Is pregabalin (lyrica) addictive?

From the Guidelines

Pregabalin has the potential to be addictive, particularly in individuals with a history of substance abuse, due to its risk of physical and psychological dependence. According to the study published in the Annual Review of Medicine 1, pregabalin, an anticonvulsant, is believed to exert analgesic effects by binding to calcium channels in the brain and spinal cord, which can lead to calming and sometimes euphoric effects. This can result in misuse, especially in people prone to substance abuse. Key points to consider include:

• Tolerance can develop with regular use, requiring higher doses over time to achieve the same effect
• Physical dependence can occur even when taken as prescribed, leading to withdrawal symptoms if stopped abruptly, such as insomnia, headaches, nausea, anxiety, and in severe cases, seizures
• Pregabalin is classified as a controlled substance (Schedule V in the US) due to its potential for abuse and dependence
• The study highlights the importance of using pregabalin and other nonopioid analgesics judiciously, given their potential side effects and limitations, including partial efficacy and slower onset of action compared to opioids. It is essential for patients prescribed pregabalin to take it exactly as directed, never increase the dose without medical supervision, and work with their healthcare provider on a gradual tapering schedule when discontinuing the medication to minimize the risk of addiction and withdrawal symptoms 1.

From the FDA Drug Label

1. Drug Abuse and Dpendence 9.1 Controlled Substance Pregabalin is a Schedule V controlled substance. Pregabalin is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
2. 2 Abuse In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, pregabalin (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose)
3. 3 Dependence In clinical studies, following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see WARNINGS AND PRECAUTIONS (5.6)], consistent with physical dependence.

Pregabalin has the potential for abuse and dependence. The drug label reports that pregabalin is a Schedule V controlled substance and that patients should be evaluated for a history of drug abuse and observed for signs of misuse or abuse. Additionally, the label notes that some patients have reported symptoms consistent with physical dependence after abrupt or rapid discontinuation of pregabalin, such as insomnia, nausea, and headache 2. Key signs of potential abuse or dependence include:

• Development of tolerance
• Dose escalation
• Drug-seeking behavior
• Euphoria as an adverse reaction, reported by 4% of pregabalin-treated patients in clinical studies.

From the Research

Pregabalin Addiction

• Pregabalin has been linked to addictive behaviors, with case reports and studies suggesting its potential to cause abuse and dependence 3, 4, 5.
• The majority of cases involving pregabalin abuse or dependence have been reported in patients with a history of substance abuse or psychiatric disorders 4, 5.
• Risk factors for pregabalin addiction may include male sex, psychiatric history, and history of opioid addiction 4.
• Pregabalin has been shown to produce euphoric effects, particularly when taken in high doses or via alternative routes of administration 5.
• While some studies suggest that pregabalin has a low potential for addiction in the general population, it may be more likely to be misused in patients with a history of substance use disorders 6.

Clinical Implications

• Prescribers should be cautious when administering pregabalin to patients with a history of substance abuse or psychiatric disorders 3, 7.
• Monitoring for signs of abuse, such as increased dosage or frequency of use, is essential in patients taking pregabalin 5.
• Pregabalin's potential for abuse and dependence should be weighed against its therapeutic benefits when considering its use in clinical practice 7.

Mechanism of Action

• Pregabalin's modulatory effects on the GABA and glutamate systems may contribute to its potential for abuse 5.
• The drug's binding to the α²-δ subunit protein of voltage-gated calcium channels may also play a role in its addictive properties 7.