Second-generation antidepressants for preventing seasonal affective disorder in adults.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Light therapy for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery and form of light vary. OBJECTIVES: To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non-randomised studies. We intended to include studies that compared any type of light therapy (e.g. bright white light, administered by visors or light boxes, infrared light, dawn stimulation) versus no treatment/placebo, second-generation antidepressants, psychological therapies, melatonin, agomelatine, lifestyle changes, negative ion generators or another of the aforementioned light therapies. We also planned to include studies that looked at light therapy in combination with any comparator intervention. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications, independently abstracted data and assessed risk of bias of included studies. MAIN RESULTS: We identified 3745 citations after de-duplication of search results. We excluded 3619 records during title and abstract review. We assessed 126 full-text papers for inclusion in the review, but only one study providing data from 46 people met our eligibility criteria. The included RCT had methodological limitations. We rated it as having high risk of performance and detection bias because of lack of blinding, and as having high risk of attrition bias because study authors did not report reasons for dropouts and did not integrate data from dropouts into the analysis.The included RCT compared preventive use of bright white light (2500 lux via visors), infrared light (0.18 lux via visors) and no light treatment. Overall, white light and infrared light therapy reduced the incidence of SAD numerically compared with no light therapy. In all, 43% (6/14) of participants in the bright light group developed SAD, as well as 33% (5/15) in the infrared light group and 67% (6/9) in the non-treatment group. Bright light therapy reduced the risk of SAD incidence by 36%; however, the 95% confidence interval (CI) was very broad and included both possible effect sizes in favour of bright light therapy and those in favour of no light therapy (risk ratio (RR) 0.64, 95% CI 0.30 to 1.38; 23 participants, very low-quality evidence). Infrared light reduced the risk of SAD by 50% compared with no light therapy, but the CI was also too broad to allow precise estimations of effect size (RR 0.50, 95% CI 0.21 to 1.17; 24 participants, very low-quality evidence). Comparison of both forms of preventive light therapy versus each other yielded similar rates of incidence of depressive episodes in both groups (RR 1.29, 95% CI 0.50 to 3.28; 29 participants, very low-quality evidence). Reasons for downgrading evidence quality included high risk of bias of the included study, imprecision and other limitations, such as self-rating of outcomes, lack of checking of compliance throughout the study duration and insufficient reporting of participant characteristics.Investigators provided no information on adverse events. We could find no studies that compared light therapy versus other interventions of interest such as second-generation antidepressants, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Evidence on light therapy as preventive treatment for people with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.

Psychological therapies for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on psychological therapies as preventive interventions. OBJECTIVES: To assess the efficacy and safety of psychological therapies (in comparison with no treatment, other types of psychological therapy, second-generation antidepressants, light therapy, melatonin or agomelatine or lifestyle interventions) in preventing SAD and improving person-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared psychological therapy versus no treatment, or any other type of psychological therapy, light therapy, second-generation antidepressants, melatonin, agomelatine or lifestyle changes. We also planned to compare psychological therapy in combination with any of the comparator interventions listed above versus no treatment or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria, independently extracted data, assessed risk of bias, and graded the certainty of evidence. MAIN RESULTS: We identified 3745 citations through electronic searches and reviews of reference lists after deduplication of search results. We excluded 3619 records during title and abstract review and assessed 126 articles at full-text review for eligibility. We included one controlled study enrolling 46 participants. We rated this RCT at high risk for performance and detection bias due to a lack of blinding.The included RCT compared preventive use of mindfulness-based cognitive therapy (MBCT) with treatment as usual (TAU) in participants with a history of SAD. MBCT was administered in spring in eight weekly individual 45- to 60-minute sessions. In the TAU group participants did not receive any preventive treatment but were invited to start light therapy as first depressive symptoms occurred. Both groups were assessed weekly for occurrence of a new depressive episode measured with the Inventory of Depressive Syptomatology-Self-Report (IDS-SR, range 0-90) from September 2011 to mid-April 2012. The incidence of a new depressive episode in the upcoming winter was similar in both groups. In the MBCT group 65% of 23 participants developed depression (IDS-SR ≥ 20), compared to 74% of 23 people in the TAU group (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.30; 46 participants; very low quality-evidence).For participants with depressive episodes, severity of depression was comparable between groups. Participants in the MBCT group had a mean score of 26.5 (SD 7.0) on the IDS-SR, and TAU participants a mean score of 25.3 (SD 6.3) (mean difference (MD) 1.20, 95% CI -3.44 to 5.84; 32 participants; very low quality-evidence).The overall discontinuation rate was similar too, with 17% discontinuing in the MBCT group and 13% in the TAU group (RR 1.33, 95% CI 0.34 to 5.30; 46 participants; very low quality-evidence).Reasons for downgrading the quality of evidence included high risk of bias of the included study and imprecision.Investigators provided no information on adverse events. We could not find any studies that compared psychological therapy with other interventions of interest such as second-generation antidepressants, light therapy, melatonin or agomelatine. AUTHORS' CONCLUSIONS: The evidence on psychological therapies to prevent the onset of a new depressive episode in people with a history of SAD is inconclusive. We identified only one study including 46 participants focusing on one type of psychological therapy. Methodological limitations and the small sample size preclude us from drawing a conclusion on benefits and harms of MBCT as a preventive intervention for SAD. Given that there is no comparative evidence for psychological therapy versus other preventive options, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences and other preventive interventions that are supported by evidence.

