Pregabalin (Lyrica)

Primer

Pregabalin (Trade name: Lyrica) is anticonvulsant and anxiolytic medication used in the treatment of epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, and generalized anxiety disorder.

Pharmacokinetics

Pharmacokinetics of Pregabalin

Absorption Tmax = 1-2 hours
Distribution
Metabolism
Elimination
Half-life 6 hours

Pregabalin: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces
Inhibits

Pharmacodynamics

Mechanism of Action

  • Pregabalin (similar to gabapentin) is a α2δ ligand and binds to the α2δ subunit of voltage-sensitive calcium channels (VSCC).
  • This changes the VSCC conformation to reduce calcium influx and thus reduce excessive stimulation of postsynaptic receptors.

Toxicity

Indications

  • Generalized anxiety disorder[1]

Dosing

Dosing for Pregabalin

Starting 50 mg PO daily
Titration Increase by 50 mg PO q1 week
Maximum 150 to 600 mg range is a therapeutic dose
Taper Gradually taper at least over the course of 1 week, some discontinuation/withdrawal syndromes have been reported.[2]

Formulations

  • Pregabalin comes in oral formulation.

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

Side Effects

  • Pregabalin can also cause myoclonus (especially in the setting of acute kidney injuries when pregabalin is not able to be cleared).[3]

Adverse Events

Clinical Pearls

Special Populations

Geriatric

Pregabalin been studied in the geriatric population for generalized anxiety. Anxiety, somnolence, falls, and infection are potential adverse events to be aware of in the geriatric population.[5]

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Baldwin, D. S., Ajel, K., Masdrakis, V. G., Nowak, M., & Rafiq, R. (2013). Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatric Disease and Treatment.
2) Naveed, S., Faquih, A. E., & Chaudhary, A. M. D. (2018). Pregabalin-associated discontinuation symptoms: a case report. Cureus, 10(10).
3) Desai, A., Kherallah, Y., Szabo, C., & Marawar, R. (2019). Gabapentin or pregabalin induced myoclonus: A case series and literature review. Journal of Clinical Neuroscience, 61, 225-234.
4) Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European neuropsychopharmacology, 27(12), 1185-1215.
5) Montgomery, S., Chatamra, K., Pauer, L., Whalen, E., & Baldinetti, F. (2008). Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. The British journal of psychiatry, 193(5), 389-394.