzed the available information from the 156 unduplicated trials. Both conclusions about the effectiveness, from the systematic review of SR/ MA and from all unduplicated trials, were similar. Despite our criterion requiring exclusion of SR/MA that included patients diagnosed with depression at baseline, we found that 34% of trials included such patients. The subgroup analysis showed that excluding these trials yielded higher effectiveness (Table 5); in other words, interventions to prevent depression were less effective in depressed patients. Therefore, most trials and SR/MA that included depressed patients at baseline underestimated the effectiveness of interventions to prevent depression, Nonetheless, using secondary sources of information, we assumed that all types of biases were cumulated at two levels: from the trials (level 1) and from systematic reviews and/or meta-analysis (level 2). We excluded more meta-analyses than systematic reviews because the latter made it easier to separate out trials that excluded depressed patients at baseline. This was not possible in a meta-analysis unless effect size values were separately reported for trials with non-depressed patients at baseline (Cuijpers et al., 2008). Despite this, our study included more meta-analyses than systematic reviews. Regarding publication bias, we reviewed OpenGrey, obtaining 16 documents that did not meet our inclusion criteria; however, OpenGrey is limited to European grey literature. In addition, the international registry of systematic reviews (PROSPERO) was consulted to find SR/MA registered and unpublished or registered and still being developed. No study was found, although the registration of systematic reviews and meta-analysis is still infrequent.

Detailed discussion based on the results In postpartum women, no evidence of intervention effectiveness was found in the only systematic review of this topic (Shaw et al., 2006) included in our study. However, this review had low quality. The recent study by Dennis and Dowswell (2013) reached the opposite conclusion, but was not included in our study because they reviewed trials with participants who were depressed at baseline. Selective prevention was the most widely used type of intervention in our study. It seems logical to intervene in people at higher risk, and thus most in need, as a priority. Moreover, from a more pragmatic point of view, evaluating effectiveness in high-risk populations has lower sample-size requirements. Furthermore, intervening in a selective population offers the opportunity to tailor the intervention to the specific risk factor, although in general this has not been done. We cannot conclude that selective prevention was or was not effective; rather, the findings should be limited to the specific risk assessed and further inferences about selective populations cannot be generalized. From this perspective, psychological and educational interventions were effective (small effect size) in women with low socioeconomic status and patients who suffered stroke but not in patients with severe physical trauma injuries. The subgroup analysis from unduplicated trials showed higher effectiveness in adults with subthreshold depression (Table 5); however, we should be careful with this conclusion, as there may be some type of confounding bias. This difference could be explained by a third variable, such as type of intervention or the trials' risk of bias.

Only three SR/MA (Cuijpers et al., 2008, 2009; Vázquez et al., 2014) were carried out with all patient types, but only one of them, with 15 trials that excluded depressed paitents at baseline (Cuijpers et al., 2008), included all types of prevention and interventions. Consequently, more SR/MA of this type are needed to generate a more conclusive understanding of the overall effectiveness of preventing depression. From this point of view, our systematic review of SR/MA contributes new evidence. The overlap of trials among these three SR/MA was very high (CCA = 16.7%), and so their joint interpretation raises doubts. There was great interest in the prevention of depression in children and adolescents (5 of 12 SR/MA and 99 of 137 unduplicated trials that reported effect sizes). Possible explanations are that prevention of onset of depression at an early age might have a greater impact (Clark et al., 2007), educators are readily available as providers of the interventions, children and adolescents are a very accessible target population at school, and/or that the skills to prevent depression should be learned and taught in an educational context. However, trials that evaluated the prevention of depression in children and adolescents found that interventions were effective only in the short-term, while long-term effectiveness is questionable. Of these 5 SR/MA, Merry's systematic review had higher quality and included more trials. The overlap among these 5 SR/MA was moderate–high (CCA = 11%); therefore their joint findings should be interpreted with caution. Regarding the type of intervention, there was great heterogeneity, although the cognitive-behavioral approach was most frequently used. One explanation could be that a large number of trials found the cognitive-behavioral therapy effective in the treatment of depression (Cuijpers et al., 2013); it seems logical that it should work in prevention as well. However, the effect size of this type of intervention was only small or medium, including specific SR/MA on “coping with depression” (Cuijpers et al., 2009) and school-based cognitive-behavioral interventions (Kavanagh et al., 2009). Within the cognitive-behavioral orientation, interventions were very heterogeneous and mostly of low intensity. From the data collected in our study, we cannot conclude anything about the superiority of one type of intervention over another, as most of the trials used as a comparator “no intervention, usual care or waiting list”. Most of the SR/MA included interventions that were provided by mental health specialists, to a lesser extent by educators, more sparsely by lay persons, and occasionally by primary care professionals. It seems reasonable that formal psychological interventions were conducted by mental health specialists; however, since patients in primary prevention are not ill, it would be desirable to develop and evaluate preventive interventions that can be implemented by non-specialists in mental health, by other non-health professionals, and even better by the patients themselves. To measure the incidence of depression, rather than depressive symptoms, much larger sample sizes are required; this could explain why less than half of the SR/MA or only 23% of the unduplicated trials reported incidence of depression. The effectiveness was higher in those trials that assessed incidence of depression (Table 5), although this could be related to other variables (e.g. type of intervention and population, sample size or methodological quality of the trial). From our data, we cannot draw conclusions about the greater effectiveness of any specific type of prevention (universal, selective or indicated). A reasonable option would be to provide personalized prevention, fitting the type and intensity of intervention to the level of overall risk of depression and type of risk factors present in a given patient (King et al., 2008; Bellón et al., 2011, 2013). Only 24% of the trials had a follow-up period longer than 12 months, and as we have pointed out, there is a lack of evidence about long-term effectiveness. The findings of one meta-regression analysis (Cuijpers et al., 2008) indicated that follow-up periods were inversely related to incidence rate ratios, which may mean that prevention efforts delay the onset of depression disorders rather than preventing them altogether.

