Iatrogenic depression in the elderly. Results from a community-based study in the Netherlands

Background. The aim of this study was to investigate the association between the use of medication and depression in the elderly. Method. A cross-sectional population-based study was conducted. Associations between the use of medication and depression are corrected for eight other etiological correlates of depression. The sample consisted of 2646 elderly people living in 11 municipalities in the Netherlands. Subjects were taken from the Longitudinal Aging Study Amsterdam, a 10-year longitudinal study on predictors and consequences of changes in well-being and autonomy in the older population. Associations are expressed in odds ratios (95% Confidence Intervals) between the use of (groups of) medication and depression. Results are adjusted for age, sex, urbanicity, socioeconomic status, physical health, social and interpersonal support, comorbidity with other psychiatric disease and personality. The Population Attributable Risk percentage wag calculated for selected groups of medication. Results. After correction for competing risk factors of depression, 22 individual medications and nine groups of medications had unique associations with depression. Conclusions. The use of depressogenic medication is an independent etiological factor in the pathogenesis of depression

Study design of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) project; a cohort study of older patients with affective disorders referred for specialised geriatric mental health care

BackgroundAffective disorders, encompassing depressive-, anxiety-, and somatic symptom disorders, are the most prevalent mental disorders in later life. Treatment protocols and guidelines largely rely on evidence from RCTs conducted in younger age samples and ignore comorbidity between these disorders. Moreover, studies in geriatric psychiatry are often limited to the younger old and rarely include the most frail. Therefore, the effectiveness of treatment in routine clinical care for older patients and impact of ageing characteristics is largely unknown.ObjectiveThe primary aim of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) - project is to examine the impact of ageing characteristics on the effectiveness of treatment for affective disorders in specialised geriatric mental health care.MethodsROM-GPS is a two-stage, multicentre project. In stage one, all patients aged 60years referred to participating outpatient clinics for specialised geriatric mental health care will be routinely screened with a semi-structured psychiatric interview, the Mini International Neuropsychiatric Interview and self-report symptom severity scales assessing depression, generalized anxiety, hypochondria, and alcohol use. Patients with a unipolar depressive, anxiety or somatic symptom disorder will be asked informed consent to participate in a second (research) stage to be extensively phenotyped at baseline and closely monitored during their first year of treatment with remission at one-year follow-up as the primary outcome parameter. In addition to a large test battery of potential confounders, specific attention is paid to cognitive functioning (including computerized tests with the Cogstate test battery as well as paper and pencil tests) and physical functioning (including multimorbidity, polypharmacy, and different frailty indicators). The study is designed as an ongoing project, enabling minor adaptations once a year (change of instruments).DiscussionAlthough effectiveness studies using observational data can easily be biased, potential selection bias can be quantified and potentially corrected (e.g. by propensity scoring). Knowledge of age-related determinants of treatment effectiveness, may stimulate the development of new interventions. Moreover, studying late-life depressive, anxiety and somatic symptom disorders jointly enables data-driven studies for more optimal classification of these disorders in later life.Trial registrationDutch Trial Register: NL6704 (www.trialregister.nl). Retrospectively registered on 2017-12-05

Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine : Study protocol for a pragmatic randomized controlled trial (CYSCEtrial)

Background: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. Methods/Design: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening. Discussion: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression

Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial)

Background: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. Methods/Design: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening. Discussion: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression