Depression in older people with and without dementia : non-pharmacological interventions and associations between psychotropic drugs and mortality

Abstract: The aim of this thesis was to investigate associations between psychotropic drug use and death, associations between functional capacity, dependency in ADL and depression, and to evaluate a non-pharmacological intervention to reduce depressive symptoms, among older people with and without dementia.There is limited knowledge about the risk of death associated with psychotropic drug use among those aged ≥85 years, those with dementia, or those living in residential care facilities; groups that have a higher intake of psychotropic drugs and who are also more prone to adverse drug reactions. In a representative sample of people ≥85 years (n = 992), baseline antidepressant use was not associated with an increased 5-year mortality risk when adjusting for confounding factors. A significant interaction between gender and antidepressant use was found, with a higher mortality risk in women, than in men.  When analyzing men and women separately, no significant associations were found. In a sample of older people (i.e. ≥65 years) with dementia (n = 1037), there was a significant gender difference in 2-year mortality associated with the baseline use of antidepressant drugs, with a lower mortality risk in men, than in women. In men, the mortality risk was significantly reduced with antidepressant use, while there was no significant association in women. The association between baseline use of benzodiazepines and mortality had a tendency toward an increased risk during the first year of follow-up, although this became non-significant after adjustments. In this time period, the interaction term for sex was significant, with a higher mortality risk among men than women. When the sexes were analyzed separately, no significant associations were found. No significant associations were found between baseline use of antipsychotic drugs and mortality.Drug treatment for depression seems to have a limited effect in older people and may have no effect in people with dementia. In order to find alternative ways of treating or preventing depression in older age, it is important to increase our knowledge about factors associated with this condition. Functional capacity and dependency in activities of daily living (ADL) are associated with depression in community-dwelling older people. However, it is uncertain whether the same associations are to be found in very old people (i.e. ≥80 years), including those with severe cognitive or physical impairments. In a heterogeneous sample (n = 392) with a high mean age, a large range of cognitive and functional capacity, a wide spectrum of dependency in ADL, and a high prevalence of comorbidities, depressive symptoms were significantly associated with functional balance capacity, but not with overall dependency in ADL. Among individual ADL tasks, dependency in transfer and dressing were associated with depressive symptoms.Physical exercise has shown effect sizes similar to those of antidepressants in reducing depressive symptoms among older people without dementia, with moderate–high-intensity exercise being more effective than low-intensity exercise. However, these effects are unclear among older people with dementia. Care-facility residents with dementia (n = 186) were cluster-randomized to a high-intensity functional exercise program or a non-exercise control activity conducted for 45 minutes every other weekday for 4 months. No significant difference between the exercise and control activity was found in depressive symptoms at 4 or 7 months. Among participants with high levels of depressive symptoms, reductions were observed in both the exercise and control groups at 4 and 7 months.In conclusion, ongoing treatment at baseline with any of the three psychotropic drug classes antidepressants, antipsychotics and benzodiazepines did not increase the risk of mortality in older people with dementia.  Neither did antidepressant drugs in very old people. In both samples, gender differences were found in the mortality risk due to antidepressant use. In those with dementia, the mortality risk due to benzodiazepine use also differed by gender. The potential risk from initial treatment and gender differences regarding mortality risk require further investigation in randomized controlled trials or in large cohort studies properly controlled for confounding factors. In older people, living in community and residential care facilities, functional capacity seems to be independently associated with depressive symptoms whereas overall ADL performance may not be associated. Dependency in the individual ADL tasks of transfer and dressing appear to be independently associated with depressive symptoms and may be an important focus for future interdisciplinary multifactorial intervention studies. Among older people with dementia living in residential care facilities, a 4-month high-intensity functional exercise program has no superior effect on depressive symptoms than a control activity. Both exercise and non-exercise group activities may reduce high levels of depressive symptoms. However, this finding must be confirmed in three-armed randomized controlled trials including control groups receiving standard care.