Why is Lyrica (pregabalin) a controlled substance, but Neurontin (gabapentin) is not?

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From the Guidelines

Lyrica (pregabalin) is classified as a controlled substance due to its higher abuse potential compared to Neurontin (gabapentin), which is not controlled, primarily because of differences in their pharmacological properties and abuse potentials, as noted in studies such as 1 that highlight medicines associated with dependence or withdrawal. The main reason for this classification difference lies in how each drug interacts with the body and its potential for misuse. Lyrica is absorbed more quickly and reaches the brain faster, producing more pronounced euphoric effects, which contributes to its higher abuse potential. In contrast, Neurontin, while used for similar conditions like neuropathic pain and seizures, has historically shown a lower potential for abuse. However, recent increases in gabapentin abuse have led some states to monitor its use more closely, despite its non-controlled status at the federal level. Key factors influencing the controlled substance status of Lyrica include its potent binding to calcium channels in the nervous system, its rapid absorption, and its potential to cause dependence, as discussed in the context of managing neuropathic pain 1. The pharmacological management of neuropathic pain, as outlined in guidelines such as those found in 1, recommends careful consideration of the potential for dependence and abuse when prescribing medications like Lyrica and Neurontin. Given the potential for abuse and dependence associated with these medications, particularly Lyrica, it is crucial for healthcare providers to closely monitor patients prescribed these drugs and to follow guidelines that minimize the risk of misuse, such as those suggested in studies like 1 and 1.

From the FDA Drug Label

  1. Drug Abuse and Dpendence 9.1 Controlled Substance Pregabalin is a Schedule V controlled substance. 9.1 Controlled Substance Gabapentin is not a scheduled drug.
  • Pregabalin is a controlled substance because it is classified as a Schedule V controlled substance, as stated in its drug label 2.
  • Gabapentin is not a controlled substance, as it is not scheduled and does not exhibit affinity for receptor sites associated with drugs of abuse, according to its drug label 3. The reason for this difference is not explicitly stated in the provided drug labels, but it may be related to the potential for misuse or abuse and the drug's pharmacological properties.

From the Research

Comparison of Lyrica and Neurontin

  • Lyrica (pregabalin) is categorized as a Schedule V drug in the US Drug Enforcement Administration's Controlled Substances Act, indicating a low potential for abuse 4.
  • Neurontin (gabapentin) is not controlled in the same way, despite both being gabapentinoids with similar mechanisms of action.
  • Studies have shown that pregabalin has a higher potential for abuse than gabapentin, particularly in patients with a history of substance use disorders 5, 6.

Abuse Potential

  • Pregabalin has been reported to cause euphoric and dissociative effects when taken in high doses or used via alternative routes of administration, such as nasal insufflation or venous injection 6.
  • Gabapentinoids, including pregabalin, have been found to have limited rewarding properties and marginal notes on relapses, suggesting a lower potential for addiction 5.
  • However, patients with a history of substance abuse are at higher risk of developing an addiction to gabapentinoids, particularly pregabalin 5, 6.

Clinical Use

  • Pregabalin is recommended as a second-line treatment for neuropathic pain, while gabapentin is recommended as a first-line treatment 7.
  • Both pregabalin and gabapentin are used to treat various conditions, including epilepsy, anxiety disorders, and fibromyalgia.
  • The choice between pregabalin and gabapentin depends on the specific condition being treated, as well as the patient's medical history and potential risk factors for addiction 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Potential for pregabalin abuse or diversion after past drug-seeking behavior.

The Journal of the American Osteopathic Association, 2010

Research

How addictive are gabapentin and pregabalin? A systematic review.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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