Pregabalin Vs Gabapentin Why Is Pregabalin Controlled

Pregabalin and gabapentin are both medications primarily used to treat neuropathic pain, epilepsy, and certain anxiety disorders. While they share similar mechanisms of action and therapeutic uses, a critical distinction lies in their legal classification: pregabalin is a controlled substance in many countries, including the United States and the United Kingdom, while gabapentin remains uncontrolled or less strictly regulated. Understanding why this difference exists requires examining pharmacology, abuse potential, clinical outcomes, and real-world patterns of misuse.

How Pregabalin and Gabapentin Work

Both drugs modulate calcium channels in the central nervous system by binding to the α2-δ subunit of voltage-gated calcium channels. This action reduces the release of excitatory neurotransmitters such as glutamate, noradrenaline, and substance P, which play roles in pain signaling and seizure activity.

Despite this shared mechanism, pregabalin has a significantly higher affinity for the target site—approximately six times greater than gabapentin. This translates into more predictable absorption, faster onset of action, and greater potency at lower doses. Unlike gabapentin, whose absorption becomes saturated at higher doses (leading to variable bioavailability), pregabalin is almost completely absorbed regardless of dose, making its effects more consistent across patients.

Tip: Because pregabalin has linear pharmacokinetics, dose adjustments are more straightforward compared to gabapentin, which often requires careful titration due to nonlinear absorption.

Therapeutic Uses and Efficacy Comparison

Both medications are FDA-approved for specific indications, though their approved uses differ slightly:

Condition	Pregabalin Approved	Gabapentin Approved
Neuropathic Pain (e.g., diabetic neuropathy)	Yes	Yes
Fibromyalgia	Yes	No
Postherpetic Neuralgia	Yes	Yes
Epilepsy (adjunctive therapy)	Yes	Yes
Generalized Anxiety Disorder (GAD)	Yes (in EU/UK)	No
Restless Legs Syndrome	No	Off-label use common

Clinical studies suggest that pregabalin may offer superior efficacy in conditions like fibromyalgia and generalized anxiety disorder. Its ability to produce noticeable symptom relief within days—compared to weeks with some other treatments—has contributed to its widespread adoption. However, this rapid effect also increases its appeal beyond legitimate medical use.

Why Is Pregabalin Controlled?

The primary reason pregabalin is classified as a controlled substance (Schedule V under the U.S. Controlled Substances Act since 2015, and Class C in the UK under the Misuse of Drugs Act) is its documented potential for abuse and dependence.

While originally believed to have low misuse liability, growing evidence from emergency departments, addiction clinics, and forensic data revealed increasing cases of recreational use. Users report euphoric effects, particularly when pregabalin is taken in high doses or combined with opioids or benzodiazepines. These combinations can enhance sedation and respiratory depression, significantly increasing overdose risk.

“Pregabalin’s reinforcing effects and synergy with opioids make it a dangerous tool for misuse, especially in populations already vulnerable to substance use disorders.” — Dr. Laura Chen, Addiction Medicine Specialist

In contrast, gabapentin has historically shown lower rates of recreational use. Although it can be misused, especially in individuals with opioid use disorder, its pharmacokinetic profile—lower potency, slower onset, and ceiling effect due to saturable absorption—limits its abuse potential. As a result, gabapentin remains unscheduled federally in the U.S., though several states have implemented monitoring programs.

Abuse Patterns and Public Health Impact

A mini case study from rural Ohio illustrates the shift in prescribing trends and unintended consequences:

In 2018, a local clinic began transitioning chronic pain patients from opioids to pregabalin amid tightening opioid regulations. Within two years, emergency room visits related to pregabalin intoxication rose by 73%. Many patients obtained prescriptions through multiple providers, while others acquired the drug illicitly. Some combined it with heroin, citing enhanced \"high\" and reduced withdrawal symptoms. This prompted county health officials to advocate for prescription drug monitoring program (PDMP) inclusion for pregabalin—an effort later adopted statewide.

This scenario reflects broader national trends. The CDC reported a steady increase in pregabalin-involved overdose deaths between 2012 and 2020, often in combination with fentanyl or methadone. These findings were instrumental in reclassifying pregabalin as a controlled substance.

Safety, Dependence, and Withdrawal Risks

Another factor contributing to pregabalin’s controlled status is the severity of discontinuation symptoms. Abrupt cessation after prolonged use can lead to:

• Anxiety and insomnia
• Nausea and headaches
• Tachycardia and hypertension
• Seizures (in susceptible individuals)

These withdrawal effects are more pronounced than those associated with gabapentin, necessitating gradual tapering. The risk of physiological dependence—even at therapeutic doses—adds to regulatory concerns.

Prescribing Considerations Checklist

For healthcare providers, managing these medications responsibly involves vigilance and structured protocols:

1. Review patient history for substance use disorders before initiating treatment.
2. Use state PDMP databases to screen for concurrent controlled substance prescriptions.
3. Start at the lowest effective dose and titrate slowly.
4. Avoid combining with CNS depressants unless absolutely necessary.
5. Discuss risks of dependence and safe discontinuation during informed consent.
6. Schedule regular follow-ups to assess efficacy and signs of misuse.
7. Document rationale for long-term use, especially for off-label indications.

Regulatory Differences: A Global Perspective

Regulation varies internationally:

• United States: Pregabalin is Schedule V; gabapentin is not federally scheduled but monitored in 14+ states.
• United Kingdom: Pregabalin became Class C in 2017; gabapentin was rescheduled to Class C in 2019 due to rising misuse.
• Canada: Pregabalin is a controlled substance under Schedule IV; gabapentin is not scheduled but tracked in some provinces.
• Australia: Both are prescription-only, but neither is currently scheduled under the Poisons Standard for abuse potential.

This evolving landscape shows that gabapentin may face tighter restrictions in the future as surveillance data accumulates.

Frequently Asked Questions

Can you get addicted to gabapentin?

Yes, though less commonly than with pregabalin. Individuals with a history of substance abuse are at higher risk. Symptoms of dependence include cravings, inability to cut down, and withdrawal upon stopping.

Why isn’t gabapentin controlled if it’s similar to pregabalin?

Gabapentin has lower potency, slower brain penetration, and limited euphoric effects. While misuse occurs, population-level harm remains lower. However, several U.S. states now require electronic prescriptions or monitor its use via PDMPs.

Is it safe to switch from pregabalin to gabapentin?

Switching is possible but must be done gradually under medical supervision. Due to differences in dosing and bioavailability, direct conversion isn't equivalent. For example, 150 mg of pregabalin does not equal 150 mg of gabapentin—the latter typically requires higher total daily doses.

Conclusion: Balancing Benefit and Risk

Pregabalin offers significant advantages over gabapentin in terms of potency, consistency, and speed of action. However, these same qualities contribute to its higher potential for misuse, dependence, and severe withdrawal—key reasons behind its classification as a controlled substance. Gabapentin, while safer in terms of abuse liability, is not without risks, especially in polypharmacy scenarios.

As clinicians and patients navigate pain and neurological management in an era of heightened awareness around medication safety, understanding the nuances between these two drugs is essential. Prescribing should be guided by individual risk assessment, ongoing monitoring, and clear communication about benefits and dangers.

🚀 Take action today: If you're prescribing or taking either medication, review current guidelines, check your state's PDMP policies, and discuss long-term plans with your care provider to ensure safe, effective treatment.