Do antiepileptic drugs increase the risk of infectious diseases? A meta‐analysis of placebo‐controlled studies

Zaccara, Gaetano; Giovannelli, Fabio; Giorgi, Filippo Sean; Franco, Valentina; Gasparini, Sara; Tacconi, Francesco Mandò

doi:10.1111/bcp.13296

Cited by 19 publications

(18 citation statements)

References 30 publications

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“…Levetiracetam, an analogue of BRV, has the same mechanism of action as BRV, and these two antiepileptic drugs exert their anti-epileptic effects through binding to SV2A (8). With regard to the infectious disease, a meta-analysis suggests that application of BRV alone does not increase the risk of infectious disease (25), which is consistent with the present results. That study also pointed out that levetiracetam is associated with a significantly higher risk of infectious diseases than BRV (25).…”

Section: Discussionsupporting

confidence: 90%

Comparison of the safety of brivaracetam at various doses among patients with epilepsy: A network meta‑analysis of randomized controlled trials

Meng

Shi

et al. 2020

Exp Ther Med

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The present study aimed to compare the safety of brivaracetam (BRV) at various doses among patients with epilepsy through a network meta-analysis. Randomized controlled trials (RCTs) were retrieved from different databases, which were then pooled for a network analysis for calculating the odds ratios (ORs), together with the corresponding 95% confidence intervals (CIs) and surface under the cumulative ranking curve (SUCRA). A total of 9 RCTs were included in the final analysis. Compared with placebo, BRV at a dose of 50 mg daily led to a markedly increased risk of nervous system disorders (OR, 0.62; 95% CI, 0.43-0.90; P=0.01) and evidently increased the risk of psychiatric disorders (OR, 0.16; 95% CI, 0.04-0.64; P=0.022). However, BRV treatment was not associated with a statistically significant change in the prevalence of infectious diseases. SUCRA analysis suggested that treatment with BRV at 50 mg/day posed the highest risk of nervous system disorders and psychiatric disorders compared with placebo or other doses of BRV. In conclusion, BRV treatment at a dose of 50 mg/day may increase the risk of nervous system diseases and psychosis disorders compared with the placebo group. However, more high-quality clinical studies are warranted to validate these results.

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Section: Discussionsupporting

confidence: 90%

Comparison of the safety of brivaracetam at various doses among patients with epilepsy: A network meta‑analysis of randomized controlled trials

Meng

Shi

et al. 2020

Exp Ther Med

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“…Those drugs are not only administered for epilepsy and can be useful in a wide spectrum of disorders, although some have been associated with a modest increased risk of infectious diseases. 15 It remains unknown whether patients with epilepsy have an increased risk of COVID-19 or developing more severe disease. 16,17 The aim of this study was to determine the incidence and fatality of COVID-19 among patients with active epilepsy compared with the general population, identify the main risk factors related to higher fatality in patients with active epilepsy, and analyze whether epilepsy is associated with fatality in hospitalized patients with COVID-19.…”

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confidence: 99%

Incidence and case fatality rate of COVID-19 in patients with active epilepsy

et al. 2020

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OBJECTIVEThis article estimates the incidence and fatality of COVID-19 and identify potential risk factors to fatality in patients with active epilepsy.MATERIAL AND METHODSThis is a cross-sectional observational study of patients with active epilepsy and COVID-19. A control group was used to compare the cumulative incidence and case fatality rate (CFR). The main outcomes of the study were cumulative incidence, defined as number of patients with active epilepsy and COVID-19 admitted in emergency department divided by the total number of patients with epilepsy at risk; and CFR based on the number of deaths during the enrolment period. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with active epilepsy.RESULTSOf the 1537 patients who fulfilled the inclusion criteria, 21 (1.3%) had active epilepsy. The cumulative incidence (95% CI) of COVID-19 in epilepsy patients was higher (1.2% [0.6-2.4]) compared to population without epilepsy (0.5% [0.5-0.5]). In RT-PCR positive patients there were no significant differences in CFR in patients with active epilepsy compared to patients without epilepsy (33.3% vs. 8.3%; p =0.266). Of the 21 active epilepsy patients, 5 (23%) died. In multivariate analysis, the factor associated with fatality in patients with active epilepsy was hypertension (OR [95%CI], 2.8 [1.3-21.6]). In other model age (OR [95%CI], 1.0 [1.0-1.1]) and epilepsy (OR [95%CI], 5.1 [1.3-24.0]) were associated with fatality during hospitalization.CONCLUSIONCOVID-19 cumulative incidence were higher in patients with active epilepsy. Epilepsy was associated with fatality during hospitalization. Hypertension was associated with fatality in patients with epilepsy.

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“…It is well known that valproate can cause reversible bone marrow suppression leading to leukopenia and neutropenia (Acharya and Bussel 2000 ). However, a meta-analysis of infectious diseases reported as adverse events during the double-blind phase of placebo-controlled randomized clinical studies failed to show a significant effect of valproate (Zaccara et al 2017 ). It should be noted, however, that groups treated with lithium or valproate are likely to differ in several respects (Additional file 1 : Table S1).…”

Section: Discussionmentioning

confidence: 99%

Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

Landén

Larsson

Lichtenstein

et al. 2021

Int J Bipolar Disord

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Background In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment. Conclusions This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.

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Do antiepileptic drugs increase the risk of infectious diseases? A meta‐analysis of placebo‐controlled studies

Abstract: Some AEDs are associated with a mild increased risk of infection.

Cited by 19 publications

References 30 publications

Comparison of the safety of brivaracetam at various doses among patients with epilepsy: A network meta‑analysis of randomized controlled trials

Comparison of the safety of brivaracetam at various doses among patients with epilepsy: A network meta‑analysis of randomized controlled trials

Incidence and case fatality rate of COVID-19 in patients with active epilepsy

Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

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