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Meta-analysis. A review of its place in therapeutic decision making.

The potential value of meta-analysis has captured the imagination of many investigators. Epidemiologists have, appropriately, greeted its broad application with considerable caution, yet practical matters, such as the need to consolidate and extract information from available data, have forced a more accepting approach. Meta-analysis has been employed in many clinical settings to evaluate efficacy and safety of a variety of therapeutic interventions. It is likely that it will continue to have a role in extrapolating data from clinical trials for use in the clinic.

Decision Support Techniques↗

Psychological impact of genetic counseling for familial cancer: a systematic review and meta-analysis.

BACKGROUND: Identification of a genetic basis underlying certain types of cancer has led to an increase in demand for genetic counseling about individual risks of the disease. We conducted a systematic review of the literature to determine the quality and strength of evidence relating to psychological outcomes of genetic counseling for familial cancer. METHODS: Six electronic databases were searched to identify controlled trials and prospective studies that examined the effect of genetic counseling on risk perception, knowledge, anxiety, cancer-specific worry, depression, and cancer surveillance. Twenty-one studies from 25 papers met inclusion criteria, including five controlled trials and 16 prospective studies. Analysis of each outcome was stratified by short-term (</=1 month) and long-term (>/=3 months) follow-up. Trial evidence was assessed with standardized differences of the means at follow-up between intervention and comparison groups, and these data were pooled by use of random-effects meta-analysis. RESULTS: Meta-analysis of controlled trials showed that genetic counseling improved knowledge of cancer genetics (pooled short-term difference=0.70 U, 95% confidence interval (CI)=0.15 to 1.26 U) but did not alter the level of perceived risk (pooled short-term difference=-0.10 U, 95% CI=-0.23-0.04 U). Prospective studies reported improvements in the accuracy of perceived risk. No effect was observed in controlled trials on general anxiety (pooled long-term effect=0.05 U, 95% CI=-0.21-0.31 U) or cancer-specific worry (pooled long-term difference=-0.14 U, 95% CI=-0.35-0.06 U), although several prospective studies demonstrated short-term reductions in these outcomes. Few studies examined cancer surveillance behaviors, and no studies attempted to measure informed choice. CONCLUSIONS: Genetic counseling for familial cancer is associated with improvement in knowledge but does not have an adverse effect on affective outcomes. We urge further investigation of these findings through well-designed, well-reported, randomized controlled trials with suitable comparison groups and additional outcome measures [J Natl Cancer Inst 2004; 96:122-33].

Attitude to Health↗

A meta-analysis of trials comparing Cypher and Taxus stents in patients with obstructive coronary artery disease.

AIMS: Drug-eluting stents have been shown to be superior to bare metal stents in reducing restenosis rates. Recently head-to-head trials comparing sirolimus-eluting stents and paclitaxel-eluting stents have been reported. An early combined analysis of these comparative trials is needed. The present meta-analysis was carried out to compare the effects of sirolimus-eluting stents with paclitaxel-eluting stents on the restenosis rate, major adverse cardiac events and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Electronic (Medline, Cochrane and Embase) and manual search (Index Medicus and cross references of retrieved articles) were carried out for all the relevant articles up till March 2005. Only randomized trials with adequate data for calculation of odds ratio for restenosis rates and major adverse cardiac events using the method of DerSimonian & Laird and standardized mean difference for late loss of arterial lumen diameter were included. RESULTS: Four studies were found to be eligible for inclusion in the meta-analysis. Restenosis rate and late loss of arterial lumen diameter were significantly reduced by sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.598, 95% CI 0.400, 0.893, pooled mean difference -0.414, 95% CI -0.492, 0.336, respectively). The incidence of major adverse cardiac events was less with sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.727, 95% CI 0.518-1.018) but the results were not statistically significant. CONCLUSIONS: Sirolimus-eluting stents are superior to paclitaxel-eluting stents in decreasing restenosis rate and late loss of arterial lumen diameter. However, no statistically significant difference in major adverse cardiac events was noted between the two stents.

Coronary Stenosis↗

Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer.

STUDY OBJECTIVE: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer. DESIGN: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. SETTING: Populations in Europe and North America. PARTICIPANTS: Those included in six case-control studies (6084 incident bladder cancer cases, 10,816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. MAIN RESULTS: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. CONCLUSIONS: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods.

Chlorine↗

[Gibbs-Sampler approach for meta-analysis of multiple clinical trials using generalized linear model with random-effects].

