Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors

Rozzini, Luca; Chilovi, Barbara Vicini; Conti, Marta Zaffira; Bertoletti, Erik; Zanetti, Marina; Trabucchi, Marco; Padovani, Alessandro

doi:10.1017/s1041610209990184

Cited by 49 publications

(38 citation statements)

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“…Moreover, rats treated with the TCA amitriptyline from middle to old age had their water maze performance preserved compared with aged controls (Yau et al 2002). In depressed patients affected by AD and treated with AChEIs, Rozzini et al (2010) found that SSRIs might exert some degree of protection against the negative effects of depression on cognition. The present findings also demonstrated that treatment with donepezil resulted in a decrease of latency time in Morris water maze, thereby suggesting that the AlCl 3 -induced spatial learning deficits are related to cholinergic system impairment by the metal.…”

Section: Discussionmentioning

confidence: 98%

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

et al. 2014

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Alzheimer's disease is the leading cause of dementia in the elderly. Depression is a common psychiatric disorder affecting individuals across life span and often arises in the context of pre-dementia, dementia, and Alzheimer's disease. The present study aimed to investigate the effects of the antidepressant drugs clomipramine (14.2 and 56.9 μmol/kg), fluoxetine (14.5 and 57.8 μmol/kg), and sertraline (14.6 and 58.4 μmol/kg) compared with acetylcholinesterase inhibitor donepezil (12 μmol/kg) on oxidative stress, memory impairment, and depressant-like behavior in a model of Alzheimer's disease induced by prolonged intraperitoneal administration of aluminum chloride (AlCl 3 ) (10 mg/kg/day for 60 days) in rats. Results indicated that the latency to find the hidden platform in Morris water maze (MWM) test increased by 100 %, while the immobility duration in forced swimming test (FST) increased by 51 % in AlCl 3 -treated rats. The administration of AlCl 3 resulted in increased brain malondialdehyde (MDA) by 58.6 % and nitric oxide (nitrite) concentrations by 71.7 %, while reduced glutathione (GSH) decreased by 35.6 % compared with the vehicle-treated group. Catalase and paraoxonase 1 (PON1) activities in the brain decreased by 41.8 and 18.3 %, respectively. Serum acetylcholinesterase (AChE) increased by 47.8 % and brain butyrylcholinesterase (BuChE) decreased by 23.1 % after AlCl 3 treatment. In AlCl 3 -treated rats, memory performance in the MWM test improved following donepezil and the highest dose of clomipramine, fluoxetine, and sertraline. The immobility duration in the FST was decreased by sertraline. Significant decrease in brain MDA occurred after treatment with clomipramine, fluoxetine, and a lower dose of sertraline. Reduced glutathione level increased by donepezil, clomipramine, and 57.8 μmol/kg fluoxetine. The level of nitric oxide decreased by donepezil (42.6 %), clomipramine (45.0 and 62.9 %), fluoxetine (21.9 and 40.9 %), and 14.6 μmol/kg sertraline (28.7 %). Catalase activity was restored by donepezil, fluoxetine, and sertraline and markedly increased by 56.9 μmol/kg clomipramine. Paraoxonase 1 activity was increased by 14.2 μmol/kg clomipramine. BuChE activity was unaltered, but AChE activity was decreased by donepezil, clomipramine, and fluoxetine compared with the AlCl 3 control group. AlCl 3 resulted in neurodegeneration (gliosis), extensive dark neurons with corkscrew dendrites, and degeneration of some Purkinje cell. Following donepezil treatment, no dark neurons were observed, while increased granular cell layer was observed after the administration of a high dose of clomipramine, fluoxetine, or sertraline. The results suggested that in rats treated with AlCl 3 , (i) donepezil, sertraline, clomipramine, and fluoxetine improve memory performance; (ii) sertraline was particularly effective in improving depressive-like behavior in this model and might be of value in the treatment of depressive symptoms associated with Alzheimer's disease; (iii) donepezil, clomipramine, and fluoxetine alleviated oxi...