Melatonin and agomelatine for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly starts in autumn or winter and remits in spring. The prevalence of SAD depends on latitude and ranges from 1.5% to 9%. The predictable seasonal aspect of SAD provides a promising opportunity for prevention in people who have a history of SAD. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions. OBJECTIVES: To assess the efficacy and safety of agomelatine and melatonin (in comparison with each other, placebo, second-generation antidepressants, light therapy, psychological therapy or lifestyle interventions) in preventing SAD and improving person-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we intended also to include non-randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second-generation antidepressant, light therapy, psychological therapies or lifestyle changes. We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions mentioned above versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications, abstracted data and assessed risk of bias of included studies independently. We intended to pool data in a meta-analysis using a random-effects model, but included only one study. MAIN RESULTS: We identified 3745 citations through electronic searches and reviews of reference lists after deduplication of search results. We excluded 3619 records during title and abstract review and assessed 126 full-text papers for inclusion in the review. Only one study, providing data of 225 participants, met our eligibility criteria and compared agomelatine (25 mg/day) with placebo. We rated it as having high risk of attrition bias because nearly half of the participants left the study before completion. We rated the certainty of the evidence as very low for all outcomes, because of high risk of bias, indirectness, and imprecision.The main analysis based on data of 199 participants rendered an indeterminate result with wide confidence intervals (CIs) that may encompass both a relevant reduction as well as a relevant increase of SAD incidence by agomelatine (risk ratio (RR) 0.83, 95% CI 0.51 to 1.34; 199 participants; very low-certainty evidence). Also the severity of SAD may be similar in both groups at the end of the study with a mean SIGH-SAD (Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders) score of 8.3 (standard deviation (SD) 9.4) in the agomelatine group and 10.1 (SD 10.6) in the placebo group (mean difference (MD) -1.80, 95% CI -4.58 to 0.98; 199 participants; very low-certainty evidence). The incidence of adverse events and serious adverse events may be similar in both groups. In the agomelatine group, 64 out of 112 participants experienced at least one adverse event, while 61 out of 113 did in the placebo group (RR 1.06, 95% CI 0.84 to 1.34; 225 participants; very low-certainty evidence). Three out of 112 patients experienced serious adverse events in the agomelatine group, compared to 4 out of 113 in the placebo group (RR 0.76, 95% CI 0.17 to 3.30; 225 participants; very low-certainty evidence).No data on quality of life or interpersonal functioning were reported. We did not identify any studies on melatonin. AUTHORS' CONCLUSIONS: Given the uncertain evidence on agomelatine and the absence of studies on melatonin, no conclusion about efficacy and safety of agomelatine and melatonin for prevention of SAD can currently be drawn. The decision for or against initiating preventive treatment of SAD and the treatment selected should consider patient preferences and reflect on the evidence base of all available treatment options.

User testing of an adaptation of fishbone diagrams to depict results of systematic reviews.