OBJECTIVE: To investigate the use of the Gibbs-Sampler method in evaluating the relationship between clinic events and health risks in a meta-analysis of multiple clinical trials. METHODS: By using a generalized linear model with random-effects, Gibbs-Sampler technique was used in a meta-analysis of multiple clinical trials of angiotensin converting enzyme (ACE) inhibitors in patients with myocardial infarction (MI). RESULTS: When heterogeneity across different trials can not be ignored, compared with the classic method, the odds ratio of relative reinfarction risk estimated by the Gibbs-Sampler method would have less variation. The gain in the reduction of variation in estimate of the overall odds ratio was 9.52%. CONCLUSION: Implementation of the Gibbs-Sampler technique in meta-analysis of multiple clinical trials has the potential of reducing the inaccuracy caused by heterogeneity across trials.

Angiotensin-Converting Enzyme Inhibitors↗

Individual patient-versus literature-based meta-analysis of survival data: time to event and event rate at a particular time can make a difference, an example based on head and neck cancer.

The objective of this study is to compare the results of an individual patient-based and a literature-based meta-analysis in chemotherapy in head and neck cancer and to identify the sources of difference. For all head and neck cancer randomized controlled clinical trials comparing chemotherapy and loco-regional treatment with loco-regional treatment alone, both the literature data and the individual patient data are retrieved and meta-analyses performed and compared. Only survival data are used as outcome, although both time to death and mortality at specific time points are considered in different analyses. There are substantial differences between the individual patient-based and the literature-based meta-analyses. The most important reason for the differing results is that the individual patient-based meta-analysis is based on a time to event analysis, whereas the literature-based meta-analysis is based on mortality at a specific time point. Mortality can change substantially with follow-up time. The absolute survival differences in the case study, for instance, increase from 2.6% at 2 years to 5.6% at 5 years.

Antineoplastic Agents↗

Drug treatment of functional dyspepsia. A meta-analysis of randomized controlled clinical trials.

The results of therapeutic trials in functional dyspepsia (FD), a frequently encountered condition, are contradictory. Our aim, then, was to produce a pooled estimate, or meta-analysis, of a series of short-term randomized placebo-controlled clinical trials on the pharmacological treatment of FD with antisecretory and gastrokinetic drugs. We retrieved trials for analysis purposes by consulting computerized data bases and by scanning published reviews, Current Contents, and references cited in the individual studies. We also requested bibliographical updates from the medical departments of the manufacturers of the drugs used in the various trials. Of 74 trials retrieved by these means, 23 proved eligible for meta-analysis on the basis of six selection criteria defined a priori. Results were expressed in terms of "therapeutic success" (TS), which includes "symptom-free patients," patients with "significant improvement in symptoms," "excellent results," and so on. The differences in TS rates between the various drugs and placebo were calculated in each trial as the algebraic difference together with the respective 95% confidence interval (95% C.I.); the pooling of results of all eligible trials was done using Cochran's weighted method. With antisecretory drugs, the mean difference in TS rates versus placebo was +20% (95% C.I.: 14-24%). The therapeutic gain for the respective antisecretory agents was 25% (95% C.I.: 14-36%) in the case of pirenzepine and 18% (95% C.I.: 12-24%) in the case of H2 antagonists. Meta-analysis of trials with gastrokinetic drugs also showed superior efficacy of these agents compared with placebo, with a mean difference in TS rates of +46% (95% C.I.: 40-52%).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Psychological impact of genetic counseling for familial cancer: a systematic review and meta-analysis.