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Section: Discussionmentioning

confidence: 98%

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

et al. 2014

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“…A chronic treatment with SSRIs is associated with lower cortical β-amyloid PET signal in cognitively normal elderly human subjects (Cirrito et al, 2011), and with some degree of protection against the negative effects of depression on cognition in AD patients (Rozzini et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Fluoxetine Prevents Aβ1-42-Induced Toxicity via a Paracrine Signaling Mediated by Transforming-Growth-Factor-β1

et al. 2016

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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. At therapeutic concentrations (100 nM–1 μM), fluoxetine significantly prevented Aβ-induced toxicity in mixed glia-neuronal cultures, but not in pure neuronal cultures. Though to a lesser extent, also sertraline was neuroprotective in mixed cultures, whereas serotonin (10 nM–10 μM) did not mimick fluoxetine effects. Glia-conditioned medium collected from astrocytes challenged with fluoxetine protected pure cortical neurons against Aβ toxicity. The effect was lost in the presence of a neutralizing antibody against TGF-β1 in the conditioned medium, or when the specific inhibitor of type-1 TGF-β1 receptor, SB431542, was added to pure neuronal cultures. Accordingly, a 24 h treatment of cortical astrocytes with fluoxetine promoted the release of active TGF-β1 in the culture media through the conversion of latent TGF-β1 to mature TGF-β1. Unlike fluoxetine, both serotonin and sertraline did not stimulate the astrocyte release of active TGF-β1. We conclude that fluoxetine is neuroprotective against Aβ toxicity via a paracrine signaling mediated by TGF-β1, which does not result from a simplistic SERT blockade.

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“…Findings also suggest that in treatment of AD patients with cholinesterase inhibitors and SSRIs may offer some degree of protection against the adverse effects of depression on cognition (47). Tricyclic antidepressants are not recommended due to the poor side effects profile.…”

Section: Discussionmentioning

confidence: 99%

“…Reviews indicated that antidepressants (mainly SSRIs) not only showed efficacy in treating BPSD, but were also well tolerated (47,51). Two out of five studies of sertraline versus placebo and one study of sertraline versus haloperidol have shown benefit.…”

Section: Antidepressantsmentioning

confidence: 99%

Medications used in dementia: a review of evidence

Suraweera

Hanwella²,

Silva

2015

Sri Lanka J. Psyc.

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Medications used in dementia: a review of evidence psychological symptoms of dementia (BPSD), and has also being considered for the treatment of dementias of lesser severity.Evidence also supports the use of AChE inhibitors in vascular dementia and dementia due to Parkinson's disease (PDD). But evidence regarding efficacy in dementia of Lewy Body (DLB) is not very strong.Antipsychotics can be used for the management of BPSD if other measures fail, keeping in mind the black box warning for the risk of stroke. The use of antidepressants and mood stabilisers are limited by the lack of strong evidence. ConclusionThe current evidence supports the use of cholinesterase inhibitors and memantine in patients with Alzheimer's dementia, vascular dementia and PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. SL J Psychiatry 2015; 6(2): 3-8 BackgroundDementia is an acquired global impairment of intellect, memory and personality, without impairment of consciousness. It is usually progressive in nature. The management of dementia is mainly two faceted; pharmacological and non-pharmacological. AimsTo review the evidence regarding the efficacy of cholinesterase inhibitors, memantine and antipsychotics, in the treatment of dementia. MethodsWe searched ALOIS, Cochrane database, PubMed, Scopus and Google scholar using key words; dementia, cognitive enhancers, cholinesterase inhibitors and memantine as individual words for relevant review articles. ResultsThere is evidence of efficacy of donepezil, rivastigmine and galantamine in mild to moderate Alzheimer's dementia (AD). Evidence also suggests that memantine has efficacy in moderate to severe AD. Further, memantine may benefit behavioural and

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Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors

Abstract: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

Cited by 49 publications

References 26 publications

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

Study of the effect of antidepressant drugs and donepezil on aluminum-induced memory impairment and biochemical alterations in rats

Fluoxetine Prevents Aβ1-42-Induced Toxicity via a Paracrine Signaling Mediated by Transforming-Growth-Factor-β1

Medications used in dementia: a review of evidence

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