BACKGROUND: Summary of findings tables in systematic reviews are highly informative but require epidemiological training to be interpreted correctly. The usage of fishbone diagrams as graphical displays could offer researchers an effective approach to simplify content for readers with limited epidemiological training. In this paper we demonstrate how fishbone diagrams can be applied to systematic reviews and present the results of an initial user testing. METHODS: Findings from two systematic reviews were graphically depicted in the form of the fishbone diagram. To test the utility of fishbone diagrams compared with summary of findings tables, we developed and pilot-tested an online survey using Qualtrics. Respondents were randomized to the fishbone diagram or a summary of findings table presenting the same body of evidence. They answered questions in both open-ended and closed-answer formats; all responses were anonymous. Measures of interest focused on first and second impressions, the ability to find and interpret critical information, as well as user experience with both displays. We asked respondents about the perceived utility of fishbone diagrams compared to summary of findings tables. We analyzed quantitative data by conducting t-tests and comparing descriptive statistics. RESULTS: Based on real world systematic reviews, we provide two different fishbone diagrams to show how they might be used to display complex information in a clear and succinct manner. User testing on 77 students with basic epidemiological training revealed that participants preferred summary of findings tables over fishbone diagrams. Significantly more participants liked the summary of findings table than the fishbone diagram (71.8% vs. 44.8%; p < .01); significantly more participants found the fishbone diagram confusing (63.2% vs. 35.9%, p < .05) or indicated that it was difficult to find information (65.8% vs. 45%; p < .01). However, more than half of the participants in both groups were unable to find critical information and answer three respective questions correctly (52.6% in the fishbone group; 51.3% in the summary of findings group). CONCLUSIONS: Fishbone diagrams are compact visualizations that, theoretically, may prove useful for summarizing the findings of systematic reviews. Initial user testing, however, did not support the utility of such graphical displays.

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. PURPOSE: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. DATA SOURCES: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. STUDY SELECTION: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. DATA EXTRACTION: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. DATA SYNTHESIS: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. LIMITATION: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. CONCLUSION: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Second-generation antidepressants for preventing seasonal affective disorder in adults.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared an SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications and assigned risk of bias ratings based on the Cochrane 'Risk of bias' tool. We resolved disagreements by consensus or by consultation with a third party. Two review authors independently extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi(2) statistic and the Cochran Q. We used the I(2) statistic to estimate the magnitude of heterogeneity and examined potential sources of heterogeneity using sensitivity analysis or analysis of subgroups. We assessed publication bias by using funnel plots. However, given the small number of component studies in our meta-analyses, these tests have low sensitivity to detect publication bias. We rated the strength of the evidence using the system developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. MAIN RESULTS: We identified 2986 citations after de-duplication of search results and excluded 2895 records during title and abstract reviews. We assessed 91 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in patients with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; three RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 40% and 50%, NNTBs are 6 (95% CI 5 to 9) and 5 (95% CI 4 to 7), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, four of five patients will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment and might want to consider offering other potentially efficacious interventions, which might confer lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Light therapy for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery (e.g. visors, light boxes) and form of light (e.g. bright white light) vary. OBJECTIVES: To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trails (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non-randomised studies. We intended to include studies that compared any type of light therapy (e.g. bright white light, administered by visors or light boxes, infrared light, dawn stimulation) versus no treatment/placebo, second-generation antidepressants (SGAs), psychological therapies, melatonin, agomelatine, lifestyle changes, negative ion generators or another of the aforementioned light therapies. We also planned to include studies that looked at light therapy in combination with any comparator intervention and compared this with the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors independently abstracted data and assessed risk of bias of included studies. MAIN RESULTS: We identified 2986 citations after de-duplication of search results. We excluded 2895 records during title and abstract review. We assessed 91 full-text papers for inclusion in the review, but only one study providing data from 46 people met our eligibility criteria. The included randomised controlled trial (RCT) had methodological limitations. We rated it as having high risk of performance and detection bias because of lack of blinding, and as having high risk of attrition bias because study authors did not report reasons for dropouts and did not integrate data from dropouts into the analysis.The included RCT compared preventive use of bright white light (2500 lux via visors), infrared light (0.18 lux via visors) and no light treatment. Overall, both forms of preventive light therapy reduced the incidence of SAD numerically compared with no light therapy. In all, 43% (6/14) of participants in the bright light group developed SAD, as well as 33% (5/15) in the infrared light group and 67% (6/9) in the non-treatment group. Bright light therapy reduced the risk of SAD incidence by 36%; however, the 95% confidence interval (CI) was very broad and included both possible effect sizes in favour of bright light therapy and those in favour of no light therapy (risk ratio (RR) 0.64, 95% CI 0.30 to 1.38). Infrared light reduced the risk of SAD by 50% compared with no light therapy, but in this case also the CI was too broad to allow precise estimations of effect size (RR 0.50, 95% CI 0.21 to 1.17). Comparison of both forms of preventive light therapy versus each other yielded similar rates of incidence of depressive episodes in both groups (RR 1.29, 95% CI 0.50 to 3.28). The quality of evidence for all outcomes was very low. Reasons for downgrading evidence quality included high risk of bias of the included study, imprecision and other limitations, such as self rating of outcomes, lack of checking of compliance throughout the study duration and insufficient reporting of participant characteristics.Investigators provided no information on adverse events. We could find no studies that compared light therapy versus other interventions of interest such as SGA, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Evidence on light therapy as preventive treatment for patients with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.