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

First author (year)

1. Was an “a priori” design provided?

2. Was there duplicate study selection and data extraction?

3. Was a comprehensive literature search performed?

4. Was the status of publication (i.e., grey literature) used as an inclusion criterion?

5. Was a list of studies (included and excluded) provided?

6. Were characteristics of included studies provided?

7. Was the scientific quality of the included studies assessed and documented?

8. Was the scientific quality of the included studies used appropriately in formulating conclusions?

9. Were the methods used to combine the findings of studies appropriate?

10. Was the likelihood of publication bias assessed?

11. Were potential conflicts of interest included?

Total score

Percent

Vázquez et al. (2014) De Silva et al. (2009) Merry et al. (2011) van der Waerden et al. (2011) Calear and Christensen (2010) Cuijpers et al. (2009) Kavanagh et al. (2009) Stice et al. (2009) Cuijpers et al. (2008) Neil and Christensen (2007) Shaw et al. (2006)

+

−

+

−

−

+

−

−

NA

NA

−

3/9

33.3%

+

+

+

+

+

+

+

+

NA

NA

+

9/9

100%

+

+

+

+

+

+

+

+

+

+

+

11/11 100%

+

+

+

+

−

+

+

+

+

+

+

10/11 90.9%

+

−

+

−

−

+

+

+

NA

NA

−

5/9

55.6%

+

−

+

−

+

+

+

−

+

−

−

6/11

54.5%

+

+

−

+

−

−

+

+

+

−

−

6/11

54.5%

+

+

+

+

−

+

+

+

+

−

−

8/11

72.7%

+

−

+

+

−

+

+

+

+

+

+

9/11

81.8%

+

+

+

+

−

+

+

+

NA

NA

+

8/9

88.9%

−

−

+

−

−

+

+

+

NA

NA

−

4/9

44.4%

J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003

Table 4 Risk of bias of the systematic reviews and/or meta-analyses.

NA: not applicable.

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J.Á. Bellón et al. / Preventive Medicine xxx (2014) xxx–xxx

Table 5 Effectiveness (effect sizes) to prevent depression according to different subgroups of non-repeated trials included in the systematic review of systematic reviews and meta-analyses.

Effect size available Excluding depressed at baseline Yes No Information not available Excluding depressed at baseline by diagnostic interview by symptoms scales Information not available Outcomesa Incidence of depression Reduction of symptoms Type of population Childhood/adolescence Postpartum women Adults with subthreshold depression Adults with other risks of depression

Number of trials

No effectiveness

Small

Medium

Large

137

41 (29.9%)

45 (32.8%)

26 (19.1%)

25 (18.2%)

72 46 19

18 (25.0%) 17 (37.0%) 9 (42.1%)

18 (25.0%) 14 (30.4%) 12 (57.9%)

20 (27.8%) 8 (17.4%) –

16 (22.2%) 7 (15.2%) –

35 35 2

9 (25.6%) 5 (14.2%) 2 (100%)

8 (22.9%) 12 (34.3%) –

8 (22.9%) 10 (28.6%) –

10 (28.6%) 8 (22.9%) –

31 106

4 (12.9%) 37 (34.9%)

8 (25.8%) 37 (34.9%)

9 (29.0%) 17 (16.0%)

10 (32.3%) 15 (14.2%)

99 13 15 10

18 (18.3%) 6 (46.1%) 3 (20.0%) 2 (20.0%)

28 (28.3%) 3 (23.1%) 2 (13.3%) 4 (40.0%)

15 (15.2%) 1 (7.7%) 4 (26.7%) 3 (30.0%)

15 (15.2%) 3 (23.1%) 6 (40.0%) 1 (10.0%)

a Several trials reported both outcomes, incidence of depression and reduction of symptoms. In these cases, the trials were classified into the only category showing statistically significant results, as incidence of depression if both categories were significant, and as reduction of symptoms if both outcomes were nonsignificant.

