A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC).

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwards selection to determine predictor variables while allowing non-linear relations, to develop a prediction model for depression outcome post-ECT (and logistic regression for remission and response as secondary outcome measures). Internal validation and internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. In total, 1892 adult patients with MDD were included from 22 clinical and research cohorts of the twelve sites within the Dutch ECT Consortium. The final primary prediction model showed several factors that significantly predicted a lower depression score post-ECT: higher age, shorter duration of the current depressive episode, severe MDD with psychotic features, lower level of previous antidepressant resistance in the current episode, higher pre-ECT global cognitive functioning, absence of a comorbid personality disorder, and a lower level of failed psychotherapy in the current episode. The optimism-adjusted R² of the final model was 19%. This prediction model based on readily available clinical information can reduce uncertainty of ECT outcomes and hereby inform clinical decision-making, as prompt referral for ECT may be particularly beneficial for individuals with the above-mentioned characteristics. However, despite including a large number of pretreatment factors, a large proportion of the variance in depression outcome post-ECT remained unpredictable.

A prospective study into change of vitamin D levels, depression and frailty among depressed older persons.

OBJECTIVES: While vitamin D is involved in frailty as well as depression, hardly any study has examined the course of vitamin D levels prospectively. The objective of this study is to examine whether a change of vitamin D in depressed older adults is associated with either depression course, course of frailty, or both. METHODS: The study population consisted of 232 of 378 older adults (60-93 years) with a DSM-IV defined depressive disorder participating in the Netherlands Study of Depression in Older persons, a prospective clinical cohort study. Baseline and 2-year follow-up data on depressive disorder (DSM-IV diagnosis), symptom severity (inventory of depressive symptoms), frailty phenotype (and its individual components) and vitamin D levels were obtained. Linear mixed models were used to study the association of change in vitamin D levels with depression course, course of frailty, and the combination. RESULTS: Vitamin D levels decreased from baseline to follow-up, independent from depression course. An increase in frailty was associated with a significantly sharper decrease of vitamin D levels over time. Post hoc analyses showed that this association with frailty might be driven by an increase of exhaustion over time and counteracted by an increase in walking speed. CONCLUSIONS: Our findings generate the hypothesis that vitamin D supplementation in late-life depression may improve frailty, which may partly explain inconsistent findings of randomised controlled trials evaluating the effect of vitamin D for depression. We advocate to consider frailty (components) as an outcome in future supplementation trials in late-life depression.

Clinical characteristics of late-life depression predicting mortality.

OBJECTIVE: Depression has been associated with increased mortality rates, and modifying mechanisms have not yet been elucidated. We examined whether specific subtypes or characteristics of late-life depression predict mortality. METHODS: A cohort study including 378 depressed older patients according to DSM-IV criteria and 132 never depressed comparisons. The predictive value of depression subtypes and characteristics on the six-year mortality rate, as well as their interaction with somatic disease burden and antidepressant drug use, were studied by Cox proportional hazard analysis adjusted for demographic and lifestyle characteristics. RESULTS: Depressed persons had a higher mortality risk than non-depressed comparisons (HR = 2.95 [95% CI: 1.41-6.16], p = .004), which lost significance after adjustment for age, sex, education, smoking, alcohol, physical activity, number of prescribed medications and somatic comorbidity. Regarding depression subtypes and characteristics, only minor depression was associated with a higher mortality risk when adjusted for confounders (HR = 6.59 [95% CI: 1.79-24.2], p = .005). CONCLUSIONS: Increased mortality rates of depressed older persons seem best explained by unhealthy lifestyle characteristics and multiple drug prescriptions. The high mortality rate in minor depression, independent of these factors, might point to another, yet unknown, pathway towards mortality for this depression subtype. An explanation might be that minor depression in later life reflects depressive symptoms due to underlying aging-related processes, such as inflammation-based sickness behavior, frailty, and mild cognitive impairment, which have all been associated with increased mortality.

Vitamin D deficiency and course of frailty in a depressed older population.

