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The pooled estimates of the association between antidepressant use and the risk of dementia. The red dot indicates the point estimate of the risk ratio (RR), and the black line indicates the confidence interval (CI). The pooled RR was 1.21 (95% CI 1.12–1.29), indicating that the use of antidepressants was associated with an increased risk of dementia. The heterogeneity across the included studies was moderate to high (I² = 71%) [36,37,38,39,40,41].
Source publication
Depression, commonly treated with antidepressants, is associated with an increased risk of dementia, especially in older adults. However, the association between antidepressant use and dementia risk is unclear. We searched for randomized controlled trials and observational studies from PubMed, Embase, and Cochrane on 1 February 2022, restricting to...
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Background
Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered...
Background
The diagnosis and treatment of head and neck cancer (HNC) is associated with several life-altering morbidities including change in appearance, speech, and swallowing, all of which can significantly affect quality of life and cause psychosocial stress.
Commentary
The aim of this narrative review is to provide an overview of the evidence...
Major depressive disorder, a common and complex disorder, has its onset associated with many factors. Common management includes antidepressant agents, together with psychotherapy in severe cases, but a significant percentage of patients do not improve. The urgency of newer approaches is a need, and clinical trials are studying the role of magnesiu...
Citations
... Antidepressants, particularly those from classes like SSRIs and SNRIs, have shown great potential in mitigating cognitive decline in individuals with both major depressive disorder and early dementia [12]. A systematic review of 43 randomized controlled trials revealed that antidepressants offer cognitive benefits, likely due to a combination of neuroprotective mechanisms. ...
... Notably, some antidepressants, fluoxetine, citalopram, and amitriptyline, have been implicated in reducing the build-up of β-amyloid plaques, which are closely linked to Alzheimer's disease pathology [105]. This multifaceted approach supports the recognition of antidepressants as beneficial in managing cognitive symptoms of dementia and potentially slowing its progression, as detailed below (Table 2) [12,90,[104][105][106][107]. Table 2. Various antidepressants and their neuroprotective effects [90]. ...
... This association is particularly concerning due to the well-documented severe side effects, including postural hypotension and urinary retention, which present further safety risks in older adults. Furthermore, it is worth mentioning that TCAs block muscarinic acetylcholine receptors in the CNS, key players in cognitive function, further amplifying the risk of neurocognitive decline [12,28]. Considering these risks, the 2023 American Geriatrics Society Beers Criteria strongly advises against the use of antidepressants with potent anticholinergic properties, such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, and paroxetine, in older adults with dementia or cognitive impairment. ...
The coexistence of dementia and depression in older populations presents a complex clinical challenge, with each condition often exacerbating the other. Cognitive decline can intensify mood disturbances, and untreated or recurring depression accelerates neurodegenerative processes. As depression is a recognized risk factor for dementia, it is crucial to address both conditions concurrently to prevent further deterioration. Antidepressants are frequently used to manage depression in dementia patients, with some studies suggesting they offer neuroprotective benefits. These benefits include promoting neurogenesis, enhancing synaptic plasticity, and reducing neuroinflammation, potentially slowing cognitive decline. Additionally, antidepressants have shown promise in addressing Alzheimer’s-related pathologies by reducing amyloid-beta accumulation and tau hyperphosphorylation. However, treatment-resistant depression remains a significant challenge, particularly in older adults with cognitive impairment. Many do not respond well to standard antidepressant therapies due to advanced neurodegenerative changes. Conflicting findings from studies add to the uncertainty, with some research suggesting that antidepressants may increase dementia risk, especially when used in patients with undiagnosed early-stage dementia. This article aims to explore the intricate relationship between depression and dementia, examining the benefits and risks of antidepressant use. We highlight the urgent need for personalized, comprehensive treatment strategies that balance mental health improvement with cognitive protection.
... 19 Several systematic reviews and meta-analyses on the topic have also indicated that antidepressant use is associated with an increased risk of dementia. 6,[20][21][22] Contrarily, a study using large health insurance claims data in over 100 million records identified mirtazapine (a TCA antidepressant) as one of the medications associated with a reduction in the risk of dementia. 23 Another retrospective study using data from a German registry, a 10-year observation window, and a head-to-head comparison of antidepressants identified a risk reduction effect for antidepressants and suggested differences when comparing SSRI versus SNRI. ...
INTRODUCTION
The use of antidepressants in major depressive disorder (MDD) has been reported to influence long‐term risk of Alzheimer's disease (AD) and AD‐related dementias (AD/ADRD), but studies are conflicting.
METHODS
We used inverse probability weighted (IPW) Cox models with time‐varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022.
RESULTS
A total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events = 1,056, hazard ratio = 0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small.
DISCUSSION
Our study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention.
Highlights
We studied whether antidepressant use was associated with future dementia risk.
We specifically focused on patients after their first‐ever diagnosis of depression.
We used IPW Cox models with time‐varying covariates and a large observation window.
Our study did not identify an effect of antidepressant use on dementia risk.
