Is there a trend of pregabalin (Lyrica) abuse and misuse among patients?

From the Guidelines

There is a concerning trend of pregabalin (Lyrica) abuse and misuse among patients, particularly among those with a history of substance use disorders, psychiatric comorbidities, and younger age. Pregabalin has demonstrated potential for abuse, particularly when taken at higher-than-prescribed doses, which can produce euphoric effects, relaxation, and sedation 1. The abuse potential appears dose-dependent, with higher doses (300mg or more) more likely to produce desirable euphoric effects. Risk factors for pregabalin abuse include prior opioid or benzodiazepine use disorders, psychiatric comorbidities, and younger age 1.

Key Considerations

• Pregabalin's pharmacological mechanism, which involves action on voltage-gated calcium channels, indirectly affects GABA neurotransmission and dopamine release in the brain's reward pathways, similar to other substances with abuse potential 1.
• Healthcare providers should exercise caution when prescribing pregabalin, particularly to patients with substance use histories, by implementing regular monitoring, prescribing limited quantities, considering lower starting doses, and educating patients about proper use 1.
• Tools such as agreements, urine drug testing, and use of drug monitoring programs may mitigate risk, although more information is needed to determine which are most effective in preventing pregabalin abuse and misuse 1.

Recommendations for Healthcare Providers

• Implement regular monitoring and prescribing limited quantities of pregabalin to minimize the risk of abuse and misuse.
• Consider lower starting doses and educate patients about proper use to reduce the potential for euphoric effects and dependence.
• Use validated risk-assessment instruments and screening questionnaires to identify patients prone to misuse or those currently misusing prescribed medications, such as the Screener and Opioid Assessment for Patients in Pain, the Opioid Risk Tool, and its revision, the Current Opioid Misuse Measure, and the Brief Risk Interview and Questionnaire 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) In controlled clinical studies in over 5500 patients, 4% of pregabalin-treated patients and 1% of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%.
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. In the postmarketing experience, in addition to these reported symptoms there have also been reported cases of anxiety and hyperhidrosis.

Trend of Abuse and Misuse: There is evidence suggesting a potential for pregabalin abuse and misuse among patients.

• Abuse: Pregabalin has been associated with subjective ratings of "good drug effect," "high," and "liking" similar to diazepam in recreational users.
• Misuse: 4% of pregabalin-treated patients reported euphoria as an adverse reaction, with higher rates in some patient populations.
• Dependence: Symptoms consistent with physical dependence have been reported following abrupt or rapid discontinuation of pregabalin, including insomnia, nausea, headache, diarrhea, anxiety, and hyperhidrosis 2.

From the Research

Pregabalin Abuse and Misuse Trend

• There is a growing concern about the abuse and misuse of pregabalin, with increasing reports of patients self-administering higher than recommended doses to achieve euphoric highs 3, 4, 5.
• Studies have shown that pregabalin possesses modulatory effects on the GABA and glutamate systems, leaving room for an abuse potential 4.
• The majority of case reports concerning abuse of pregabalin involved patients with a history of substance abuse, and epidemiological studies found evidence of abuse, especially among opiate abusers 3, 4, 5.
• Pregabalin is characterized by higher potency, quicker absorption rates, and greater bioavailability levels than gabapentin, which may contribute to its misuse liability 6, 5.

Risk Factors and Consequences

• Risk factors for pregabalin abuse include a history of substance abuse, particularly opioids, and psychiatric co-morbidities 3, 6, 4.
• The consequences of pregabalin misuse can be severe, including withdrawal symptoms, overdose, and increased risk of opioid-related morbidity and mortality when used concomitantly 3, 6, 7.
• Prescribers should be aware of high-risk populations and monitor for signs of abuse, especially in patients with a history of substance abuse 3, 4, 5.

Regulatory and Clinical Implications

• Several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug-monitoring programs 6.
• Harm reduction efforts and increased patient and provider education are necessary to mitigate the concerning gabapentinoid misuse trend 6, 7.
• Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate a possible previous history of drug abuse and provide possible assistance in tapering off the medication 5, 7.