Henk Jan Conradi

Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research

OBJECTIVE A meta-analysis of over 25 years of research into the relationship between post-myocardial infarction (MI) depression and cardiac prognosis was conducted to investigate changes in this association over time and to investigate subgroup effects. METHOD A systematic literature search was performed (Medline, Embase and PsycINFO; 1975–2011) without language restrictions. Studies investigating the impact of post-MI depression on cardiovascular outcome, defined as all-cause mortality, cardiac mortality and cardiac events within 24 months after the index MI, were identified. Depression had to be assessed within 3 months after MI using established instruments. Pooled odds ratios (ORs) were calculated using a random effects model. RESULTS A total of 29 studies were identified, resulting in 41 comparisons. Follow-up (on average 16 months) was described for 16,889 MI patients. Post-MI depression was associated with an increased risk of all-cause mortality [(OR), 2.25; 95% confidence interval [CI], 1.73-2.93; P<.001], cardiac mortality (OR, 2.71; 95% CI, 1.68–4.36; P<.001) and cardiac events (OR, 1.59; 95% CI, 1.37-1.85; P<.001). ORs proved robust in subgroup analyses but declined over the years for cardiac events. CONCLUSIONS Post-MI depression is associated with a 1.6- to 2.7-fold increased risk of impaired outcomes within 24 months. This association has been relatively stable over the past 25 years.

Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study

BACKGROUND Residual depressive symptomatology constitutes a substantial risk for relapse in depression. Treatment until full remission is achieved is therefore implicated. However, there is a lack of knowledge about the prevalence of (1) residual symptoms in general and (2) the individual residual symptoms in particular. METHOD In a 3-year prospective study of 267 initially depressed primary care patients we established per week the presence/absence of the individual DSM-IV depressive symptoms during subsequent major depressive episodes (MDEs) and episodes of (partial) remission. This was accomplished by means of 12 assessments at 3-monthly intervals with the Composite International Diagnostic Interview (CIDI). RESULTS In general, residual depressive symptomatology was substantial, with on average two symptoms present during remissions. Three individual symptoms (cognitive problems, lack of energy and sleeping problems) dominated the course of depression and were present 85-94% of the time during depressive episodes and 39-44% of the time during remissions. CONCLUSIONS Residual symptoms are prevalent, with some symptoms being present for almost half of the time during periods of remission. Treatment until full remission is achieved is not common practice, yet there is a clear need to do so to prevent relapse. Several treatment suggestions are made.

Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis

BACKGROUND The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. AIMS To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. METHOD An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. RESULTS Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. CONCLUSIONS The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.

Adjusted prognostic association of post-myocardial infarction depression withmortality and cardiovascular events: an individual patient data meta-analysis

BACKGROUND The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. AIMS To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. METHOD An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. RESULTS Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. CONCLUSIONS The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.

Enhanced treatment for depression in primary care: long-term outcomes of a psycho-educational prevention program alone and enriched with psychiatric consultation or cognitive behavioral therapy

BACKGROUND The long-term outcome of major depression is often unfavorable, and because most cases of depression are managed by general practitioners (GPs), this places stress on the need to improve treatment in primary care. This study evaluated the long-term effects of enhancing the GPs usual care (UC) with three experimental interventions. METHOD A randomized controlled trial was conducted from 1998 to 2003. The main inclusion criterion was receiving GP treatment for a depressive episode. We compared: (1) UC (n=72) with UC enhanced with: (2) a psycho-educational prevention (PEP) program (n=112); (3) psychiatrist-enhanced PEP (n=37); and (4) brief cognitive behavioral therapy followed by PEP (CBT-enhanced PEP) (n=44). We assessed depression status quarterly during a 3-year follow-up. RESULTS Pooled across groups, depressive disorder-free and symptom-free times during follow-up were 83% and 17% respectively. Almost 64% of the patients had a relapse or recurrence, the median time to recurrence was 96 weeks, and the mean Beck Depression Inventory (BDI) score over 12 follow-up assessments was 9.6. Unexpectedly, PEP patients had no better outcomes than UC patients. However, psychiatrist-enhanced PEP and CBT-enhanced PEP patients reported lower BDI severity during follow-up than UC patients [mean difference 2.07 (95% confidence interval (CI) 1.13-3.00) and 1.62 (95% CI 0.70-2.55) respectively] and PEP patients [2.37 (95% CI 1.35-3.39) and 1.93 (95% CI 0.92-2.94) respectively]. CONCLUSIONS The PEP program had no extra benefit compared to UC and may even worsen outcome in severely depressed patients. Enhancing treatment of depression in primary care with psychiatric consultation or brief CBT seems to improve the long-term outcome, but findings need replication as the interventions were combined with the ineffective PEP program.

Internal and external validity of the experiences in close relationships questionnaire in an american and two dutch samples

Background and objectives: The Experiences in Close Relationships scale (ECR) is much used in adult attachment research. In this study we examined: the psychometric properties of the Dutch ECR in comparison with the original American ECR; the claim of orthogonality of its scales Avoidance and Anxiety; and a broader applicability of the ECR, because much research is restricted to psychology student samples. Methods: In Study 1 we investigated the ECRs internal structure by means of confirmative factor analysis in the American psychology student sample in which the ECR was originally validated. We compared these findings with the results of factor analyses in: a Dutch psychology student sample to test whether the Dutch translation yields comparable results; and a Dutch general population sample to evaluate the Supposed orthogonality and to determine a broader applicability of the ECR. In Study 2 we evaluated aspects of the external validity of the ECR. Results: Confirmative factor analysis supports the original two factor structure in both Dutch samples, although less clear in the population sample. As opposed to both student samples the scales correlate moderately in the population sample. Results support external validity of the ECR in both Dutch samples. Conclusions: Since the supposed orthogonality of the scales varies by sample, the internal validity of the (Dutch) ECR varies by sample as well, namely from satisfactorily (population) to adequate (students). The external validity of the Dutch ECR is compared to the American version adequate, suggesting a broader applicability.

