Cognitive impairment and pregabalin dependence

Abouzed, Mohamed; Emam, Mahmoud Mohamed

doi:10.4103/ejpsy.ejpsy_34_19

Cited by 6 publications

(5 citation statements)

References 2 publications

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“…Previous studies showed that pregabalin has several neurotoxic effects with long-term use [ 13 , 14 ]. These negative effects have a significant deleterious impact on neurodevelopment and brain function in neurological and cognitive disorders [ 15 ]. The viability of neurons was not affected as compared to that of the controls ( Figure 2 A), which confirmed that this dose was not toxic to the cells.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons

Alsanie

Alhomrani

Gaber

et al. 2022

Cells

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Pregabalin is widely used as a treatment for multiple neurological disorders; however, it has been reported to have the potential for misuse. Due to a lack of safety studies in pregnancy, pregabalin is considered the last treatment option for various neurological diseases, such as neuropathic pain. Therefore, pregabalin abuse in pregnant women, even at therapeutic doses, may impair fetal development. We used primary mouse embryonic neurons to investigate whether exposure to pregabalin can impair the morphogenesis and differentiation of ventral midbrain neurons. This study focused on ventral midbrain dopaminergic neurons, as they are responsible for cognition, movement, and behavior. The results showed that pregabalin exposure during early brain development induced upregulation of the dopaminergic progenitor genes Lmx1a and Nurr1 and the mature dopaminergic gene Pitx3. Interestingly, pregabalin had different effects on the morphogenesis of non-dopaminergic ventral midbrain neurons. Importantly, our findings illustrated that a therapeutic dose of pregabalin (10 μM) did not affect the viability of neurons. However, it caused a decrease in ATP release in ventral midbrain neurons. We demonstrated that exposure to pregabalin during early brain development could interfere with the neurogenesis and morphogenesis of ventral midbrain dopaminergic neurons. These findings are crucial for clinical consideration of the use of pregabalin during pregnancy.

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Section: Resultsmentioning

confidence: 99%

The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons

Alsanie

Alhomrani

Gaber

et al. 2022

Cells

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“…Cav2.2 is also upregulated in demyelinating areas [ 103 ], but its blocker pregabalin, prescribed to treat neuropathic pain in MS patients [ 62 , 63 ], might rise concerns about memory impairment, as it decreases LTP in mice and working memory in humans [ 63 , 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, in the same paper, the authors pointed to a significant reduction of hippocampal long-term potentiation in pregabalin-treated EAE mice, thus warning of potential side effects on memory and learning processes [ 58 , 63 ]. In accordance with deleterious effects on memory, two recent clinical studies showed that perioperative pregabalin reduced spatial working memory in humans [ 64 ] and its misuse led to cognitive impairment [ 65 ].…”

Section: Voltage-gated Channels In Oligodendroglial Cells and Myelinationmentioning

confidence: 99%

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

Cherchi

Bulli

Venturini

et al. 2021

IJMS

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Multiple sclerosis (MS) is the most demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation. Oligodendrocyte progenitor cells (OPCs) are cycling cells in the developing and adult CNS that, under demyelinating conditions, migrate to the site of lesions and differentiate into mature oligodendrocytes to remyelinate damaged axons. However, this process fails during disease chronicization due to impaired OPC differentiation. Moreover, OPCs are crucial players in neuro-glial communication as they receive synaptic inputs from neurons and express ion channels and neurotransmitter/neuromodulator receptors that control their maturation. Ion channels are recognized as attractive therapeutic targets, and indeed ligand-gated and voltage-gated channels can both be found among the top five pharmaceutical target groups of FDA-approved agents. Their modulation ameliorates some of the symptoms of MS and improves the outcome of related animal models. However, the exact mechanism of action of ion-channel targeting compounds is often still unclear due to the wide expression of these channels on neurons, glia, and infiltrating immune cells. The present review summarizes recent findings in the field to get further insights into physio-pathophysiological processes and possible therapeutic mechanisms of drug actions.

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“…However, this study had a small sample size and short follow-up duration without a control group ( Shem et al, 2018 ). A cross-sectional study, including 300 patients with pregabalin misuse and 100 controls, showed greater cognitive impairment in the patient group than in the control group ( p < .001) ( Mohamed and Emam, 2020 ). In this study, no association was determined between the dose of pregabalin and cognitive impairment ( Mohamed and Emam, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…A cross-sectional study, including 300 patients with pregabalin misuse and 100 controls, showed greater cognitive impairment in the patient group than in the control group ( p < .001) ( Mohamed and Emam, 2020 ). In this study, no association was determined between the dose of pregabalin and cognitive impairment ( Mohamed and Emam, 2020 ). In a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set, gabapentin initiation in cognitively normal older adult research volunteers (age ≥65 years; 480 initiators; 4,320 nonusers) was significantly associated with deleterious neurocognitive changes in the 2 years after initiation ( Oh et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan

2023

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Objective: Previous studies have shown that gabapentin or pregabalin use is associated with cognitive decline. Herein, we aimed to evaluate the association between gabapentin or pregabalin use and the risk of dementia.Methods: In this retrospective, population-based matched cohort study, all research data were collected from the 2005 Longitudinal Health Insurance Database, which contains data of 2 million people randomly selected from the National Health Insurance Research Database of Taiwan in 2005. The study extracted data from 1 January 2000, to 31 December 2017. Adult patients taking gabapentin or pregabalin were included in the exposure group, and patients not using gabapentin or pregabalin matched to exposure subjects in a 1:5 ratio by propensity scores composed of age, sex and index date were included in the non-exposure group.Results: A total of 206,802 patients were enrolled in the study. Of them, 34,467 gabapentin- or pregabalin-exposure and 172,335 non-exposure patients were used for analysis. The mean follow-up day (±standard deviation) after the index date was 1724.76 (±1282.32) and 1881.45 (±1303.69) in the exposure and non-exposure groups, respectively; the incidence rates of dementia were 980.60 and 605.48 per 100,000 person-years, respectively. The multivariate-adjusted hazard ratio of risk of dementia for gabapentin or pregabalin exposure versus the matched non-exposed group was 1.45 (95% confidence interval [CI], 1.36–1.55). The risk of dementia increased with higher cumulative defined daily doses during the follow-up period. Moreover, the stratification analysis revealed that the risk of dementia associated with gabapentin or pregabalin exposure was significant in all age subgroups; however, it was higher in younger patients (age <50) than in the older patients (hazard ratio, 3.16; 95% CI, 2.23–4.47).Conclusion: Patients treated with gabapentin or pregabalin had an increased risk of dementia. Therefore, these drugs should be used with caution, particularly in susceptible individuals.

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Cognitive impairment and pregabalin dependence

Cited by 6 publications

References 2 publications

The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons

The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan

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