Pregabalin

From PsychonautWiki
(Redirected from Lyrica)
Jump to: navigation, search
Summary sheet: Pregabalin
Pregabalin
Molecular structure of pregabalin
Pregabalin.svg
Chemical Nomenclature
Common names Pregabalin, Lyrica, Nervalin
Substitutive name 3-Isobutyl GABA
Systematic name (S)-3-(Aminomethyl)-5-methylhexanoic acid
Class Membership
Psychoactive class Depressant
Chemical class Gabapentinoid
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Bioavailability 90%[citation needed]
Threshold 50 - 150 mg
Light 150 - 300 mg
Common 300 - 600 mg
Strong 600 - 900 mg
Heavy 900 mg +
Duration
Total 6 - 14 hours
Onset 30 - 90 minutes









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Pregabalin (also known as β-isobutyl-γ-aminobutyric acid, 3-isobutyl GABA, and by the trade-name Lyrica) is a synthetic depressant drug of the gabapentinoid chemical class.

Pregabalin is a common prescription drug, which is typically used to treat neuropathic pain, anxiety, restless leg syndrome, and as an adjunct drug in the treatment of seizures.[citation needed]

This compound has a pharmacologically comparable to that of gabapentin as they both share similar mechanisms of action and induce similar subjective effects. The advantages pregabalin has over gabapentin include greater bioavailability and potency.[citation needed]

Chemistry

Pregabalin is a structural analog of GABA (gamma-aminobutyric acid), with an isobutyl group substituted on the beta carbon of the aminobutyric chain. Pregabalin is similar in structure to other gabapentinoids, such as gabapentin and phenibut. Pregabalin contains a carboxylated chain of hexane called hexanoic acid. This carbon chain is substituted with an amine group through a methyl bridge in (S) conformation at R3 and a methyl group at R5.

Pharmacology

Pregabalin is neither a GABAA or GABAB receptor agonist

Pharmacodynamics

The pharmacological action of pregabalin is mediated by binding to the α2δ-1 site of voltage-gated calcium channels.[1][2] This site has also been referred to as the gabapentin receptor, as it is the target of the related substance gabapentin (also developed by Pfizer). Advantages to pregabalin over gabapentin include higher bioavailability and potency.

Although pregabalin is a chemical derivative of GABA, it displays no activity at any GABA receptors, including GABAA, GABAB and the benzodiazepine site. Pregabalin, despite its GABA backbone, does not appear to alter GABA levels in the brain, so its pharmacological activity is presumed to be unrelated to GABA.[3] Instead, it is its binding to the α2δ-1 site of voltage-gated calcium channels which appears to be the source of its subjective effects. By binding to this site, Pregabalin reduces the release of several excitatory neurotransmitters, including glutamate, substance P, acetylcholine and norepinephrine.

One study has also shown that pregabalin promotes deep sleep, thus enhancing sleep quality. This may be substantial because reductions in slow-wave sleep have been associated with anxiety and fibromyalgia.[4] Also, an independent action of the gabapentin site on the neurogenesis of excitatory synapses has been discovered. The endogenous neurochemical thrombospondin also binds to this site and is important for the generation of new excitatory synapses. Gabapentin and pregabalin, having a high affinity for this site, block this action and result in lower levels of excitatory synapses in animal models.[2]

As pregabalin treats conditions and neurotransmitters associated with overexcitability of the brain (anxiety, epilepsy, neuropathic pain), its modulation results in the sedating (or calming) effects of pregabalin on the nervous system.[citation needed]

Pharmacokinetics

Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within 1 to 1.5 hours. Pregabalin oral bioavailability is estimated to be greater than or equal to 90%. The rate of pregabalin absorption is decreased when given with food, resulting in delay of approximately 3 hours to reach peak plasma concentrations, with peak levels themselves, decreased by about 25 to 30%.[5] Administration with food, however, has no clinically significant effect on the extent of absorption.[6]

Pregabalin undergoes negligible metabolism in humans. In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The primary metabolite is N-methyl pregabalin.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged substance. Renal clearance of pregabalin is 73 mL/minute.[7]

Subjective effects

Each individual can have a very different reaction to pregabalin, thus it is essential to start at lower doses to ensure that it does not have any severe adverse effects such as peripheral edema or muscle pain. The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects
Child.svg

Visual effects
Eye.svg

Cognitive effects
User.svg

Auditory effects
Volume-up.svg

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

A box of 75mg capsules of Pfizer brand 'Lyrica' (pregabalin)

Therapeutic applications

Pregabalin is used in a medical setting, usually prescribed in capsules, to treat epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. Its use for epilepsy is as an add-on therapy for partial seizures with or without secondary generalization in adults. Some off-label uses of pregabalin include restless leg syndrome, prevention of migraines, social anxiety disorder, and alcohol withdrawal.

