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User:Puduḫepa/SSRIs and cognitive functions

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SSRIs' negative effects

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"Some studies have reported the effects of SSRIs on cognitive functions, but the results are conflicting.(...)It seems that the use of SSRIs in patients with depression or OCD, can cause cognitive dysfunction in the acute phase of treatment.(...)Originally, SSRIs did not appear to cause cognitive impairment, but nowadays there are conflicting evidences regarding this side effect and many patients complain of memory loss during their course of therapy with SSRIs [4, 5].(...) he study by Popovic et al. showed that over 20% of patients with depression or anxiety disorders reported memory loss after 6 months of SSRI therapy. This was considered a side effect rather than a symptom of untreated depression/anxiety [21] (...)wo other case reports with memory loss subsequent to fluoxetine use have been published in previous years. In one case report, memory loss was reversed when fluoxetine was changed to another SSRI [23, 24]. Although memory impairments can be due to depression itself, memory loss appears to be more likely due to SSRI therapy rather than depression symptoms. Serretti et al. showed that using SSRIs even in healthy individuals leads to cognitive impairment [25]. The memory loss caused by SSRIs has not yet been convincingly explained; however, serotonin appears to play an important role in learning and memory [26]. Serotonin transporter (SERT) expression has been found to be vital for memory development. Decreased expression of this transporter was found in Alzheimer's disease and other memory impairments and dementia [27]"

″his paper describes a 14-year-old male patient who complained of memory problems during treatment with fluoxetine for major depression. The patient showed impairments on all five scales of the Wechsler Memory Scale-Revised during fluoxetine treatment. Three of the scales, Verbal Memory, Visual Memory, and General Memory, showed statistically significant improvements after fluoxetine was discontinued. This case represents the first time memory deficits related to fluoxetine were quantitated with a standardized memory test. It points to cognitive side effects that need to be understood.″

"Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood" + "During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention. After dosing was discontinued, sustained attention, recognition memory and cognitive flexibility were evaluated. "

  • https://www.sciencedaily.com/releases/2011/03/110316084425.htm —"both beneficial effects and side effects can persist after treatment is stopped." + "The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress. Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity. Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus."

"...The most notable of these has been the effect on sexual functioning. Less well-known, yet clinically significant, are movement disturbances that can occur with SSRI use. This should be of concern to clinicians, as movement disorders are uncomfortable, can adversely impact compliance, and can undermine the alliance between clinician and patient."

"both beneficial effects and side effects can persist after treatment is stopped." + "The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress. Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity. Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus."

"We showed that acute escitalopram administration impaired learning and cognitive flexibility, but improved the ability to inhibit responses in stop-signal trials while leaving unaffected acute emotional processing. Our findings suggest a dissociation of effects of acute escitalopram on cognitive functions, possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits."

SSRIs' positive effects

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"Verbal memory impairment in schizophrenia is associated with abnormalities in gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF) systems. Recent evidence from animal and clinical studies that adding fluvoxamine to antipsychotics alters the expression of transcripts encoding for the GABA-A receptor and BDNF led us to postulate that fluvoxamine augmentation may improve memory in schizophrenia."

  • https://www.medicalnewstoday.com/articles/323339.php — "Recently, researchers from the University of Waterloo in Ontario, Canada, have found a surprising mechanism at play, namely that SSRIs appear to inhibit the growth of dementia-specific aggregates in the brain."

"In our study, cognitive and psychomotor functions are improved in the fluoxetine-treated group, this improvement is highly significant as compared to the baseline score of the same group. These findings are significant and of clinical importance.(...) Finding of the study supports the concept that long-term use of fluoxetine does not impair memory and psychomotor function but improves it significantly."

  • https://www.ncbi.nlm.nih.gov/pubmed/17224716 —″In several studies, selective serotonin reuptake inhibitors demonstrated promotion of neurogenesis in the hippocampus.″ + ″Fluoxetine enhanced memory and cognition in the patients. This was consistent with previous studies that emphasized the role of fluoxetine in improving memory and promoting neurogenesis in the hippocampus. However, this is a preliminary study with SMALL sample size, and larger double-blind placebo-controlled studies are needed to confirm these findings.″

″These results suggest that (R)-fluoxetine, which has been reported to have a shorter half-life than (S)-fluoxetine, has superior antidepressant effects and more consistently improves spatial learning and memory. This profile offers advantages in depression treatment and may also aid management of the neurocognitive impairments associated with depression.″

″Fluoxetine may potentially improve cognition in patients with vascular dementia and requires further investigation″

  • https://www.intechopen.com/books/health-and-academic-achievement/influence-of-drugs-on-cognitive-functions "(...)Similar effects were observed with fluoxetine (serotonin reuptake inhibitor); rats receiving a chronic treatment of fluoxetine increased cell proliferation and BDNF in hippocampus associated to a memory and learning improvement [83]. These studies suggest that antidepressants revert memory and learning deterioration observed in animal models of depression (...) Regarding clinical studies, patients with major depressive disorder showed lower levels of BDNF in plasma, which correlates with memory function deficits; hence, BDNF levels increased after the antidepressant treatment [84]. Nevertheless, the impairment in psychomotor and memory processes observed in depressed treated patients has no significance for clinical purposes [85]. Moreover, some evidence has shown that conventional antidepressant treatment selectively diminishes cognitive dysfunction [86]. The involvement of antidepressant drugs in cognitive functions is not clear; however, animal model studies have shown that synaptic plasticity is increased in neuronal regions involved in mood and memory processing [81, 82, 83, 84]."

"The effect of SSRIs on hippocampal function remains poorly defined. While SSRIs have the potential to normalize hippocampal plasticity under stress conditions and to treat mood symptoms in MDD, their effects on cognitive function are less clear. Since SSRIs do not possess selectivity for 5-HT receptor subtypes, their efficacy might be weakened due to opposing activities of different 5-HT receptor subtypes. In this context, multitarget drugs or combination therapies might be a better strategy to modulate both emotional and cognitive processes in the hippocampus. Future insights into interactions between different serotonergic subtypes might therefore lead to novel treatment options for the treatment of MDD."

Paraphrase

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