Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic, and anxiolytic amino acid medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless legs syndrome, opioid withdrawal, and generalized anxiety disorder (GAD).

[13] Common side effects can include headache, dizziness, sleepiness, confusion, trouble with memory, poor coordination, dry mouth, problems with vision, and weight gain.

[46][47] Pregabalin has potential for recreational use and abuse; it has a wide therapeutic index and margin of safety compared with other CNS depressants, alongside its ability to induce euphoria, anxiolysis, and sedation.

[66][67] However, there is concern regarding pregabalin's off-label use due to the lack of strong scientific evidence for its efficacy in multiple conditions and its proven side effects.

[79] Exposure to pregabalin is associated with weight gain, drowsiness, fatigue, dizziness, vertigo, leg swelling, disturbed vision, loss of coordination, and euphoria.

The FDA determined that the substance dependence profile of pregabalin, as measured by a personal physical withdrawal checklist, was quantitatively less than benzodiazepines.

[89] In December 2019, the US Food and Drug Administration (FDA) warned about serious breathing issues for those taking gabapentin or pregabalin when used with central nervous system (CNS) depressants or for those with lung problems.

[90] Among 49 case reports submitted to the FDA over the five-year period from 2012 to 2017, twelve people died from respiratory depression with gabapentinoids, all of whom had at least one risk factor.

Several people with kidney failure developed myoclonus while receiving pregabalin, apparently as a result of the gradual accumulation of the drug.

Plasma, serum, or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized people.

The manufacturer notes some potential pharmacological interactions with opioids, benzodiazepines, barbiturates, ethanol (alcohol), and other drugs that depress the central nervous system.

[97] Pregabalin is a gabapentinoid medication, meaning drugs that chemically are derivatives of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter.

These excitatory neurotransmitters include glutamate, norepinephrine (noradrenaline), serotonin, dopamine, substance P, and calcitonin gene-related peptide.

[101][103] In accordance, inhibition of α2δ-1 proteins by pregabalin appears to be responsible for its anticonvulsant, analgesic, and anxiolytic effects in animal models.

[27][104] In accordance, while gabapentinoids like pregabalin and gabapentin have nanomolar affinities for the α2δ subunit, their potencies in vivo are in the low micromolar range, and competition for binding by endogenous L-amino acids has been said to likely be responsible for this discrepancy.

[30] The LAT1 is easily saturable, so the pharmacokinetics of gabapentin are dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.

[12] Pregabalin is rapidly absorbed when administered on an empty stomach, with a Tmax (time to peak levels) of generally less than or equal to 1 hour at doses of 300 mg or less.

[116][117][118] Pregabalin also closely resembles the α-amino acids L-leucine and L-isoleucine, and this may be of greater relevance in relation to its pharmacodynamics than its structural similarity to GABA.

The US received FDA approval for use in treating epilepsy, diabetic neuropathic pain, and postherpetic neuralgia in December 2004.

[125] In 2017, the FDA approved pregabalin extended-release Lyrica CR for the management of neuropathic pain associated with diabetic peripheral neuropathy, and postherpetic neuralgia.

[126] However, unlike the immediate release formulation, Lyrica CR was not approved for the management of fibromyalgia or as add-on therapy for adults with partial onset seizures.

[127][9] In the United States, the FDA has approved pregabalin for adjunctive therapy for adults with partial onset seizures, management of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy, and the treatment of fibromyalgia.

[137] Pregabalin has also been approved in the European Union, the United Kingdom, and Russia for treatment of generalized anxiety disorder.

[140] From 2008 until 2018, Pfizer engaged in extensive direct-to-consumer advertising campaigns to promote its branded product Lyrica for fibromyalgia and diabetic nerve pain indications.

In January 2016, the company spent a record amount, $24.6 million for a single drug on TV ads, reaching global revenues of $14 billion, more than half in the United States.

For Lyrica and three other drugs, Pfizer was fined a record amount of US$2.3 billion by the Department of Justice,[142][143][144] after pleading guilty to advertising and branding "with the intent to defraud or mislead".

Pfizer illegally promoted the drugs, with doctors "invited to consultant meetings, many in resort locations; attendees expenses were paid; they received a fee just for being there", according to prosecutor Michael Loucks.

From October 2015, GPs were forced to change people from generic pregabalin to branded until the second patent ran out in July 2017.

[149] As of October 2017, pregabalin is marketed under many brand names: Algerika, Alivax, Alyse, Alzain, Andogablin, Aprion, Averopreg, Axual, Balifibro, Brieka, Clasica, Convugabalin, Dapapalin, Dismedox, Dolgenal, Dolica, Dragonor, Ecubalin, Epica, Epiron, Gaba-P, Gabanext, Gabarol, Gabica, Gablin, Gablovac, Gabrika, Gavin, Gialtyn, Glonervya, Helimon, Hexgabalin, Irenypathic, Kabian, Kemirica, Kineptia, Lecaent, Lingabat, Linprel, Lyribastad, Lyric, Lyrica, Lyrineur, Lyrolin, Lyzalon, Martesia, Maxgalin, Mystika, Neuragabalin, Neugaba, Neurega, Neurica, Neuristan, Neurolin, Neurovan, Neurum, Newrica, Nuramed, Paden, Pagadin, Pagamax, Painica, Pevesca, PG, Plenica, Pragiola, Prebalin, Prebanal, Prebel, Prebictal, Prebien, Prefaxil, Pregaba, Pregabalin, Pregabalina, Pregabaline, Prégabaline, Pregabalinum, Pregabateg, Pregaben, Pregabid, Pregabin, Pregacent, Pregadel, Pregagamma, Pregalex, Pregalin, Pregalodos, Pregamid, Pregan, Preganerve, Pregastar, Pregatrend, Pregavalex, Pregdin Apex, Pregeb, Pregobin, Prejunate, Prelin, Preludyo, Prelyx, Premilin, Preneurolin, Prestat, Pretor, Priga, Provelyn, Regapen, Resenz, Rewisca, Serigabtin, Symra, Vronogabic, Xablin, and Xil.

[150] It is marketed as a combination drug with mecobalamin under the brand names Agemax-P, Alphamix-PG, Freenerve-P, Gaben, Macraberin-P, Mecoblend-P, Mecozen-PG, Meex-PG, Methylnuron-P, Nervolin, Nervopreg, Neurica-M, Neuroprime-PG, Neutron-OD, Nuroday-P, Nurodon-PG, Nuwin-P, Pecomin-PG, Prebel-M, Predic-GM, Pregacent-M, Pregamet, Preganerv-M, Pregeb-M OD, Pregmic, Prejunate Plus, Preneurolin Plus, Pretek-GM, Rejusite, Renerve-P, Safyvit-PR, Vitcobin-P, and Voltanerv with Methylcobalamin and ALA by Cogentrix Pharma.