pregabalin

General Information

Pregabalin is an α2δ calcium-channel ligand (brand Lyrica) approved for several neuropathic pain syndromes, fibromyalgia, and adjunctive therapy for partial-onset seizures (label). While it is approved for generalized anxiety disorder in many countries, U.S. psychiatric use is off label.

In psychiatric practice, pregabalin is typically used as a sedating adjunct for anxiety symptoms and sleep continuity—often when clinicians want an alternative to benzodiazepines or when comorbid pain is prominent.

Compared with gabapentin, pregabalin has more predictable absorption and is often dosed BID, which may contribute to a perception of faster onset. The trade-off is higher rates of dizziness, edema, and weight gain in many cohorts.

Pregabalin has negligible metabolism and is cleared renally; renal function is the key dosing constraint. Declining eGFR can present as oversedation, confusion, and falls.

Pregabalin is Schedule V in the U.S. Misuse/diversion and co-use with opioids/other sedatives increase risk; treat early refills, escalating doses, and intoxication as safety signals and avoid automatic refills.

The pregabalin compare view, pregabalin evidence feed, and pregabalin print page can support aligning anxiety/sleep adjuncts with sedation, edema, and misuse risk.

Pregabalin can be clinically effective for “somatic anxiety” and sleep continuity in some patients, but its controlled-substance status, misuse risk, and metabolic/edema liabilities require explicit safeguards. Treat it as a time-limited adjunct with clear targets and follow-up; avoid escalating doses in response to tolerance without revisiting diagnosis and first-line therapies.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Binds the α2δ subunit of voltage-gated calcium channels, reducing calcium-dependent release of excitatory neurotransmitters; it does not directly bind GABA-A receptors despite the name.

Clinical benefits in anxiety likely reflect reduced physiologic hyperarousal and improved sleep continuity; response should be evaluated alongside daytime functioning and sedation burden.

Because sedation is common, improvement in “anxiety” may reflect tranquilization rather than meaningful cognitive symptom change; pair use with psychotherapy and primary anxiety pharmacotherapy when needed.

• α2δ calcium channel ligand (primary).
• Negligible CYP metabolism; few enzyme-based drug interactions.

Metabolism and Pharmacokinetics

• Negligible metabolism; eliminated renally as unchanged drug (label).
• Mean elimination half-life is ~6.3 hours; dosing is commonly BID (label).
• Clearance is proportional to renal function; dose reductions are required in renal impairment (label).
• Dizziness and somnolence can be early dose-limiting effects; reassess dose appropriateness if symptoms emerge, especially in older adults.

Dosing and Administration

• For off-label anxiety/sleep use, start low and titrate slowly over days to weeks based on sedation, dizziness, and functional impact.
• Avoid rapid escalation or “chasing tolerance,” especially in patients with substance use risk; reassess diagnosis and first-line therapies instead.
• Adjust dosing for renal function and revisit dosing after acute illness or dehydration.
• Taper rather than stopping abruptly after sustained use to reduce rebound anxiety/insomnia and withdrawal-like symptoms.

Monitoring & Labs

• Check renal function (eGFR/CrCl) before starting and after clinical changes that may reduce clearance.
• Monitor sedation, dizziness, and driving/fall risk during titration.
• Track weight and assess peripheral edema; reassess if dyspnea or rapid weight change occurs.
• Screen for misuse/diversion signals (early refills, escalating doses, co-use with opioids/alcohol).
• Taper rather than stopping abruptly after sustained use.

Sources: FDA/DailyMed label; generalized anxiety disorder reviews/meta-analysis; misuse/diversion systematic review update.

Adverse Effects

Interactions

• Additive sedation/respiratory depression with opioids, benzodiazepines, alcohol, and other CNS depressants.
• Few CYP interactions because pregabalin has negligible metabolism; focus medication reconciliation on sedation burden, renal function, and controlled-substance risk.

Other Useful Information

• If pregabalin is used for insomnia symptoms, define the target (sleep onset vs sleep maintenance) and reassess within weeks; avoid indefinite nightly use without a plan.
• In serious mental illness, sedation can worsen negative symptoms and functional impairment; consider non-sedating anxiety strategies when daytime function is a priority.
• Use controlled-substance safeguards (limited quantities, no automatic refills, documentation of co-prescribed sedatives and substance use risk).

References

1. Pregabalin prescribing information (Lyrica) — DailyMed (2025)
2. Gabapentin and Pregabalin for the Treatment of Anxiety Disorders — Clinical Pharmacology in Drug Development (2018)
3. A Meta Analysis OF THE Efficacy OF Pregabalin IN THE Treatment OF Generalized Anxiety Disorder — The Canadian Journal of Psychiatry (2011)
4. Pregabalin for generalized anxiety disorder — International Clinical Psychopharmacology (2017)
5. Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update — Drugs (2021)