Seizures

Pregabalin is useful when added to other treatments, when those other treatments are not controlling partial epilepsy. Its use alone is less effective than some other seizure medications. It is unclear how it compares to gabapentin for this use.

Neuropathic pain

The European Federation of Neurological Societies recommends pregabalin as a first line agent for the treatment of pain associated with diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain. A minority obtain substantial benefit, and a larger number obtain moderate benefit. Other first line agents, including gabapentin and tricyclic antidepressants, are given equal weight as first line agents, and unlike pregabalin, are available as less expensive generics.

Anxiety disorders

The World Federation of Biological Psychiatry recommends pregabalin as one of several first line agents for the treatment of generalized anxiety disorder, but recommends other agents such as SSRIs as first line treatment for obsessive-compulsive disorder and post-traumatic stress disorder. It appears to have anxiolytic effects similar to benzodiazepines with less risk of dependence.

The effects of pregabalin appear after 1 week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychosomatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance, and, in addition, unlike benzodiazepines, it has a beneficial effect on sleep and sleep architecture, characterized by the enhancement of slow-wave sleep. It produces less severe cognitive and psychomotor impairment compared to those drugs and may be preferred over the benzodiazepines for these reasons.

Addiction to or withdrawal from other substances

Opioids

Anecdotal reports[15] exist of successful discontinuation of opioid use by supplementing with Pregabalin.

Tobacco

One placebo-controlled four-day trial (n=24 completed) investigated the effects of pregabalin on smoking cessation in non-treatment-seeking smokers.[16] This study did not find any statistically significant effect on smoking behavior, although pregabalin reduced some withdrawal symptoms: anxiety, irritability, and frustration. Pregabalin also reduced the measure of subjective "liking" after smoking a cigarette.

In summary, pregabalin has shown some promise as a treatment for addiction in controlled trials, particularly for benzodiazepine and alcohol abuse, and more anecdotally for opioid abuse.

Alcohol

A meta-review of five studies concerning the use of pregabalin in treating alcoholism or alcohol withdrawal found positive results for relapse prevention in sober patients at dosages of 150-450 mg/day, but conflicting results for the treatment of acute alcohol withdrawal.[17] Two of the studies concerned the only maintenance of abstinence. Both showed positive results. In one of them (n=59), pregabalin compared favorably to naltrexone on the measure of days abstinent from any amount of alcohol.

Three of the studies reviewed the concerned management of acute withdrawal symptoms. One of the studies (n=111) compared max 450mg/day pregabalin; max 800mg/day Tiapride (a dopamine antagonist), and max 10mg/day lorazepam for 14 days on the reduction of withdrawal symptoms and maintenance of abstinence from alcohol. All three groups experienced lessened withdrawal symptoms. The pregabalin group had the highest number of patients who remained alcohol-free.

A second study of detoxified patients (n=40) found a significant improvement in withdrawal symptoms from doses of pregabalin 200-450mg/day for seven days followed by seven days of gradual discontinuation. The third study on pregabalin-assisted withdrawal was placebo controlled (n=41) This was the only one of the three studies on pregabalin-assisted withdrawal to be placebo controlled, and the only one which did not find a positive result (not statistically significantly better results than placebo). Note that out of these three studies, the only one to find a negative result employed the smallest doses for the shortest amount of time (2 days of 400mg, two days 300mg, two days 200mg). The demographics were also unbalanced: the pregabalin group was significantly older. However, it was the only double-blind placebo-controlled trial surveyed. On the other hand, the trials with active comparator substances were positive.