Psychological therapies for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on psychological therapies as preventive interventions. OBJECTIVES: To assess the efficacy and safety of psychological therapies (in comparison with no treatment, other types of psychological therapy, second-generation antidepressants (SGAs), light therapy, melatonin or agomelatine or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We conducted a search of the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we planned to include randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared psychological therapy versus any other type of psychological therapy, placebo, light therapy, SGAs, melatonin, agomelatine or lifestyle changes. We also intended to compare psychological therapy in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors planned to independently extract data and assess risk of bias. We planned to pool data for meta-analysis when participant groups were similar and when studies assessed the same treatments versus the same comparator and provided similar definitions of outcome measures over a similar duration of treatment; however, we included no studies. MAIN RESULTS: We identified 2986 citations through electronic searches and reviews of reference lists after de-duplication of search results. We excluded 2895 records during title and abstract review and assessed 91 articles at full-text review for eligibility. We found no controlled studies on use of psychological therapy to prevent SAD and improve patient-centred outcomes in adults with a history of SAD. AUTHORS' CONCLUSIONS: Presently, there is no methodologically sound evidence available to indicate whether psychological therapy is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD. Randomised controlled trials are needed to compare different types of psychological therapies and to compare psychological therapies versus placebo, light therapy, SGAs, melatonin, agomelatine or lifestyle changes for prevention of new depressive episodes in patients with a history of winter-type SAD.

Melatonin and agomelatine for preventing seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD in the United States ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions. OBJECTIVES: To assess the efficacy and safety of agomelatine and melatonin (in comparison with each other, placebo, second-generation antidepressants, light therapy, psychological therapy or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We conducted a search of the Specialised Register of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. SELECTION CRITERIA: To examine efficacy, we planned to include randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second-generation antidepressant (SGA), light therapy, psychological therapies or lifestyle changes. We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions listed above versus the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors planned to independently extract data and assess risk of bias of included studies. We planned to pool data for meta-analysis when participant groups were similar and when studies assessed the same treatments by using the same comparator and presented similar definitions of outcome measures over a similar duration of treatment; however, we identified no studies for inclusion. MAIN RESULTS: We identified 2986 citations through electronic searches and reviews of reference lists after de-duplication of search results. We excluded 2895 records during title and abstract review and assessed 91 articles at full-text level for eligibility. We identified no controlled studies on use of melatonin and agomelatine to prevent SAD and to improve patient-centred outcomes among adults with a history of SAD. AUTHORS' CONCLUSIONS: No available methodologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD. Lack of evidence clearly shows the need for well-conducted, controlled studies on this topic. A well-conducted RCT of melatonin or agomelatine for prevention of SAD would assess the comparative benefits and risks of these interventions against others currently used to treat the disorder.

Meningococcal serogroup B vaccination series initiation in the United States: A real-world claims data analysis.

In the United States (US), meningococcal serogroup B (MenB) vaccination has been recommended for 16-23-year-olds (preferably 16-18 years) based on shared clinical decision-making since 2015. MenB vaccine coverage (≥1 dose) by age 17 years has been reported, but initiation at older ages and by insurance type is unknown. In this retrospective cohort study, MarketScan claims data were analyzed to assess MenB vaccine series initiation (i.e. receipt of a first dose) during 2017-2020 among US commercially insured and Medicaid-covered individuals aged 16-18 and 19-23 years. Kaplan-Meier curves were generated to estimate series initiation at various times from index (latest of 1/1/2017 or 16th/19th birthday, depending on the cohort). Multivariable analyses were conducted to identify factors associated with series initiation. Among 1,450,354 Commercial and 1,140,977 Medicaid 16-18-year-olds, MenB vaccine series initiation rates within 3 years of each person's first eligibility were estimated to be 33% and 20%, respectively; among 1,857,628 Commercial and 747,483 Medicaid 19-23-year-olds, 3% and 1%, respectively. Factors identified to be significantly associated with increased likelihood of initiating a MenB vaccine series included co-administration of meningococcal serogroups ACWY (MenACWY) vaccine, younger age, female sex, nonwhite race (Medicaid only), New England or Middle Atlantic location (Commercial only), urban residence, and previous influenza vaccination. MenB vaccine series initiation among the studied US adolescents and young adults was low. There is a need for continued efforts to better understand barriers to the uptake of vaccines that are recommended based on shared clinical decision-making.

Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review.

BACKGROUND: Patients with major depressive disorder (MDD) often suffer from accompanying symptoms that influence the choice of pharmacotherapy with second-generation antidepressants (SGAs). We conducted a systematic review to determine the comparative effectiveness of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, venlafaxine, bupropion, mirtazapine, nefazodone, and trazodone, for accompanying anxiety, insomnia, and pain in patients with MDD. METHODS: We conducted searches in multiple databases including MEDLINE®, Embase, the Cochrane Library, International Pharmaceutical Abstracts, and PsycINFO, from 1980 through August 2011 and reviewed reference lists of pertinent articles. We dually reviewed abstracts, full-text articles, and abstracted data. We included randomized, head-to-head trials of SGAs of at least 6 weeks' duration. We grouped SGAs into three classes for the analysis: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, and others. We graded the strength of the evidence as high, moderate, low, or very low based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (GRADE) approach. RESULTS: We located 19 head-to-head trials in total: 11 on anxiety, six on insomnia, and four on pain. For the majority of comparisons, the strength of the evidence was moderate or low: evidence is weakened by inconsistency and imprecision. For treating anxiety, insomnia, and pain moderate evidence suggests that the SSRIs do not differ. CONCLUSIONS: Evidence guiding the selection of an SGA based on accompanying symptoms of depression is limited. Very few trials were designed and adequately powered to answer questions about accompanying symptoms; analyses were generally of subgroups in larger MDD trials.

Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.

BACKGROUND: Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory. PURPOSE: To compare the benefits and harms of second-generation antidepressants for treating MDD in adults. DATA SOURCES: English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature. STUDY SELECTION: 2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm. DATA EXTRACTION: Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings. DATA SYNTHESIS: Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life. LIMITATIONS: Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited. CONCLUSION: Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

A Real-world Claims Data Analysis of Meningococcal Serogroup B Vaccine Series Completion and Potential Missed Opportunities in the United States.

BACKGROUND: In the United States, meningococcal serogroup B (MenB) vaccination is recommended for 16-23-year-olds based on shared clinical decision-making. We estimated series completion among individuals initiating MenB vaccination for the 2 available vaccines: MenB 4-component (MenB-4C, doses at 0 and ≥1 month) and MenB factor H binding protein (MenB-FHbp, doses at 0 and 6 months). METHODS: This retrospective health insurance claims data analysis included 16-23-year-olds who initiated MenB vaccination (index date) during January 2017 to November 2018 (MarketScan Commercial Claims and Encounters Database) or January 2017 to September 2018 (MarketScan Multi-State Medicaid Database) and had continuous enrollment for ≥6 months before and ≥15 months after index. The main outcome was MenB vaccine series completion within 15 months. Among noncompleters, preventive care/well-child and vaccine administrative office visits were identified as potential missed opportunities for series completion. Robust Poisson regression models identified independent predictors of series completion. RESULTS: In the Commercial (n = 156,080) and Medicaid (n = 57,082) populations, series completion was 56.7% and 44.7%, respectively, and was higher among those who initiated MenB-4C versus MenB-FHbp (61.1% versus 49.8% and 47.8% versus 33.9%, respectively; both P < 0.001). Among noncompleters, 40.2% and 34.7% of the Commercial and Medicaid populations, respectively, had ≥1 missed opportunity for series completion. Receipt of MenB-4C and younger age were independently associated with a higher probability of series completion. CONCLUSIONS: Series completion rates were suboptimal but were higher among those who initiated MenB-4C. To maximize the benefits of MenB vaccination, interventions to improve completion and reduce missed opportunities should be implemented.

Systematic review of context-aware digital behavior change interventions to improve health.