BACKGROUND: Identification of a genetic basis underlying certain types of cancer has led to an increase in demand for genetic counseling about individual risks of the disease. We conducted a systematic review of the literature to determine the quality and strength of evidence relating to psychological outcomes of genetic counseling for familial cancer. METHODS: Six electronic databases were searched to identify controlled trials and prospective studies that examined the effect of genetic counseling on risk perception, knowledge, anxiety, cancer-specific worry, depression, and cancer surveillance. Twenty-one studies from 25 papers met inclusion criteria, including five controlled trials and 16 prospective studies. Analysis of each outcome was stratified by short-term (< or =1 month) and long-term (> or = 3 months) follow-up. Trial evidence was assessed with standardized differences of the means at follow-up between intervention and comparison groups, and these data were pooled by use of random-effects meta-analysis. RESULTS: Meta-analysis of controlled trials showed that genetic counseling improved knowledge of cancer genetics (pooled short-term difference = 0.70 U, 95% confidence interval [CI] = 0.15 to 1.26 U) but did not alter the level of perceived risk (pooled short-term difference = -0.10 U, 95% CI = -0.23 to 0.04 U). Prospective studies reported improvements in the accuracy of perceived risk. No effect was observed in controlled trials on general anxiety (pooled long-term effect = 0.05 U, 95% CI = -0.21 to 0.31 U) or cancer-specific worry (pooled long-term difference = -0.14 U, 95% CI = -0.35 to 0.06 U), although several prospective studies demonstrated short-term reductions in these outcomes. Few studies examined cancer surveillance behaviors, and no studies attempted to measure informed choice. CONCLUSIONS: Genetic counseling for familial cancer is associated with improvement in knowledge but does not have an adverse effect on affective outcomes. We urge further investigation of these findings through well-designed, well-reported, randomized controlled trials with suitable comparison groups and additional outcome measures.

Affect↗

Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.

BACKGROUND: Laparoscopic surgery presents a large number of advantages over laparotomy. The goal of this work was to check whether these benefits outweigh any greater risk of complications. METHODS: The study design was a meta-analysis of published data from prospective randomized clinical trials (RCT). For the period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial Registers and asked the investigators for further details. Meta-analysis was carried out with the Cochrane review manager software RevMan 4.1. RESULTS: A total of 27 prospective RCT including 3611 women (1809 treated by operative laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis. The overall risk of complications was significantly lower for patients operated by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI) 0.50-0.70]. There was no statistically significant difference concerning the risk of major complications with respect to the approach used (RR 1.0; 95% CI 0.60-1.65). The risk of minor complications was significantly lower for patients operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the risks of readmission, second procedure and blood transfusion, there was no difference between the two groups. Identical results were found when we performed a sensitivity analysis including or excluding studies according to the methodological score. Subgroup analysis according to how serious the surgery was (minor, major, advanced) showed a significant increase in the risk of transfusion for advanced procedures performed by laparotomy. CONCLUSIONS: Laparoscopic surgery is not inherently dangerous for patients presenting benign gynaecological pathologies. The potential risk of complications should no longer be advanced as an argument against using laparoscopic surgery rather than laparotomy for an operation when the indication allows the choice.

Female↗

Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis.

OBJECTIVE: To examine the association between coronary heart disease and serum markers of chronic Chlamydia pneumoniae infection. DESIGN: "Nested" case-control analysis in a prospective cohort study and an updated meta-analysis of previous relevant studies. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: Of the 5661 men aged 40-59 who provided blood samples during 1978-80, 496 men who died from coronary heart disease or had non-fatal myocardial infarction and 989 men who had not developed coronary heart disease by 1996 were included. MAIN OUTCOME MEASURES: IgG serum antibodies to C pneumoniae in baseline samples; details of fatal and non-fatal coronary heart disease from medical records and death certificates. RESULTS: 200 (40%) of the 496 men with coronary heart disease were in the top third of C pneumoniae titres compared with 329 (33%) of the 989 controls. The corresponding odds ratio for coronary heart disease was 1.66 (95% confidence interval 1.25 to 2.21), which fell to 1.22 (0.82 to 1.82) after adjustment for smoking and indicators of socioeconomic status. No strong associations were observed between C pneumoniae IgG titres and blood lipid concentrations, blood pressure, or plasma homocysteine concentration. In aggregate, the present study and 14 other prospective studies of C pneumoniae IgG titres included 3169 cases, yielding a combined odds ratio of 1. 15 (0.97 to 1.36), with no significant heterogeneity among the separate studies (chi(2)=10.5, df=14; P>0.1). CONCLUSION: This study, together with a meta-analysis of previous prospective studies, reliably excludes the existence of any strong association between C pneumoniae IgG titres and incident coronary heart disease. Further studies are required, however, to confirm or refute any modest association that may exist, particularly at younger ages.

Adult↗

A meta-analysis of the effects of exercise and/or dietary restriction on resting metabolic rate.