Benzodiazepines

One open-label pilot study[18] of 15 individuals with high-dose benzodiazepine dependence reported that all subjects have successfully discontinued benzodiazepines within 14 weeks, while taking supplemental doses of 225-900mg pregabalin/day. The patients also showed reduced anxiety levels and better cognitive functioning. Pregabalin was well tolerated.

A larger study[19] tested pregabalin supplementation in the gradual taper of 282 long-time users of benzodiazepines (mean time two years). Around half, the participants used benzodiazepines on doctor's prescription, while the other half were self-medicating or did both. Patients supplemented a 12-week taper with average daily doses, by week 12, of pregabalin 315 mg/day, with a dose range of 25 to 600 mg/day. 62% of patients received pregabalin monotherapy while the remaining 38% supplemented pregabalin with other substances, most commonly various benzodiazepines. The success rate (benzo free at the end of the trial) was 52% for the whole cohort, and 70% for those who completed the 12-week follow-up (211/282 patients). The success rate in patients who received pregabalin as monotherapy was 49% compared to 58% in those receiving pregabalin in combination with other substances. Pregabalin also caused a significant reduction in the Hamilton Anxiety Scale and by the end of the trial a 60% reduction in withdrawal symptoms.

Toxicity and harm potential

Pregabalin likely has a low toxicity relative to dose. However, it is potentially lethal when mixed with depressants like alcohol or opioids.

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

Both rat and mouse oral acute LD50 have been established to be greater than 5000mg/kg. Rat IV LD50 was also determined to be greater than 300mg/kg.[20]

In terms of humans, there exists a case report of a man who ingested 8,400mg pregabalin and eventually fell into a coma but was managed with supportive care alone until he regained consciousness.[21] For comparison, the maximum recommended a therapeutic dose of pregabalin is 300mg twice per day. Another case report details a man's suicide attempt with the co-ingestion of an estimated 11.5 grams of pregabalin and 32 grams of lamotrigine, another anti-epileptic agent which, by blocking sodium channels, lowers glutamate levels similar to pregabalin. He presented with a reduced level of consciousness and an aggressive demeanor when not sedated. Eventually, he suffered respiratory problems that required intubation and ventilation. After 28 days in the hospital (19 of which were in the intensive care unit) the man was discharged from the hospital. The man suffered seizures which were attributed to his underlying epilepsy.[22] Pfizer's official package insert for Lyrica states that the highest accidental ingestion of pregabalin during clinical trials was 8 g, with no significant consequences.[23]

Tolerance and addiction potential

Pregabalin is minimally physically and psychologically addictive.

Tolerance will develop to the depressant effects within several months of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. Withdrawal symptoms or rebound symptoms are likely to occur after ceasing usage abruptly following a few months or longer of steady dosing and may necessitate a gradual dose reduction.

The withdrawal effects of abrupt cessation of chronic use include anxiety, insomnia, sweating, muscle spasms, gastrointestinal problems, hot and cold flashes, nausea, and a flu-like feeling. There exist reports of patients with history of both opioid and benzodiazepine abuse who considered pregabalin withdrawal to be worse than benzodiazepine or heroin withdrawal.[24]

Pregabalin was initially thought to be non-addictive with a low abuse potential and little tolerance development. However, recreational use of the substance has caused a re-evaluation of this assessment. The euphoric effects of the substance and the development of tolerance can lead to the use of dosages far above the therapeutic range. Pregabalin is indubitably both recreational and addictive.[25][26]

Interactions

One report of a patient entering serotonin syndrome following perioperative oxycodone and pregabalin exists.[27] However, several studies have failed to find any serotonergic effect whatsoever from pregabalin. One paper states, "Although pregabalin is a structural analog of GABA, it has no clinically significant effects at GABA-A or GABA-B receptors, and it is not converted metabolically into GABA or a GABA agonist. Pregabalin is not a serotonin reuptake inhibitor and does not act as a glutamate receptor antagonist."[28] A more recent study writes that "Pregabalin has no involvement with serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake."[29] Pregabalin's main mechanism of action is binding and blocking sub receptor on Voltage-Gated Calcium Channels, leading to a downstream reduction of overactive neurons.

If pregabalin has serotonergic effects, it could interact negatively with other serotonergic substances, including SSRIs, MDMA, various analgesics, and possibly other recreational and medical substances. Given the total lack of evidence for any serotonergic activity in multiple studies, it seems possible that the one reported adverse event was a freak accident, caused by unknown factors.

