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Ssri alzheimer

Filippo Caraci, Fabio Tascedda, Sara Merlo, Cristina Benatti, Simona F Spampinato, Antonio Munafò, Gian Marco Leggio, Ferdinando Nicoletti, Nicoletta Brunello, Filippo Drago, Maria Angela Sortino, Agata Copani
Selective reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, increase circulating Transforming-Growth-Factor-β1 (TGF-β1) levels in depressed patients, and are currently studied for their neuroprotective properties in Alzheimer's disease. TGF-β1 is an anti-inflammatory cytokine that exerts neuroprotective effects against β-amyloid (Aβ)-induced neurodegeneration. In the present work, the SSRI, fluoxetine, was tested for the ability to protect cortical neurons against 1 μM oligomeric Aβ1-42-induced toxicity...
2016: Frontiers in Pharmacology
Louise Ørum Olesen, Elena V Bouzinova, Maurizio Severino, Mithula Sivasaravanaparan, Jørgen Bo Hasselstrøm, Bente Finsen, Ove Wiborg
Alzheimer's disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset of cognitive symptoms both in humans with early and late onset AD. The behavioural profile promoted by the AD pathology is believed to associate with degeneration of the serotonergic system. Using the APPswe/PS1δE9 model of AD-like pathology starting with 9 months old mice, we characterised long term non-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests...
2016: PloS One
Shelly L Gray, Joseph T Hanlon
Use of medications with anticholinergic activity is widespread in older adults. Several studies have highlighted that anticholinergic use may be associated with an increased risk of dementia. The objective of this narrative review is to describe and evaluate studies of anticholinergic medication use and dementia and provide practical suggestions for avoiding use of these medications in older adults. A comprehensive review of the literature, citations from recent reviews and the author's personal files was conducted...
October 2016: Therapeutic Advances in Drug Safety
L Zhou, S L Ma, P K K Yeung, Y H Wong, K W K Tsim, K F So, L C W Lam, S K Chung
Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear...
2016: Translational Psychiatry
Jonathan R Fisher, Clare E Wallace, Danielle L Tripoli, Yvette I Sheline, John R Cirrito
BACKGROUND: The aggregation of amyloid-β (Aβ) into insoluble plaques is a hallmark pathology of Alzheimer's disease (AD). Previous work has shown increasing serotonin levels with selective serotonin re-uptake inhibitor (SSRI) compounds reduces Aβ in the brain interstitial fluid (ISF) in a mouse model of AD and in the cerebrospinal fluid of humans. We investigated which serotonin receptor (5-HTR) subtypes and downstream effectors were responsible for this reduction. RESULTS: Agonists of 5-HT4R, 5-HT6R, and 5-HT7R significantly reduced ISF Aβ, but agonists of other receptor subtypes did not...
2016: Molecular Neurodegeneration
Walid Tajeddinn, Torbjörn Persson, Javier Calvo-Garrido, Mohammed Seed Ahmed, Silvia Maioli, Swetha Vijayaraghavan, Mehmet Selim Kazokoglu, Cristina Parrado-Fernández, Takashi Yoshitake, Jan Kehr, Paul Francis, Bengt Winblad, Kina Höglund, Angel Cedazo-Minguez, Dag Aarsland
Serotonin (5-HT) plays a central role in the integrity of different brain functions. The 5-HT homeostasis is regulated by many factors, including serotonin transporter (SERT), monoamine oxidase enzyme (MAO), and several 5-HT receptors, including the 5-HT1B. There is little knowledge how the dynamics of this system is affected by the amyloid-β (Aβ) burden of Alzheimer's disease (AD) pathology. SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of Aβ pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist...
May 7, 2016: Journal of Alzheimer's Disease: JAD
Pan Luo, Xiaoxue Zhang, Yun Lu, Cheng Chen, Changjun Li, Mei Zhou, Qing Lu, Xulin Xu, Guanxin Shen, Lianjun Guo
Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO)...
January 2016: Pharmacology, Biochemistry, and Behavior
Hyung-Mun Yun, Kyung-Ran Park, Eun-Cheol Kim, Sanghyeon Kim, Jin Tae Hong
Alzheimer's disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of Aβ via the inhibition of γ-secretase activity and the inactivation of astrocytes and microglia in the AD mouse model...
September 29, 2015: Oncotarget
Shana A Nelson, Gerri A Wilson, Michelle Tucci, Hamed Benghuzzi
Recent reports in the literature show an increase in the risk of heart related events in patients treated with tricyclic antidepressants. There is also evidence that serotonin reuptake inhibitors (SSRIs) are negatively associated with heart failure. The objective of our study is to determine if cardiomyocytes in culture can be used as a tool to mimic clinical scenarios and to evaluate therapeutic concentrations of SSRIs (fluoxetine) and antidiabetic (troglitazone) medication. Cardiomyocytes were grown in a tissue culture environment and challenged with therapeutic concentrations of SSRIs alone or a combination of SSRIs and antidiabetic drugs...
2015: Biomedical Sciences Instrumentation
Xin Du, Terence Y Pang
There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression...
2015: Frontiers in Psychiatry
Damien Gallagher, Nathan Herrmann
Agitation and aggression are prevalent in Alzheimer's disease and have significant consequences for the patient, caregiver and care system more generally. We briefly discuss the epidemiology and etiology of agitation and aggression in Alzheimer's disease and provide an overview of assessment and approaches to care. We then review the evidence for and against a number of pharmacological and psychosocial approaches to care. There has been a growth in the evidence base for psychosocial interventions and nonpharmacological approaches to care should ordinarily be the first option...
