Why is Lyrica (pregabalin) considered a controlled substance?

Why Lyrica (Pregabalin) is a Controlled Substance

Pregabalin is classified as a Schedule V controlled substance by the FDA because it produces euphoria, "high," and "liking" effects similar to diazepam in recreational drug users, and has demonstrated potential for abuse, physical dependence, and withdrawal symptoms upon discontinuation. 1

Evidence of Abuse Potential

The FDA drug label provides the primary regulatory justification for controlled substance classification:

• In recreational drug users (N=15), a single 450 mg dose of pregabalin produced subjective ratings of "good drug effect," "high," and "liking" comparable to 30 mg of diazepam 1
• In clinical trials with over 5,500 patients, 4% of pregabalin-treated patients reported euphoria as an adverse reaction (compared to 1% on placebo), with rates ranging from 1-12% in certain patient populations 1

Physical Dependence and Withdrawal

Pregabalin meets criteria for physical dependence:

• Abrupt discontinuation produces withdrawal symptoms including insomnia, nausea, headache, diarrhea, anxiety, and hyperhidrosis 1
• Approximately 50% of patients prescribed gabapentinoids (including pregabalin) were treated continuously for at least 12 months, and sudden cessation can lead to both physical and psychological withdrawal 2
• The FDA explicitly warns that pregabalin should be tapered gradually over a minimum of 1 week when discontinuing to avoid withdrawal symptoms 3

Real-World Abuse Patterns

Clinical evidence demonstrates actual abuse in vulnerable populations:

• Among opiate-dependent patients undergoing replacement therapy, 12.1% tested positive for pregabalin without any medical indication for its use 4
• Case reports document patients with opioid-seeking behavior obtaining pregabalin from multiple sources, with one patient receiving 88,500 mg over 28 days 5
• Pregabalin is commonly abused to potentiate opioid effects, and when combined with opioids, significantly increases respiratory depression risk and opioid-related mortality 6

Neurobiological Mechanisms of Abuse

Research demonstrates pregabalin affects brain reward pathways similarly to other drugs of abuse:

• Pregabalin (90 mg/kg) produces conditioned place preference in animal models, indicating reinforcing effects that suggest abuse liability 7
• Like heroin and cocaine, pregabalin alters glutamate homeostasis by reducing expression of glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter (xCT) in the nucleus accumbens and medial prefrontal cortex 7

Clinical Context and Prescribing Implications

Despite Schedule V classification (lowest abuse potential among controlled substances):

• The FDA mandates careful evaluation of patients for history of drug abuse and observation for signs of pregabalin misuse or abuse, including tolerance development, dose escalation, and drug-seeking behavior 1
• Prescribers must be particularly vigilant when treating patients with past or current opiate dependency, as this population shows significantly higher rates of pregabalin abuse 4
• When combined with opioids, benzodiazepines, or other CNS depressants, pregabalin can cause serious breathing problems 3

Comparison to Related Medications

The controlled substance status distinguishes pregabalin from its structural analog:

• Gabapentin is not federally scheduled as a controlled substance, though some states have implemented their own restrictions 6
• Both medications share similar abuse potential profiles, particularly among individuals with poly-substance abuse history 6
• Tramadol was similarly reclassified as a Schedule IV controlled substance in 2014 by the FDA based on abuse and dependence potential 2