A meta-analysis was used to examine the independent and interactive effects of dietary restriction, endurance exercise training and gender on resting metabolic rate (RMR). Sixty different group means (covering approximately 650 subjects) were identified from the scientific literature and subjected to meta-analysis techniques. Collectively (i.e., all groups combined), body weight loss was greater (P < 0.05) for men (approximately 18 kg) than for women (approximately 12 kg). There were no statistically significant exercise training or gender effects on RMR during weight loss. Collectively (i.e., all groups combined), dietary restriction resulted in a -0.59 kJ.min-1 (approximately -12%) decrease in RMR (P < 0.05). When normalized to body weight, RMR was reduced by less than 2% (P < 0.05). These data suggest that exercise training does not differentially affect RMR during diet-induced weight loss. In addition, decreases in resting metabolism appear to be proportional to the loss of the metabolically active tissue.

Diet, Reducing↗

Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas--experience and meta-analysis.

BACKGROUND: Recommendations on the use of I-123 metaiodobenzylguanidine (MIBG) scintigraphy in localising phaeochromocytomas vary. The accuracy of I-123 MIBG scintigraphy was determined by evaluating our own I-123 MIBG scans and performing a meta-analysis. MATERIALS AND METHODS: Between January 1992 and May 2002, the I-123 MIBG scans of consecutive patients suspected of a phaeochromocytoma were re-evaluated. For the meta-analysis, studies with more than 5 I-123 MIBG scans were selected. RESULTS: Thirty patients were evaluated. The sensitivity in our own population was 92% and the specificity was 100%. Twelve articles were selected for our meta-analysis. The overall sensitivity and specificity were 96% and 100%, respectively. The sensitivity and specificity for tumours in the adrenal gland was 98% for both. For tumours located outside the adrenal gland, the sensitivity was 98% and the sensitivity for malignancies was 79%. CONCLUSION: 1-123 MIBG scintigraphy has an excellent sensitivity and specificity in localising phaeochromocytomas, except for malignant tumours. 1-123 MIBG scintigraphy is superior in localising tumours outside the adrenal gland.

3-Iodobenzylguanidine↗

Helicobacter pylori infection and colorectal cancer risk: a meta-analysis.

BACKGROUND: Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta-analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies. MATERIALS AND METHODS: An extensive literature search and cross-referencing were performed to identify all published studies. Summary estimates were obtained using random-effects models. The presence of possible publication bias was assessed using different statistical approaches. RESULTS: In a meta-analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1-1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%). CONCLUSIONS: The results of our meta-analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.

Adult↗

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I&#xb2; = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans↗

Epidemiological association between cigarette smoking and primary open-angle glaucoma: a meta-analysis.

OBJECTIVE: The role of cigarette smoking as a risk factor for primary open-angle glaucoma (POAG) remains controversial. The aim of this study was to examine this association by conducting a detailed meta-analysis of studies published in peer-reviewed literature on the subject. METHODS: A comprehensive search for articles published up 31 December 2002 was performed, reviews of each study were conducted, and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. RESULTS: Our analysis was based on seven reports. We found no evidence of publication bias or heterogeneity among the studies. The summary odds ratios from a fixed-effects model were 1.37 (95% CI: 1.00-1.87) for current smokers and 1.03 (95% CI: 0.77-1.38) for past smokers. CONCLUSIONS: Our meta-analysis results suggest that current smokers are at significantly increased risk of developing POAG. Efforts should be directed towards augmenting the campaign against smoking by adding the increased risk of POAG to the better-known arguments against smoking.

Glaucoma, Open-Angle↗

Predicting treatment time with the Lidcombe Program: replication and meta-analysis.

BACKGROUND: The benefits of treating stuttering close to onset have become obvious in recent years, and the Lidcombe Program has emerged as an effective and safe treatment method for children in their preschool years. The benefits of implementing the programme with young children, however, need to be weighed against the knowledge that many children recover from stuttering without treatment. In light of this, speech-language therapists need to know how long treatment is likely to take and whether treatment time can be predicted. In particular, they need to know if adopting a 'watchful waiting' approach--to see if natural recovery occurs--jeopardizes responsiveness to treatment. A recent Australian study of 250 preschool-age children found that stuttering rate was the only significant predictor of treatment time with the Lidcombe Program. In other words, children whose stuttering was more severe took longer to pass through the programme. There were other trends in the data but they did not reach significance. AIMS: The present study, conducted independently in the UK, was designed to replicate the Australian study. Direct replication enabled pooling of the data from the two studies in a meta-analysis. METHODS & PROCEDURES: The study included 66 children who began treatment before 6 years of age. They were treated with the Lidcombe Program at a specialist stuttering clinic in Norwich. Logistic regression analyses were conducted on the data. The data from both the British and Australian cohorts were pooled in a meta-analysis. OUTCOMES & RESULTS: Results indicated that Stage 1 of the Lidcombe Program was completed in a median of 11 clinic visits, which is in line with the findings of the Australian study. Stuttering rate at first clinic visit was again found to be a significant predictor of treatment time. The remaining data trends were similar to those in the Australian data. In the meta-analysis, stuttering rate was once more found to be a predictor of treatment time. Of particular interest, however, was that the increased power provided by the meta-analysis identified an additional predictor, namely onset-to-treatment interval. Contrary to what is known about the responsiveness of children to the Starkweather and Gottwald treatment, and contrary to what might be expected given what we know about natural recovery, children who had been stuttering for more than 12 months took less time to progress through the programme than children who had been stuttering for less than 12 months. CONCLUSIONS: These findings indicate that delaying intervention with the Lidcombe Program for 1 year after onset, within the preschool years, is unlikely to jeopardize responsiveness to treatment. The clinical implications of these findings are discussed.