2015: Neurodegenerative Disease Management
Anton P Porsteinsson, Jessica S Smith, Melanie A Keltz, Inga M Antonsdottir
Neuropsychiatric symptoms (NPS) are a major concern in the treatment of Alzheimer's disease. Historically, NPS are difficult to treat effectively due to a high side-effect burden associated with commonly used medications, such as atypical antipsychotics. Non-pharmacological treatment approaches have become the first line option. However, when such treatment fails, pharmacological options are often used. Thus, a push toward finding safer alternative pharmacological treatments has occurred. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) have shown promise in clinical trials for alleviating the burden of NPS...
September 2014: Expert Review of Neurotherapeutics
Yvette I Sheline, Tim West, Kevin Yarasheski, Robert Swarm, Mateusz S Jasielec, Jonathan R Fisher, Whitney D Ficker, Ping Yan, Chengjie Xiong, Christine Frederiksen, Monica V Grzelak, Robert Chott, Randall J Bateman, John C Morris, Mark A Mintun, Jin-Moo Lee, John R Cirrito
Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer's disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor, decreased Aβ in brain interstitial fluid in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of preexisting plaques and reduced the appearance of new plaques by 78%...
May 14, 2014: Science Translational Medicine
Laia Calvó-Perxas, Oriol Turró-Garriga, Maria Aguirregomozcorta, Josep Bisbe, Erélido Hernández, Secundino López-Pousa, Anna Manzano, Mónica Palacios, Imma Pericot-Nierga, Héctor Perkal, Lluís Ramió, Joan Vilalta-Franch, Josep Garre-Olmo
OBJECTIVES: Psychotropic drugs are usually prescribed to deal with behavioral and psychological symptoms of dementia, especially when nonpharmacologic approaches are not available or have limited efficacy. Poor outcomes and serious adverse events of the drugs used must be addressed, and risk-benefit ratios need to be considered. The aim of this longitudinal study was to describe the evolution of dispensation of psychotropic drugs in patients with Alzheimer's disease (AD) and to identify the associated demographic and clinical variables...
July 2014: Journal of the American Medical Directors Association
Aaron M Koenig, Meryl A Butters, Amy Begley, Semhar Ogbagaber, Abdus S Wahed, Charles F Reynolds
OBJECTIVE: Late-life depression frequently co-occurs with cognitive impairment. To inform clinical management of these conditions, we examined the hypotheses that, relative to cognitively normal elders meeting DSM-IV criteria for major depressive disorder, those with cognitive impairment would require greater intensity of pharmacotherapy to reach criteria for antidepressant response and would take longer to respond. METHOD: Using data from the MTLD-3 study, we conducted a series of secondary analyses examining the implications of cognitive impairment for short-term, open-trial pharmacotherapy of late-life depression (major depressive disorder in individuals 65 years and older)...
February 2014: Journal of Clinical Psychiatry
Nathan Herrmann, Krista L Lanctôt, David B Hogan
BACKGROUND: While there have been no new medications approved for the treatment of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) reviewed and updated the clinical practice guidelines on the pharmacological management of dementia that were published previously. METHODS: This review focused on the literature for the pharmacological treatment of dementia based on studies published since the third CCCDTD in 2006...
July 8, 2013: Alzheimer's Research & Therapy
Rolin L Wade, Sylvia L Kindermann, Qingjiang Hou, Michael E Thase
BACKGROUND: Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression. OBJECTIVES: To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder...
January 2014: Journal of Managed Care Pharmacy: JMCP
Aiesha Ahmed, Zachary Simmons
Pseudobulbar affect (PBA) may occur in association with a variety of neurological diseases, and so may be encountered in the setting of amyotrophic lateral sclerosis, extrapyramidal and cerebellar disorders, multiple sclerosis, traumatic brain injury, Alzheimer's disease, stroke, and brain tumors. The psychological consequences and the impact on social interactions may be substantial. Although it is most commonly misidentified as a mood disorder, particularly depression or a bipolar disorder, there are characteristic features that can be recognized clinically or assessed by validated scales, resulting in accurate identification of PBA, and thus permitting proper management and treatment...
2013: Therapeutics and Clinical Risk Management
Amir A Sepehry, Philip E Lee, Ging Yuek R Hsiung, B Lynn Beattie, Claudia Jacova
BACKGROUND: Comorbid depression is a leading neuropsychiatric complication in the Alzheimer's disease (AD) syndrome. In 2011, diagnostic criteria for AD were revised to include neuropsychiatric symptoms. It has been proposed that adding an antidepressant to existing treatment for AD could provide relief for not only depressive but also cognitive symptoms. OBJECTIVE: The aim was to quantitatively review published studies to examine the efficacy of selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) therapy for alleviation of comorbid, diagnosed depression as well as cognitive decline in AD...
October 2012: Drugs & Aging
M Ujeyl, B Müller-Oerlinghausen
BACKGROUND: Treatment of depression in palliative care must take into account expected benefits and risks of antidepressants in patients with potentially limited life expectancy, poor medical condition, advanced age and higher risk to suffer from side effects and drug interactions. This systematic review assesses evidence of the efficacy and safety of different classes of antidepressants depending on the type and severity of the physical illness. METHODS: A systematic database search (Medline, EMBASE) for clinical studies was carried out and references of identified literature were checked...
September 2012: Der Schmerz
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