Practical implications and future research lines

Authors' information

From a systematic review of SR/MA, we synthesized and compared the findings of 12 SR/MA whose specific objective was to determine the effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression. We also conducted subgroup analyses and have determined the reasons for conflicting results. By identifying the reasons for discordance, users (including clinicians, Health Technology Agencies, policy-makers, researchers and patients, depending on the context) are able to base their decisions on the most current, reliable, and suitable data for their situation (Cooper and Koenka, 2012; Pieper et al., 2012). The main conclusion of our systematic review of SR/MA is that psychological and educational interventions were effective to prevent depression. Therefore, it is to be expected that the development and implementation of preventing programs will contribute to reducing the burden of depression. In general, effect sizes of preventive interventions are usually small or moderate, such as in primary prevention of cardiovascular diseases (Tonelli et al., 2011; Estruch et al., 2013). However, population prevention programs often have a large impact on health and tend to be cost-effective when interventions are simple and inexpensive. There is an urgent need to know whether programs to prevent depression have good indexes of costeffectiveness and cost-utility (Mihalopoulos et al., 2011). Some of the questions that remain unanswered are the following: what are the most effective interventions? What type of population should be a priority for prevention of depression? What are the best strategies to prevent depression? Universal, selective, or/and indicated prevention? Personalized and stepped prevention? Another reasonable option would be to develop and evaluate new interventions to increase effectiveness and/or to decrease costs (Buntrock et al., 2014). Furthermore, trials with longer follow-up and large sample sizes are also needed. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ypmed.2014.11.003.

All of these authors are members of the Spanish Network of Primary Care Research (redIAPP), which is financed by the Institute of Health Carlos III (ISCIII): JAB, SCC, PMP, EM and ARM from the Mental Health, Services and Primary Care (SAMSERAP) group in Malaga; EZ from the Services Research group in Barcelona; and AF and ASB from the Mental Health (SJD) group in Barcelona.

Authors' contributions JAB had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. JAB, SCC and PMP designed the study and the other authors collaborated on the design. JAB, SCC and PMP performed the search and selection of studies and the data analysis and the other authors collaborated on designing the strategy. JAB, SCC and PMP drafted the paper and all authors discussed and agreed upon the final version.

Conflict of interest statement The authors declare that there are no conflicts of interests.

Acknowledgments The authors thank the Primary Care District of Malaga, particularly Maximiliano Vilaseca, for their support. We also thank the Institute of Health Carlos III (ISCIII), The Institute of Biomedical Research of Málaga (IBIMA), (C-02) and Boni Bolíbar and the Network for Prevention and Health Promotion in Primary Care (RD12/0005) (redIAPP) for their economic and logistical support. References Becker, L., Oxman, A.D., 2011. Overviews of reviews. In: Higgins, J.P.T., Green, S. (Eds.), Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, Oxford (Available from www.cochranehandbook.org). Bellón, J.A., Luna, J.D., King, M., et al., 2011. Predicting the onset of major depression in primary care: international validation of a risk prediction algorithm from Spain. Psychol. Med. 41 (10), 2075–2088. Bellón, J.A., Conejo-Cerón, S., Moreno-Peral, P., et al., 2013. Preventing the onset of major depression based on the level and profile of risk of primary care attendees: protocol of a cluster randomised trial (the predictD-CCRT study). BMC Psychiatry 13, 171. Bromet, E., Andrade, L.H., Hwang, I., et al., 2011. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 9, 90. Brownson, R.C., Remington, P.I., Davis, J.R. (Eds.), 1998. Chronic Disease Epidemiology and Control, 2nd ed. American Public Health Association, Washington DC. Buntrock, C., Ebert, D.D., Lehr, D., et al., 2014. Evaluating the efficacy and costeffectiveness of web-based indicated prevention of major depression: design of a randomised controlled trial. BMC Psychiatry 14, 25 (Jan 31). Calear, L., Christensen, H., 2010. Systematic review of school-based prevention and early intervention programs for depression. J. Adolesc. 33, 429–438. Chisholm, D., Sanderson, K., Ayuso-Mateos, J.L., Saena, S., 2004. Reducing the global burden of depression: population-level analysis of intervention cost effectiveness in 14 world regions. Br. J. Psychiatry 184, 393–403. Clark, C., Rodgers, B., Caldwell, T., Power, C., Stansfeld, S., 2007. Childhood and adulthood psychological ill health as predictors of midlife affective and anxiety disorders: the 1958 British Birth Cohort. Arch. Gen. Psychiatry 64 (6), 668–678. Cohen, Jacob, 1988. Statistical Power Analysis for the Behavioral Sciences, Second ed. Erlbaum, Hillsdale, NJ.

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Please cite this article as: Bellón, J.Á., et al., Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses, Prev. Med. (2014), http://dx.doi.org/10.1016/j.ypmed.2014.11.003