A risk reduction was observed in female patients, but the number of cases was small.
Central nervous system (CNS)–active medication use is common in older adults; however, there are limited data on utilization trends over time, differences in utilization amongst those with and without dementia, and modification of utilization surrounding dementia diagnosis.
To evaluate CNS-active medication trends in US older adults with and without dementia over 13 years, including evaluation of changes in utilization before and after dementia diagnosis.
Retrospective observational cohort study using de-identified administrative claims data.
Older adult (age ≥ 65 years) commercial and Medicare Advantage enrollees with continuous medical and pharmacy coverage for at least one calendar year from 2010 through 2022.
(1) Annual probability of receiving CNS-active medications; (2) changes in medication use with dementia diagnosis.
In total, 6,062,601 enrollees were included; 682,833 (11.3%) with dementia and 5,379,768 (88.7%) without. CNS-active medication use was highest in those with dementia throughout the study time period. Opioid utilization in those with and without dementia was 36.1% and 29.6% in 2010, decreasing to 24.3% and 22.2%, respectively, in 2022. Antidepressant use increased over time (i.e., 45.2 to 52.0% dementia; 15.8 to 24.6% without). Antipsychotic use in those with dementia was 18.1% in 2010, decreased to 15.9% in 2016, and increased back to 18.0% in 2022. A total of 444,587 enrollees experienced incident dementia diagnosis. There were immediate increases in antipsychotic (0.9% [0.5, 1.4] absolute increase, p < 0.001) and antidepressant (4.0% [3.3, 4.6] absolute increase, p < 0.001) use in the month following diagnosis. Increased use of these medications peaked 3–5 years after diagnosis. Dementia diagnosis was associated with decreased slopes of opioid (− 0.2% [− 0.3, − 0.1], p < 0.001) and benzodiazepine (− 0.07% [− 0.11, − 0.03], p < 0.001) use.
CNS-active medication use is higher in older adults with dementia when compared to those without dementia. Incident dementia diagnosis is accompanied by marked increases in the use of antidepressants and antipsychotics.
Psychotropic drugs are vital in psychiatry, aiding in the management of mental health disorders. Their use requires an understanding of their pharmacological properties, therapeutic applications, and potential side effects. Ongoing research aims to improve their efficacy and safety. Biomarkers play a crucial role in understanding and predicting memory decline in psychotropic drug users. A comprehensive understanding of biomarkers, including neuroimaging, biochemical, genetic, and cognitive assessments, is essential for developing targeted interventions and preventive strategies. In this narrative review, we performed a comprehensive search on PubMed and Google using review-specific terms. Clinicians should use a multifaceted approach, including neurotransmitter analysis, neurotrophic factors, miRNA profiling, and cognitive tasks for early intervention and personalized treatment. Anxiolytics' mechanisms involve various neurotransmitter systems and emerging targets. Research on biomarkers for memory decline in anxiolytic users can lead to early detection and intervention, enhancing clinical practices and aligning with precision medicine. Mood stabilizer users can benefit from early detection of memory decline through RNA, neurophysiological, and inflammatory biomarkers, promoting timely interventions. Performance-enhancing drugs may boost athletic performance in the short term, but their long-term health risks and ethical issues make their use problematic. Long-term use of psychotropic performance enhancers in athletes shows changes in biomarkers of cognitive decline, necessitating ongoing monitoring and intervention strategies. Understanding these genetic influences on memory decline helps pave the way for personalized approaches to prevent or mitigate cognitive deterioration, emphasizing the importance of genetic screening and early interventions based on an individual's genetic profile. Future research should focus on refining these biomarkers and protective measures against cognitive deterioration. Overall, a comprehensive understanding of biomarkers in psychotropic drug users is essential for developing targeted interventions and preventive strategies.
Dementia is an umbrella term for a broad group of age‐associated neurodegenerative diseases. It is estimated that dementia affects 50 million people worldwide and that Alzheimer's disease (AD) is responsible for up to 75% of cases. Small extracellular senile plaques composed of filamentous aggregates of amyloid β (Aβ) protein tend to bind to neuronal receptors, affecting cholinergic, serotonergic, dopaminergic and noradrenergic neurotransmission, leading to neuroinflammation, among other pathophysiologic processes and subsequent neuronal death, followed by dementia. The amyloid cascade hypothesis points to a pathological process in the cleavage of the amyloid precursor protein (APP), resulting in pathological Aβ. There is a close relationship between the pathologies that lead to dementia and depression. It is estimated that depression is prevalent in up to 90% of individuals diagnosed with Parkinson's disease, with varying severity, and in 20 to 30% of cases of Alzheimer's disease. The hypothalamic pituitary adrenal (HPA) axis is the great intermediary between the pathophysiological mechanisms in neurodegenerative diseases and depression. This review discusses the role of Aβ protein in the pathophysiological mechanisms of dementia and depression, considering the HPA axis, neuroinflammation, oxidative stress, signalling pathways and neurotransmission.
