Lyrica and seizures
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Pregabalin (Lyrica) and Seizures: A Comprehensive Overview
Introduction to Pregabalin (Lyrica) and Its Uses
Pregabalin, commercially known as Lyrica, is a medication primarily used to treat neuropathic pain, partial-onset seizures, and generalized anxiety disorder. It is structurally related to gabapentin and works by binding to the alpha2-delta (α2-δ) subunit of voltage-gated calcium channels, which reduces the release of several neurotransmitters and decreases neuronal excitability2 3 4.
Mechanism of Action in Seizure Control
Alpha2-Delta Subunit Binding
Pregabalin's anticonvulsant properties are attributed to its high-affinity binding to the α2-δ subunit of voltage-gated calcium channels. This binding reduces the synaptic release of neurotransmitters, thereby decreasing neuronal excitability and preventing seizures2 3 4. Studies in rodent models have shown that pregabalin effectively inhibits various types of seizures, including tonic extensor seizures and clonic seizures induced by pentylenetetrazole4.
Neurotransmitter Modulation
Pregabalin subtly reduces the synaptic release of several neurotransmitters, which is believed to account for its ability to reduce neuronal excitability and seizures. This mechanism is consistent across various preclinical studies, indicating that pregabalin's efficacy in seizure control is closely linked to its interaction with the α2-δ subunit2 3 9.
Clinical Efficacy in Seizure Management
Adjunctive Therapy for Partial Seizures
Pregabalin has been approved in both the US and Europe as an adjunctive therapy for partial seizures in adults. Clinical trials have demonstrated that patients receiving pregabalin in doses ranging from 150 to 600 mg per day experienced significantly fewer seizures compared to those receiving a placebo6 7. The drug's efficacy in reducing seizure frequency makes it a valuable addition to existing antiepileptic regimens.
Case Studies and Real-World Evidence
A study conducted in an urban emergency department highlighted the potential risks associated with recreational abuse of pregabalin. Among the patients who presented after abusing the drug, 60% experienced seizures, with some requiring intensive care1. This underscores the importance of monitoring pregabalin use to prevent misuse and associated complications.
Safety and Tolerability
Common Adverse Effects
The most commonly reported adverse effects of pregabalin include somnolence, dizziness, and headache. These side effects were significant enough to cause withdrawal from clinical trials in up to 32% of patients6. Despite these adverse effects, pregabalin is generally well-tolerated when used as prescribed.
Serious Adverse Events
In rare cases, pregabalin use has been associated with more severe adverse events, such as hemorrhagic vasculitis. However, these instances are uncommon and typically occur in patients with other underlying health conditions7.
Conclusion
Pregabalin (Lyrica) is a potent antiepileptic drug that effectively reduces seizure frequency through its action on the α2-δ subunit of voltage-gated calcium channels. While it is generally well-tolerated, its potential for misuse and associated risks, such as seizures from recreational abuse, necessitate careful monitoring. Overall, pregabalin remains a valuable tool in the management of partial-onset seizures and other neurological conditions.
Sources and full results
Most relevant research papers on this topic
LYRICA NIGHTS–RECREATIONAL PREGABALIN ABUSE IN AN URBAN EMERGENCY DEPARTMENT
Pregabalin recreational abuse can lead to seizures and ICU admissions, requiring emergency physicians to be aware of its use and potential toxicity.
Case Report
Rigorous JournalPharmacology and mechanism of action of pregabalin: The calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery
Pregabalin reduces neuronal excitability and seizures by binding to the alpha2–delta subunit of voltage-gated calcium channels, potentially through reduced neurotransmitter release.
Highly CitedPharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery.
Pregabalin reduces neuronal excitability and seizures by binding to alpha2-delta subunits in calcium channels, potentially through reduced neurotransmitter release.
Highly CitedActivity profile of pregabalin in rodent models of epilepsy and ataxia
Pregabalin shows potential as a treatment for partial seizures in humans, with a different anticonvulsant mechanism than prototype antiepileptic drugs and increased potency and bioavailability.
Non-RCT
Animal StudyHighly CitedFrom basic science to blockbuster drug: the discovery of Lyrica.
Lyrica (pregabalin) is a new blockbuster drug that effectively treats various neuropathic pains, epilepsy, and generalized anxiety disorder by increasing brain GABA levels without inhibiting l-glutamic acid decarboxylase.
Highly CitedPregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.
Pregabalin effectively treats neuropathic pain, partial-onset seizures, and anxiety disorders, with potential for use in generalized anxiety disorder and social anxiety disorder.
Systematic ReviewHighly Cited[Lyrica (pregabalin) in the treatment of focal refractory epilepsy in adults].
Pregabalin is a highly effective and well-tolerated add-on drug for treating focal refractory epilepsy in adults, with favorable pharmacokinetic characteristics and distinct anxyolytic effect.
Case ReportAnalgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins
Gabapentin and pregabalin's analgesic effects may involve interactions with N-methyl-d-aspartate receptors, neurexin-1, and thrombospondins, in addition to voltage-gated calcium channels.
Mechanisms of analgesia by gabapentin and pregabalin – Calcium channel α2-δ [Cavα2-δ] ligands
Gabapentin and pregabalin reduce chronic pain by binding to calcium channel alpha2-delta proteins, not GABAergic, and reducing stimulated transmitter release.
Very Rigorous JournalHighly CitedPregabalin action at a model synapse: Binding to presynaptic calcium channel α2-δ subunit reduces neurotransmission in mice
Pregabalin reduces presynaptic neurotransmitter release without altering postsynaptic receptors or contraction coupling, making it a potential treatment for peripheral neuropathic pain and epilepsy.
Non-RCTAnimal Study