Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Abstract

Background Vinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn’t find conclusive evidence favoring its use, two more RCTs have also been completed. Methods Relevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration’s tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson’s I 2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger’s test. We used a random effect model when I 2 was more than 50% and a fixed-effect model for other parameters. Results Four placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65–0.99 and relative risk 0.67, CI 0.48–0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03–0.95 and SMD 1.22, CI 0.23–2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02–1.82, p = 0.04). Conclusions Vinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-022-01499-y.

Unauthorized ingredients in “nootropic” dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents

“…Vinpocetine is indicated as an adjuvant treatment for chronic CNS disorders of cerebral circulation in the elderly, impairment of hearing, neurological disorders such as memory disorders, and post‐stroke impairment. It also improves vision disorders associated with impaired circulation of the choroid and retina of the eye 88,110–112 …”

“…Inhibition of phosphodiesterases (PDEs) in the cells of vascular walls causes an increase in the concentration of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and, consequently, relaxation of smooth muscles and vasodilation. Vinpocetine is well absorbed from the gastrointestinal tract with approximately 60% absorption, and its biological half‐life is estimated to be 5–6 h. In the human body, vinpocetine is metabolized primarily by the liver into apovincaminic acid 110–112 …”

“…Potential adverse effects related to vinpocetine treatment include sleep disturbances (insomnia), dizziness, flushing to the head, heartburn, changes in blood pressure (primarily lowering), and electrocardiogram changes such as ST depression, QT prolongation, or tachycardia. Caution should be exercised when using vinpocetine concomitantly with other drugs, primarily antiarrhythmic, and anticoagulant drugs such as drugs that influence the CNS, including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and sympathomimetic drugs (decongestants, OTC cold, and flu medicines including phenylephrine or pseudoephedrine) 110–112 . The cross‐reactivity of vinpocetine with a variety of substances increases the potential to cause harm or public health risks in certain circumstances.…”

The role of Phosphodiesterase-1 and its natural product inhibitors in Alzheimer’s disease: A review

“…Given this situation, vinpocetine has not been accepted by clinicians for universal routine use for any neurological disorder. A systematic review found promising yet inconclusive evidence favoring its use in patients with dementia ( Panda et al, 2022 ). The discovery of a novel, natural, and nontoxic treatment for AD remains a great need ( Nabavi et al, 2019 ).…”

“…These effects were found in geriatrics who were affected by vascular dementia in the subcortical region and need to be elucidated in large-scale trials with other groups ( Tomassoni et al, 2008 ). A double-blinded study recommended the routine prescription of vinpocetine; however, vinpocetine has not progressed to placebo-controlled randomized clinical trials with a particular sample size ( Panda et al, 2022 ). Vinpocetine remains extensively used as a nootropic owing to its memory-boosting effect, which may be correlated with its vasodilating effect.…”