Age Factors↗

Effects of fish oil supplementation on kidney transplantation: a systematic review and meta-analysis of randomized, controlled trials.

The objective of this study was to assess the effects of omega-3 fatty acid supplementation on various kidney transplant-related outcomes. A systematic review and meta-analysis was performed of published randomized, controlled trials (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No consistent benefits were observed for any outcome with the exception of a modest benefit on triglycerides. A meta-analysis of rejection episodes found no significant benefit on either early (<6 mo posttransplantation) or late episodes. The overall relative risk of having at least one rejection episode in those who received fish oil was 0.91 (95% confidence interval 0.74 to 1.10) in four studies with a follow-up of 1 yr. A meta-analysis of eight RCT of graft survival found no significant benefit (relative risk 1.00, 95% confidence interval 0.96 to 1.05). The available data (mostly derived from older studies with important methodologic limitations) do not demonstrate a consistent, clinically important benefit of fish oil in kidney transplantation.

Clinical Trials as Topic↗

Relative efficacy of psychotherapy and combined therapy in the treatment of depression: a meta-analysis.

BACKGROUND: Reviews of the relative efficacy of psychotherapy and combined therapy (psychotherapy with pharmacotherapy) for depression have yielded contradicting conclusions. This may be explained by the clinical heterogeneity of the studies reviewed. AIMS: To conduct a meta-analysis with an acceptable level of homogeneity in order to investigate the relative efficacy of psychotherapy and combined therapy in the acute treatment of depression. METHOD: A systematic search was performed for RCTs published between 1980 and 2005 comparing psychotherapy and combined therapy in adult psychiatric outpatients with non-psychotic unipolar major depressive disorder. The studies were classified according to the chronicity and severity of the depression. Data were pooled by means of meta-analysis and statistical tests were conducted to measure heterogeneity. RESULTS: The meta-analysis included seven studies looking at a total of 903 patients. None of the heterogeneity tests established significance. This indicates a lack of evidence for the heterogeneity of the results. The dropout rates did not differ significantly between the two treatment modalities (25% in combined therapy and 24% in psychotherapy, p=0.77). At treatment termination, the intention-to-treat remission rate for combined therapy (46%) was better than for psychotherapy (34%) (p=0.0007); Relative Risk 1.32 (95% CI: 1.12-1.56), Odds Ratio 1.59 (95% CI: 1.22-2.09). In moderate depression, the difference between the remission rate for combined therapy and psychotherapy was statistically significant (47% compared to 34% respectively, p=0.001). This was not the case in mild major depression (42% compared to 37% respectively, p=0.29). The difference was also statistically significant in chronic major depression (48% compared to 32%, p<0.001), but not in non-chronic major depression (43% compared to 37%, p=0.22). On a more specific level, no differences were found in the remission rates for the treatment modalities in mild or moderate non-chronic depression. Combined therapy led to significantly better results than psychotherapy in moderate chronic depression only (48% compared to 32%, p<0.001). CONCLUSIONS: In the acute treatment of adult psychiatric outpatients with major depressive disorder, patient compliance with combined therapy matches compliance with psychotherapy alone. Combined therapy is more efficacious than psychotherapy alone. However, these results depend on severity and chronicity. Combined therapy outperformed psychotherapy in moderate chronic depression only. No differences were found in mild and moderate non-chronic depression. No data were found for mild chronic depression and for severe depression.

Chronic Disease↗