Is Antidepressant Treatment Associated with Reduced Cognitive Decline in Alzheimer’s Disease?

Mossello, Enrico; Boncinelli, Marta; Caleri, Veronica; Cavallini, Maria Chiara; Palermo, Eliana; Bari, Mauro Di; Tilli, Sabrina; Sarcone, Eva; Simoni, David; Biagini, Carlo; Masotti, Giulio; Marchionni, Niccolò

doi:10.1159/000121334

Cited by 48 publications

(37 citation statements)

References 80 publications

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“…Mossello et al mentioned that antidepressant treatment would protect cognitive function in depressed older patients with AD [54]. They further suggested that cognitive protection was possibly via a reduction in depressive symptoms after taking antidepressants, while we proposed that antidepressant medication might increase the risk of dementia independent of depression.…”

Section: Discussionmentioning

confidence: 65%

Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan

et al. 2017

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Depression and dementia are common mental health problems and are associated in several ways. Early-life depression is associated with increased risk of later life dementia, and depression can present as a preclinical symptom or consequence of dementia. Despite the plausible relationship between these two clinical entities, the potential association between antidepressant medication and dementia has rarely been investigated. We conducted a 9-year retrospective analysis of Taiwan’s National Health Insurance Research Database (NHIRD), enrolling 5819 cases who had received prescriptions of antidepressants between 2003 and 2006, and 23,276 (with ratio of 1:4) age, sex, and index date-matched controls. The hazard ratio (HR) of dementia among antidepressant users with depression was 2.42 (95% confidence interval (CI): 1.15–5.10), for those without depression was 4.05 (95% CI: 3.19–5.15), compared to antidepressant non-users respectively. Among the 6 classes of common antidepressants used in Taiwan, the adjusted HRs were 3.66 (95% CI: 2.62–5.09) for SSRIs, 4.73 (95% CI: 2.54–8.80) for SNRI, 3.26 (95% CI: 2.30–4.63) for TCAs, 6.62 (95% CI: 3.34–13.13) for TeCA, 4.94 (95% CI: 2.17–11.24) for MAOI, and 4.48 (95% CI: 3.13–6.40) for SARI. Furthermore, the multivariate analysis result showed that the adjusted HRs of cumulative defined daily doses (cDDDs) were 3.74 (95% CI: 2.91–4.82), 3.73 (95% CI: 2.39–5.80) and 5.22 (95% CI: 3.35–8.14) for those who had cDDDs of <90, 90–180 and >180 compared to those who had taken no antidepressant medication. This is a retrospective study based on secondary data, hence, we could not claim causality between antidepressant medication and dementia. However, a potential association between antidepressant and occurrence of dementia after controlling for the status of depression was observed. Lack of patients’ data about smoking status and body mass index in NHIRD, which are considered related to dementia, was also a limitation in this study. In this study, we concluded that antidepressant medication is a potential risk factor for dementia, independent from any effect of depression itself.

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Section: Discussionmentioning

confidence: 65%

Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan

et al. 2017

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“…The evidence for cognitive effect of antidepressant drugs is even weaker. Observational data support a reduced cognitive decline associated with antidepressants in patients with AD treated with CIs [Mossello et al 2008] and a pilot clinical trial has shown a beneficial effect of the association between selective serotonin reuptake inhibitors and CIs on functional status and clinical global impression [Mowla et al 2007]. However, taking into account the increased risk of adverse events linked to antidepressant treatment and the high response rate observed with placebo, the use of antidepressants in patients with AD has little support from a QoL perspective, except in the case of severe symptoms.…”

Section: Psychotropic Medicationsmentioning

confidence: 90%

Management of patients with Alzheimer’s disease: pharmacological treatment and quality of life

Mossello¹,

Ballini

2012

Therapeutic Advances in Chronic Disease

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Abstract:A methodological approach to quality of life (QoL) assessment in Alzheimer's disease (AD) is challenging and few clinical trials have included it among outcomes, with conflicting results. In this review an indirect appraisal of evidence has been performed, searching the literature for the effect of drug treatments on determinants of QoL in AD. Among clinical factors associated with QoL, possible targets of drugs include cognition, which seems to be associated with QoL in early disease and can be positively affected by cholinesterase inhibitors (CIs) in this stage; functional decline, the risk of which can be decreased by CIs and memantine (MEM); behavioral and psychological symptoms, which can be reduced by MEM and atypical antipsychotics. Long-term observational studies have associated CIs and MEM treatment with a reduced institutionalization risk. According to the evidence, drug treatment of depression associated with AD should not be first choice from a QoL perspective, while treatment of pain can have beneficial effects on wellbeing indicators also in the late stages of the disease. Possible drug-related adverse events can affect QoL and should always be weighed against expected benefits from the patient's perspective. For this reason antipsychotic treatment is often problematic in AD and should be limited to severe psychosis and aggression, using the lowest effective doses for the shortest possible period. Conversely titration of CIs is necessary to reach the most effective dosages, although dose-related risk of adverse events has to be taken into account. Finally, CIs and MEM have been shown to reduce caregiver burden in randomized trials, possibly affecting caregivers' QoL.

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“…In advanced AD, different serotonin receptor agonists show promising effects in enhancing memory and learning capacity according to clinical and animal studies [92,98]. In the same line, administration of serotonin re-uptake inhibitors improved memory function in AD patients [99]. Additionally, deficits in serotonergic innervation, serotonin transporters and tryptophan hydroxylase may contribute to anxiety and changes in waking/sleep cycle seen in AD [100,101].…”

Section: Dorsal Raphe Nucleus and The Serotonergic Systemmentioning

confidence: 99%

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Theofilas

Dunlop

Heinsen

et al. 2015

JAD

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Pharmacological interventions in Alzheimer's disease (AD) are likely to be more efficacious if administered early in the course of the disease, foregoing the spread of irreversible changes in the brain. Research findings underline an early vulnerability of the isodendritic core (IC) network to AD neurofibrillary lesions. The IC constitutes a phylogenetically conserved subcortical system including the locus coeruleus in pons, dorsal raphe nucleus and substantia nigra in the midbrain, and nucleus basalis of Meynert in basal forebrain. Through their ascending projections to the cortex, the IC neurons regulate homeostasis and behavior by synthesizing aminergic and cholinergic neurotransmitters. Here we reviewed the evidence demonstrating that neurons of the IC system show neurofibrillary tangles in the earliest stages of AD, prior to cortical pathology, and how this involvement may explain pre-amnestic symptoms, including depression, agitation and sleep disturbances in AD patients. In fact, clinical and animal studies show a significant reduction of AD cognitive and behavioral symptoms following replenishment of neurotransmitters associated with the IC network. Therefore, the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in AD.

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Is Antidepressant Treatment Associated with Reduced Cognitive Decline in Alzheimer’s Disease?

Cited by 48 publications

References 80 publications

Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan

Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan

Management of patients with Alzheimer’s disease: pharmacological treatment and quality of life

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

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