Why is gabapentin (Neurontin) considered a controlled substance, particularly in patients with a history of substance abuse?

Why Gabapentin is Classified as a Controlled Substance

Gabapentin has been designated as a controlled substance in several jurisdictions due to documented evidence of abuse potential, dependence, and withdrawal symptoms, particularly among individuals with a history of substance use disorders, and because it significantly increases respiratory depression risk and opioid-related mortality when combined with opioids. 1, 2

Primary Reasons for Controlled Status

Abuse and Dependence Potential

• Gabapentinoids produce reinforcing euphoria, sedation, and dissociation, which were recognized early in their clinical use, though initially believed to carry low addiction risk 1
• Approximately 50% of patients prescribed gabapentinoids were treated continuously for at least 12 months, with sudden cessation leading to physical and psychological withdrawal symptoms 1
• Individuals with psychiatric disorders or substance use disorder are at high risk for gabapentin misuse and abuse 3
• Patients with opioid use disorders demonstrate particularly elevated risk of abusing gabapentinoids 3, 4

Dangerous Drug Interactions

• When gabapentinoids are taken with opioids, dangerous respiratory depression can occur, significantly increasing overdose risk 1
• Gabapentin is commonly abused to potentiate opioid effects, creating synergistic respiratory depression similar to benzodiazepine-opioid combinations 2
• A total of 86 fatalities associated with gabapentin, mostly in combination with opioids, were identified in European surveillance data 5

Documented Misuse Patterns

• All documented cases of gabapentin addiction occurred in patients with previous history of alcohol, cocaine, or opioid abuse 4
• Patients typically took more than 3000 mg/day (range 600-8000 mg/day) when abusing gabapentin 4
• Misuse rates of 1.1% in the general population and 22% in drug abuse treatment centers have been reported 4
• Reporting frequency of gabapentinoid misuse/abuse/dependence has increased over time, with 7,639 pregabalin and 4,301 gabapentin adverse drug reaction reports in European databases 5

Withdrawal Syndrome Characteristics

• Withdrawal occurs within 12 hours to 7 days of discontinuation 4
• Physical and psychological withdrawal symptoms can be severe, necessitating careful tapering and support for patients on long-term therapy 1
• Long-term prescribing (>12 months) is common but often not recommended by clinical guidelines or of doubtful efficacy 2

Clinical Implications for Prescribers

Risk Assessment Requirements

• Prescribers must carefully evaluate patients for history of drug abuse before prescribing gabapentin, though this is not an absolute contraindication 2
• A history of substance use disorder is a significant risk factor that requires enhanced monitoring 3, 6
• Validated risk assessment tools should be used to stratify risk when prescribing controlled substances 7

Monitoring Obligations

• Signs of misuse and abuse should be monitored, including dose escalation, early refill requests, and seeking prescriptions from multiple providers 3, 7
• Prescription drug monitoring program (PDMP) review is necessary to check for concurrent controlled substance prescriptions and patterns of doctor shopping 7

Jurisdictional Variations

• Gabapentin is not a federally scheduled drug in the United States, differing from opioids and benzodiazepines which have federal controlled substance designations 2
• Several countries and U.S. states have classified gabapentinoids as controlled substances in response to abuse potential 6
• Prescribers must confirm with their respective state licensure authorities regarding local laws and regulations, as gabapentin's legal status varies significantly by jurisdiction 2

Common Pitfalls to Avoid

• Do not assume gabapentin is "safe" simply because it lacks federal scheduling - the evidence clearly demonstrates abuse potential in vulnerable populations 3, 6
• Avoid prescribing to patients with active substance use disorders when possible, and if prescribed, implement frequent monitoring 3
• Never abruptly discontinue gabapentin in patients on long-term therapy - taper slowly to prevent withdrawal symptoms 1
• Be vigilant about concurrent opioid prescriptions due to synergistic respiratory depression risk 1, 2