[Evidence-b(i)ased psychiatry: research into the evidence for effectiveness and safety of antidepressants in depression and anxiety disorders]. / Evidence-b(i)ased psychiatrie: onderzoek naar bewijs voor effectiviteit en veiligheid van antidepressiva bij depressie en angststoornissen.

BACKGROUND: Antidepressants remain controversial, partly due to allegations that disappointing results were buried and because of their modest average efficacy.
AIM: To investigate bias in the antidepressant literature and the possibilities for predicting which patients with depression or anxiety do receive significant benefits from antidepressants.
METHOD: We investigated bias by comparing information from the US Food and Drug Administration with the published literature. To predict response, we used patient data from randomized trials.
RESULTS: Of all studies on depression or anxiety, 50% and 72% were positive, compared to 95% and 96% of all published studies. Safety outcomes were poorly reported in published articles and unpublished studies were often 'bundled' into pooled-trials publications with positive conclusions. We found an association between severity and antidepressant efficacy for some, but not all, anxiety disorders; previous research has found inconsistent evidence for this association for depression. Furthermore, patients with depression that showed early improvement were more likely to attain a good response, irrespective of which symptoms improved.
CONCLUSION: These results demonstrate the severe impact of bias on the antidepressant literature. Severity and early improvement predicted a good response, but more information is needed to improve predictions. The increased accessibility of individual patient data will hopefully soon enable further progress in this area.

Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

Cognitive/affective and somatic/affective symptoms of depression in patients with heart disease and their association with cardiovascular prognosis: a meta-analysis.

BACKGROUND: Several prospective longitudinal studies have suggested that somatic/affective depressive symptoms, but not cognitive/affective depressive symptoms, are related to prognosis in patients with heart disease, but findings have been inconsistent. The aim of this study was to investigate the association of cognitive/affective and somatic/affective symptoms of depression with cardiovascular prognosis in patients with heart disease using a meta-analytic perspective. METHOD: A systematic search was performed in PubMed, EMBASE and PsycInfo. Thirteen prospective studies on symptom dimensions of depression and cardiovascular prognosis fulfilled the inclusion criteria, providing data on a total of 11,128 subjects. The risk estimates for each dimension of depressive symptoms, demographic and methodological variables were extracted from the included articles. RESULTS: In least-adjusted analyses, both the somatic/affective [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.19-1.41, p < 0.001] and cognitive/affective (HR 1.07, 95% CI 1.00-1.15, p = 0.05) dimensions of depressive symptoms were associated with cardiovascular prognosis. In fully adjusted analyses, somatic/affective symptoms were significantly associated with adverse prognosis (HR 1.19, 95% CI 1.10-1.29, p < 0.001) but cognitive/affective symptoms were not (HR 1.04, 95% CI 0.97-1.12, p = 0.25). An increase of one standard deviation (±1 s.d.) in the scores of the somatic/affective dimension was associated with a 32% increased risk of adverse outcomes (HR 1.32, 95% CI 1.17-1.48, p < 0.001). CONCLUSIONS: Somatic/affective depressive symptoms were more strongly and consistently associated with mortality and cardiovascular events in patients with heart disease compared with cognitive/affective symptoms. Future research should focus on the mechanisms by which somatic/affective depressive symptoms may affect cardiovascular prognosis.

Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries.

AIMS: Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys. METHODS: The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women. RESULTS: Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2-110.8, interquartile range = 6.0-19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1-2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs. CONCLUSIONS: Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

Fear and distress disorders as predictors of heart disease: A temporal perspective.

OBJECTIVE: Few studies have been able to contrast associations of anxiety and depression with heart disease. These disorders can be grouped in fear and distress disorders. Aim of this study was to study the association between fear and distress disorders with subsequent heart disease, taking into account the temporal order of disorders. METHODS: Twenty household surveys were conducted in 18 countries (n=53791; person years=2,212,430). The Composite International Diagnostic Interview assessed lifetime prevalence and age at onset of disorders, and respondents were categorized into categories based on the presence and timing of fear and distress disorders. Heart disease was indicated by self-report of physician-diagnosed heart disease or self-report of heart attack, together with year of onset. Survival analyses estimated associations between disorder categories and heart disease. RESULTS: Most respondents with fear or distress disorders had either pure distress or pure fear (8.5% and 7.7% of total sample), while fear preceded distress in the large majority of respondents with comorbid fear and distress (3.8% of total sample). Compared to the "no fear or distress disorder" category, respondents with pure fear disorder had the highest odds of subsequent heart disease (OR:1.8; 95%CI:1.5-2.2; p<0.001) and compared to respondents with pure distress disorder, these respondents were at a significantly increased risk of heart disease (OR:1.3; 95%CI:1.0-1.6; p=0.020). CONCLUSION: This novel analytic approach indicates that the risk of subsequent self-reported heart disease associated with pure fear disorder is significantly larger than the risk associated with distress disorder. These results should be confirmed in prospective studies using objective measures of heart disease.

A systematic review and meta-analysis of the percentage of revised diagnoses in functional somatic symptoms.

BACKGROUND: Functional somatic symptoms (FSS) are bodily complaints of unclear etiology, which are (currently) not fully explained by well-recognized somatic pathology. Doctors are often hesitant to diagnose FSS, due to the risk to miss a somatic disease. The purpose of this study is to review available literature on the percentage of patients diagnosed with FSS reported to have an underlying somatic disease that explains their symptoms previously labeled as FSS. METHODS: We performed a systematic search of Medline, Embase and PsycINFO databases and reference lists of selected articles. We included studies published between January 1980 and July 2014 without language restrictions. Studies that measured the percentage of underlying somatic diseases after a diagnostic evaluation or naturalistic follow-up period in adult patients initially diagnosed with FSS were included. As primary outcome measure the weighted percentage of revised diagnoses was calculated using meta-analyses. RESULTS: Six diagnostic evaluation studies (total N=1804 patients) and 16 follow-up studies (total N=2440 patients) were included. The percentage of revised diagnosis in patients initially diagnosed with FSS was 8.8% (95% CI 1.0 to 22.2, p=0.007) in diagnostic evaluation studies and 0.5% (95% CI 0.01 to 1.5, p=0.03) in follow-up studies. Partially or possibly related diagnoses were rarely found. No specific somatic diagnosis seemed to be missed systematically. CONCLUSIONS: The percentage of underlying somatic diseases in patients previously diagnosed with FSS is relatively small but unneglectable.

Physical activity and onset of depression in adolescents: a prospective study in the general population cohort TRAILS.

Although it has often been suggested that physical activity and depression are intertwined, only few studies have investigated whether specific aspects of physical activity predict the incidence of major depression in adolescents from the general population. Therefore the aim of this study was to investigate the effects of nature, frequency, duration and intensity of physical activity during early adolescence on the onset of a major depressive episode in early adulthood. In a population sample of adolescents (N = 1396), various aspects of physical activity were assessed at early adolescence (mean age 13.02, SD = 0.61). Major depressive episode onset was assessed using the Composite International Diagnostic Interview. A Cox regression model was performed to investigate whether physical activity characteristics and their interactions with gender predicted a major depressive episode onset up until mean age 18.5 (SD = 0.61). The individual characteristics of physical activity (nature, frequency, duration and intensity) or their interactions with gender did not predict a major depressive episode onset (p values >0.05). So far, there is no prospective evidence that physical activity protects against the development of adolescent depressive episodes in either boys or girls.