Short-term effects of enhanced treatment for depression in primary care : results from a randomized controlled trial

BACKGROUND Depression is a highly prevalent, often recurring or persistent disorder. The majority of patients are initially seen and treated in primary care. Effective treatments are available, but possibilities for providing adequate follow-up care are often limited in this setting. This study assesses the effectiveness of primary-care-based enhanced treatment modalities on short-term patient outcomes. METHOD In a randomized controlled trial we evaluated a psycho-educational self-management intervention. We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder, assessed by a structured psychiatric interview. Patients were randomly assigned to: the Depression Recurrence Prevention (DRP) program (n=112); a combination of the DRP program with psychiatric consultation (PC+DRP, n=39); a combination with brief cognitive behavior therapy (CBT+DRP, n=44); and care as usual (CAU, n=72). Follow-up assessments were made at 3 months (response 90%) and 6 months (85%). RESULTS Patient acceptance of enhanced care was good. The mean duration of the index episode was 11 weeks (S.D.=9.78) and similar in CAU and enhanced care. Recovery rate after 6 months was 67% overall; 17% of all participants remained depressed for the entire 6-month period. CONCLUSION Enhanced care did not result in better short-term outcomes. We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program. Observed depression treatment rates in CAU were high.

Self-reported depressive symptoms, diagnosed clinical depression and cardiac morbidity and mortality after myocardial infarction

BACKGROUND Self-reported depressive symptoms and clinical depression after myocardial infarction (MI) are both associated with poor cardiac prognosis. It is important to distinguish between the two when assessing cardiac prognosis, but few studies have done so. The present article evaluates the independent prognostic impact of self-reported depressive symptoms and clinical depression on cardiac outcomes after MI. METHODS 2704 MI-patients were administered the Beck Depression Inventory (BDI) and underwent the Composite International Diagnostic Interview at 3 months post-MI. All-cause mortality, cardiac mortality and cardiovascular readmissions were evaluated up till 10 years post-MI (mean: 6 years), representing 16,783 persons-years of follow-up. Event-free survival was evaluated using Cox regression analysis. RESULTS Analyses on mortality and cardiovascular readmissions included 2493 and 2434 patients respectively. Compared to patients scoring <5 on the BDI, those scoring ≥ 19 had age- and sex-adjusted HRs (95% CI) of 3.20 (2.16-4.74, p<0.001) for all-cause mortality, 3.97 (2.06-7.65, p<0.001) for cardiac mortality, and 1.45 (1.08-1.95, p<0.05) for cardiovascular readmissions. Cardiac disease severity and cardiac risk factors explained one third to half of the relationship. The presence of clinical depression was associated with all-cause (HR: 1.72 (1.29-2.30, p<0.001)) and cardiac mortality (HR: 1.67 (1.01-2.77, p<0.05)). However, adjusting for BDI-scores decreased these HRs with 53% and 72% respectively, rendering them non-significant. Dichotomized BDI-scores remained to predict cardiac prognosis independently from the presence of clinical depression. CONCLUSIONS After MI, self-reported depressive symptoms are a more accurate predictor of cardiac morbidity and mortality than clinical depression. This association is confounded largely by cardiac disease severity.

Cognitive-behavioural therapy v. usual care in recurrent depression

We examined in a primary care sample whether acute-phase cognitive-behavioural therapy (CBT) would be more effective than usual care for patients with multiple prior episodes of depression. Depression outcome was based on a 3-monthly administered Beck Depression Inventory (BDI) during a 2-year follow-up. We confirmed that in patients with four or more prior episodes, CBT outperformed usual care by four points on the BDI, but not in patients with three or fewer prior episodes. Subsequent analyses suggested that CBT may be able to tackle cognitive problems related to rumination in patients with recurrent depression.

Systematic Review and Individual Patient Data Meta-Analysis of Sex Differences in Depression and Prognosis in Persons With Myocardial Infarction: A MINDMAPS Study.

Objective Using combined individual patient data from prospective studies, we explored sex differences in depression and prognosis post–myocardial infarction (MI) and determined whether disease indices could account for found differences. Methods Individual patient data analysis of 10,175 MI patients who completed diagnostic interviews or depression questionnaires from 16 prospective studies from the MINDMAPS study was conducted. Multilevel logistic and Cox regression models were used to determine sex differences in prevalence of depression and sex-specific effects of depression on subsequent outcomes. Results Combined interview and questionnaire data from observational studies showed that 36% (635/1760) of women and 29% (1575/5526) of men reported elevated levels of depression (age-adjusted odds ratio = 0.68, 95% confidence interval [CI] = 0.60–0.77). The risk for all-cause mortality associated with depression was higher in men (hazard ratio = 1.38, 95% CI = 1.30–1.47) than in women (hazard ratio = 1.22, 95% CI = 1.14–1.31; sex by depression interaction: p < .001). Low left ventricular ejection fraction (LVEF) was associated with higher depression scores in men only (sex by LVEF interaction: B = 0.294, 95% CI = 0.090–0.498), which attenuated the sex difference in the association between depression and prognosis. Conclusions The prevalence of depression post-MI was higher in women than in men, but the association between depression and cardiac prognosis was worse for men. LVEF was associated with depression in men only and accounted for the increased risk of all-cause mortality in depressed men versus women, suggesting that depression in men post-MI may, in part, reflect cardiovascular disease severity.