Objective: To study the association between vitamin D levels and frailty, its components and course in a depressed sample.Methods: Baseline and two-year follow-up data from the depressed sample of the Netherlands Study of Depression in Older persons (NESDO), a prospective observational cohort study, were analyzed. The 378 participants (aged 60-93) had a diagnosis of depression according to DSM-IV criteria. Frailty was defined according to Fried's physical phenotype. 25-OH vitamin D measurement was performed by liquid chromatography - tandem mass spectrometry. Linear and logistic regression analyses were performed, adjusted for covariates.Results: Higher vitamin D levels were cross-sectionally associated with lower prevalence of frailty (OR 0.64 [95%-CI 0.45 - 0.90], p = .010), predicted a lower incidence of frailty among non-frail depressed patients (OR 0.51 [95%-CI 0.26 - 1.00], p=.050), and, surprisingly, the persistence of frailty among frail depressed patients (OR 2.82 [95%-CI 1.23 - 6.49], p=.015).Conclusions: In a depressed population, higher vitamin D levels were associated with lower prevalence and incidence of frailty. Future studies should examine whether the favorable effect of low vitamin D levels on the course of frailty can be explained by confounding or whether unknown pathophysiological mechanisms may exert protective effects.

Sarcopenic obesity predicts nonremission of late-life depression.

BACKGROUND/OBJECTIVES: Aging-related physiological changes like metabolic dysregulation and physical frailty are associated with depression and worsen its prognosis. Since central obesity is a key component of the metabolic syndrome and sarcopenia of physical frailty, we examined the association of sarcopenic obesity with depression cross-sectional and over time. METHODS: Cohort study of depressed patients and a nondepressed comparison group. SETTING: Primary and secondary mental health care. PARTICIPANTS: Three hundred seventy-eight older (≥60 y) depressed patients of which 285 were followed up at 2 years and 132 nondepressed persons participating in the Netherlands Study of Depression in Older (NESDO) persons. MEASUREMENTS: Sarcopenic obesity was based on predefined cutoffs for both maximum handgrip strength (assessed with a dynamometer) and waist circumference (dichotomous) as well as the product term of handgrip strength by waist circumference (dimensional). Depressive disorder according to DSM-IV-TR criteria was assessed with fully structured psychiatric interview at baseline and 2-year follow-up. RESULTS: Sarcopenic obesity was more prevalent among depressed patients compared with nondepressed participants (18.9% versus 10.7%, P = 0.030). Neither the dichotomous nor dimensional operationalization of sarcopenic obesity was associated with baseline depressive disorder when adjusted for covariates. Nonetheless, among depressed patients, logistic regression showed that the interaction of handgrip strength by waist circumference was associated with remitted depression at 2-year follow-up (P = 0.044). Only among patients with a low handgrip strength, a higher waist circumference predicted nonremission. CONCLUSION: Among depressed patients, sarcopenic obesity predicts nonremission of depression. Therefore, combined exercise and nutritional interventions might be effective for depressed patients with sarcopenic obesity.

Electroconvulsive Therapy as a Powerful Treatment for Delirium: A Case Report.

OBJECTIVE: The aim of the study was to describe the successful treatment of delirium with electroconvulsive therapy (ECT). METHODS: The method of the study was a case report. RESULTS: A 75-year-old man, with a recently diagnosed carcinoma of the parotid gland, was admitted with a fluctuating psychiatric syndrome. Delirium was diagnosed, although an acute underlying somatic cause could not be readily established. Antipsychotics and benzodiazepines were not effective. After 7 sessions of ECT, all symptoms ceased. This enabled him to receive radiotherapy for his tumor and enjoy a good quality of life for the remaining 8 months of his life. CONCLUSIONS: Electroconvulsive therapy is not only a powerful treatment for catatonia, neuroleptic malignant syndrome, and delirious mania but also for the most commonly occurring fluctuating psychiatric syndrome--delirium.