Health risk behaviors are leading contributors to morbidity, premature mortality associated with chronic diseases, and escalating health costs. However, traditional interventions to change health behaviors often have modest effects, and limited applicability and scale. To better support health improvement goals across the care continuum, new approaches incorporating various smart technologies are being utilized to create more individualized digital behavior change interventions (DBCIs). The purpose of this study is to identify context-aware DBCIs that provide individualized interventions to improve health. A systematic review of published literature (2013-2020) was conducted from multiple databases and manual searches. All included DBCIs were context-aware, automated digital health technologies, whereby user input, activity, or location influenced the intervention. Included studies addressed explicit health behaviors and reported data of behavior change outcomes. Data extracted from studies included study design, type of intervention, including its functions and technologies used, behavior change techniques, and target health behavior and outcomes data. Thirty-three articles were included, comprising mobile health (mHealth) applications, Internet of Things wearables/sensors, and internet-based web applications. The most frequently adopted behavior change techniques were in the groupings of feedback and monitoring, shaping knowledge, associations, and goals and planning. Technologies used to apply these in a context-aware, automated fashion included analytic and artificial intelligence (e.g., machine learning and symbolic reasoning) methods requiring various degrees of access to data. Studies demonstrated improvements in physical activity, dietary behaviors, medication adherence, and sun protection practices. Context-aware DBCIs effectively supported behavior change to improve users' health behaviors.

Outcomes and costs of community health worker interventions: a systematic review.

OBJECTIVES: We conducted a systematic review on outcomes and costs of community health worker (CHW) interventions. CHWs are increasingly expected to improve health outcomes cost-effectively for the underserved. RESEARCH DESIGN: We searched Medline, Cochrane Collaboration resources, and the Cumulative Index to Nursing and Allied Health Literature for studies conducted in the United States and published in English from 1980 through November 2008. We dually reviewed abstracts, full-text articles, data abstractions, quality ratings, and strength of evidence grades and resolved disagreements by consensus. RESULTS: We included 53 studies on outcomes of CHW interventions and 6 on cost or cost-effectiveness. For outcomes, limited evidence (5 studies) suggests that CHW interventions can improve participant knowledge compared with alternative approaches or no intervention. We found mixed evidence for participant behavior change (22 studies) and health outcomes (27 studies). Some studies suggested that CHW interventions can result in greater improvements in participant behavior and health outcomes compared with various alternatives, but other studies suggested that CHW interventions provide no statistically different benefits than alternatives. We found low or moderate strength of evidence suggesting that CHWs can increase appropriate health care utilization for some interventions (30 studies). Six studies with economic information yielded insufficient data to evaluate the cost-effectiveness of CHW interventions relative to other interventions. CONCLUSIONS: CHWs can improve outcomes for underserved populations for some health conditions. The effectiveness of CHWs in many health care areas requires further research that addresses the methodologic limitations of prior studies and that contributes to translating research into practice.

Semi-automating the manual literature search for systematic reviews increases efficiency.

BACKGROUND: To minimise retrieval bias, manual literature searches are a key part of the search process of any systematic review. Considering the need to have accurate information, valid results of the manual literature search are essential to ensure scientific standards; likewise efficient approaches that minimise the amount of personnel time required to conduct a manual literature search are of great interest. OBJECTIVE: The objective of this project was to determine the validity and efficiency of a new manual search method that utilises the scopus database. METHODS: We used the traditional manual search approach as the gold standard to determine the validity and efficiency of the proposed scopus method. Outcome measures included completeness of article detection and personnel time involved. Using both methods independently, we compared the results based on accuracy of the results, validity and time spent conducting the search, efficiency. RESULTS: Regarding accuracy, the scopus method identified the same studies as the traditional approach indicating its validity. In terms of efficiency, using scopus led to a time saving of 62.5% compared with the traditional approach (3 h versus 8 h). CONCLUSIONS: The scopus method can significantly improve the efficiency of manual searches and thus of systematic reviews.

Inadequate reporting of trials compromises the applicability of systematic reviews.

BACKGROUND: Uncertainty about the applicability of controlled trial findings is an increasing concern for clinicians and policy decision makers. This study aimed to determine whether information reported in studies included in systematic reviews was adequate enough to assess their applicability. METHODS: We used the databases of four recently conducted systematic reviews on the comparative efficacy and safety of second-generation antidepressants, inhaled corticosteroids, Alzheimer's drugs, and targeted immune modulators. We developed and pilot-tested a questionnaire to assess the adequacy of reporting with respect to seven previously validated criteria of study design that distinguish explanatory from pragmatic studies. For each of the 137 included studies, two reviewers independently assessed the adequacy of reporting. RESULTS: Overall, only 12 percent of the included studies provided sufficient information to reliably distinguish explanatory from pragmatic studies. The areas with the greatest lack of reporting were the setting of the study, methods of adverse event assessment, and sample size considerations to determine a minimally important difference from a patient perspective. CONCLUSIONS: Substantial shortcomings in reporting exist in aspects of study design important to determine whether a study is applicable to specific populations of interest.