Is pregabalin less addictive than benzodiazepines?

Pregabalin is NOT Less Addictive Than Benzodiazepines

Contrary to initial beliefs, pregabalin carries significant addiction and dependence risks that are comparable to benzodiazepines, and both medications require careful monitoring for abuse potential. While pregabalin was initially marketed as having lower addiction risk, accumulating evidence demonstrates substantial abuse liability, particularly in vulnerable populations.

Evidence from Guidelines and Drug Labels

The 2019 Public Health England review published in The Lancet Psychiatry definitively states that gabapentinoids (including pregabalin) were "initially believed to carry a relatively low risk of dependence and withdrawal symptoms" but this assumption has been proven incorrect 1. The guideline explicitly notes that pregabalin causes "reinforcing euphoria, sedation, and dissociation" from early use 1.

The FDA drug label for pregabalin (Schedule V controlled substance) reveals critical addiction data 2:

• In recreational drug users, pregabalin 450mg produced subjective ratings of "good drug effect," "high," and "liking" similar to diazepam 30mg
• In clinical trials, 4% of pregabalin patients reported euphoria (vs 1% placebo), with rates reaching 1-12% in certain populations
• Physical dependence symptoms occur upon discontinuation, including insomnia, nausea, headache, diarrhea, anxiety, and hyperhidrosis

Comparative Addiction Risk

Direct Comparison Data

The most rigorous systematic review on this topic 3 (2017) found:

• Pregabalin is "somewhat more addictive than gabapentin" regarding behavioral dependence symptoms
• The principal at-risk population consists of patients with current or past substance use disorders, who preferred pregabalin over gabapentin
• Pure pregabalin overdoses can be lethal, especially when mixed with opioids and sedatives

A 2009 assessment concluded that "pregabalin is likely to have a lower potential for abuse than benzodiazepines" based on weaker positive psychological effects 4. However, this older evidence conflicts with more recent data.

Critical Safety Concerns

The 2021 analysis 5 provides alarming mortality data:

• 244 deaths from pregabalin poisoning recorded in 2019 in England
• Death rates involving pregabalin have been rising steeply for 10 years
• Pregabalin deaths now exceed those from diazepam, fentanyl, tricyclics, or SSRIs as groups
• Most poisonings involve concomitant opioid or other drug use

Clinical Implications

Who Is at Highest Risk

Avoid pregabalin entirely in patients with:

• Current or past substance use disorders (especially opioid and multi-drug users) 3
• History of recreational sedative/hypnotic use 2
• Concurrent opioid or benzodiazepine prescriptions 1, 6

Withdrawal and Dependence

Both medications produce physical dependence 1:

• Approximately 50% of patients on either pregabalin or benzodiazepines receive continuous prescriptions for ≥12 months 1
• Abrupt discontinuation of either medication causes withdrawal symptoms
• Cross-tapering pregabalin with short-term diazepam has been used to manage pregabalin withdrawal 7

Prescribing Cautions

The 2019 guideline emphasizes 1:

• Long-term prescribing of pregabalin is "either not recommended by clinical guidelines or of doubtful efficacy in many cases"
• When gabapentinoids are taken with opioids, dangerous respiratory depression can occur
• Pregabalin was reclassified as a Class C controlled drug in the UK in 2019 due to addiction risks 5

Common Pitfalls to Avoid

1. Do not assume pregabalin is "safer" than benzodiazepines - mortality data contradicts this assumption 5
2. Do not prescribe pregabalin to patients already on opioids without extreme caution - synergistic respiratory depression is life-threatening 1
3. Do not rely on short-term trial data showing marginal efficacy differences from placebo while ignoring long-term tolerance, dependence, and withdrawal 5
4. Monitor for dose escalation and drug-seeking behavior in all patients 2
5. Be cautious with doses above 450mg/day due to cognitive effects 8

Bottom Line

The claim that pregabalin is less addictive than benzodiazepines is not supported by the highest quality, most recent evidence. Both carry substantial addiction risk, require careful patient selection, and mandate monitoring for abuse. The rising mortality associated with pregabalin, particularly when combined with opioids, suggests it may pose equal or greater real-world harm than benzodiazepines in certain contexts 5. Prescribe either medication with extreme caution, avoid both in patients with substance use history, and never combine with opioids.