Adverse health outcomes in vitamin D supplementation trials for depression: A systematic review.

BACKGROUND: Vitamin D deficiency is a universal risk factor for adverse health outcomes. Since depression is consistently associated with low vitamin D levels as well as several adverse health outcomes, vitamin D supplementation may be especially relevant for depressed persons. This review examines the potential benefits of vitamin D for (somatic) health outcomes in randomised controlled supplementation trials for depression. METHOD: Systematic literature search to assess whether adverse health outcomes, such as frailty, falls, or cognitive functioning, were included in vitamin D supplementation trials for depression, and whether these outcomes were affected by supplementation. The revised Cochrane tool for assessing risk of bias in randomised trials was used. RESULTS: Thirty-one trials were included. Adverse health outcomes were considered in five studies. Two studies reported some beneficial effect on an adverse health outcome. CONCLUSIONS AND IMPLICATIONS: While depressed persons are at increased risk of vitamin D deficiency, supplementation trials hardly addressed the common negative health consequences of low vitamin D levels as secondary outcome measures. Well-designed trials of the effects of vitamin D supplementation in late-life depression should explore whether adverse health outcomes can be prevented or stabilised, and whether depression benefits from this improvement.

Frailty as a Predictor of Mortality in Late-Life Depression: A Prospective Clinical Cohort Study.

OBJECTIVE: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients. METHODS: In our study of 378 older patients aged ≥ 60 years with a depressive disorder (DSM-IV criteria), we examined whether frailty predicts time-to-death during a 6-year follow-up using Cox proportional hazard regression analyses adjusted for confounders. Baseline data were collected from 2007 to September 2010. Frailty was defined according to the Fried Frailty Phenotype criteria (muscle weakness, slowness, exhaustion, low activity level, unintended weight loss). Similarly, we examined the predictive value of 3 inflammatory markers, vitamin D level, and leukocyte telomere length and whether these effects were independent of the frailty phenotype. RESULTS: During follow-up, 27 (26.2%) of 103 frail depressed patients died compared with 35 (12.7%) of 275 non-frail depressed patients (P < .001). Adjusted for confounders, the number of frailty components was associated with an increased mortality rate (hazard ratio = 1.38 [95% CI, 1.06-1.78], P = .015). All biomarkers except for interleukin 6 were prospectively associated with mortality, but only higher levels of high-sensitivity C-reactive protein and lower levels of vitamin D were independent of frailty associated with mortality. CONCLUSIONS: In late-life depression, frailty identifies older patients at increased risk of adverse negative health outcomes. Therefore, among frail depressed patients, treatment models that include frailty-specific interventions might reduce mortality rates.

Vitamin D deficiency, depression course and mortality: Longitudinal results from the Netherlands Study on Depression in Older persons (NESDO).

OBJECTIVE: To study the effect of vitamin D levels on depression course and remission status after two years, as well as attrition and mortality, in an older cohort. METHODS: This study was part of the Netherlands Study on Depression in Older persons (NESDO), a prospective cohort study. 367 depressed older persons (≥ 60 years) were included. Baseline vitamin D status, reasons for loss to follow up, clinical depression diagnosis at two-year follow up, and six-monthly symptom scores were obtained. Data were analyzed by logistic regression and random coefficient models and adjusted for confounders of vitamin D status. RESULTS: Vitamin D had no effect on the course of depression or remission, except for a trend towards lower remission rates in the severely deficient subgroup (25-(OH) vitamin D<25 nmol/l). Patients who died during follow up had significantly lower 25-(OH) vitamin D and 1,25-(OH)2 vitamin D levels than patients with continued participation. CONCLUSIONS: For the total sample we found no effect of vitamin D levels on the course of depression or remission rates. However, we did find an effect of lower vitamin D levels on mortality. This strengthens the interpretation of vitamin D deficiency being a marker for poor somatic health status. The trend towards lower remission rates in the severely deficient subgroup raises the question whether this group could benefit from supplementation. Randomized controlled trials are necessary to study this.