Legality

Handcuffs-300px.png

This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

Pregabalin is regulated as a prescription drug in most countries.

  • Norway: Pregabalin is in prescription schedule C, the lowest schedule, although it has been suggested that it should be moved to Class B alongside benzodiazepines.[30]
  • Sweden: Lyrica is a prescription-only drug and is not currently classified as a narcotic.[31][32]
  • United Kingdom: Pregabalin is currently regulated as a Prescription-Only Medicine and not scheduled. The Advisory Council on the Misuse of Drugs recently recommended that the substance should be placed in Class C of the Misuse of Drugs Act. This recommendation comes on the heels of two teenage overdose deaths where Lyrica was part of a cocktail of depressants. One of the deceased, a Belfast teenager, died after mixing tramadol, Lyrica, diazepam and alcohol.[33]
  • United States: Pregabalin is in Schedule V, indicating "low potential for abuse." For comparison, benzodiazepines are in Schedule IV.[34]

See also

External links

Literature

  • Field, M. J., Cox, P. J., Stott, E., Melrose, H., Offord, J., Su, T., … Williams, D. (2006). Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17537–42. https://doi.org/10.1073/pnas.0409066103
  • Eroglu, Ç., Allen, N. J., Susman, M. W., O’Rourke, N. A., Park, C. Y., Özkan, E., … Barres, B. A. (2009). Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis. Cell, 139(2), 380–392. https://doi.org/10.1016/j.cell.2009.09.025
  • Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel ??2-?? (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008
  • Hindmarch, I., Dawson, J., & Stanley, N. (2005). A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep, 28(2), 187–93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16171242
  • Wood, D. M., Berry, D. J., Glover, G., Eastwood, J., & Dargan, P. I. (2010). Significant Pregabalin Toxicity Managed with Supportive Care Alone. Journal of Medical Toxicology, 6(4), 435–437. https://doi.org/10.1007/s13181-010-0052-3
  • Braga, A. J., & Chidley, K. (2007). Self-poisoning with lamotrigine and pregabalin. Anaesthesia, 62(5), 524–527. https://doi.org/10.1111/j.1365-2044.2006.04913.x
  • Kavoussi, R. (2006). Pregabalin: From molecule to medicine. European Neuropsychopharmacology, 16, S128–S133. https://doi.org/10.1016/j.euroneuro.2006.04.005
  • Song, H.-K. (2013). Serotonin syndrome with perioperative oxycodone and pregabalin. Pain Physician, 16(October), E632-3. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24077214
  • Herman, A. I., Waters, A. J., McKee, S. A., & Sofuoglu, M. (2012). Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers. Psychopharmacology, 220(3), 611–617. https://doi.org/10.1007/s00213-011-2507-x
  • Guglielmo, R., Martinotti, G., Clerici, M., & Janiri, L. (2012). Pregabalin for alcohol dependence: A critical review of the literature. Advances in Therapy, 29(11), 947–957. https://doi.org/10.1007/s12325-012-0061-5
  • Kämmerer, N., Lemenager, T., Grosshans, M., Kiefer, F., & Hermann, D. (2012). [Pregabalin for the reduction of opiate withdrawal symptoms]. Psychiatrische Praxis, 39(7), 351–2. https://doi.org/10.1055/s-0032-1305042
  • Bobes, J., Rubio, G., Terán, A., Cervera, G., López-Gómez, V., Vilardaga, I., & Pérez, M. (2012). Pregabalin for the discontinuation of long-term benzodiazepines use: An assessment of its effectiveness in daily clinical practice. European Psychiatry, 27(4), 301–307. https://doi.org/10.1016/j.eurpsy.2010.12.004
  • Oulis, P., Konstantakopoulos, G., Kouzoupis, A. V., Masdrakis, V. G., Karakatsanis, N. A., Karapoulios, E., … Papadimitriou, G. N. (2008). Pregabalin in the discontinuation of long-term benzodiazepines’ use. Human Psychopharmacology: Clinical and Experimental, 23(4), 337–340. https://doi.org/10.1002/hup.937

References

  1. Field, M. J., Cox, P. J., Stott, E., Melrose, H., Offord, J., Su, T., … Williams, D. (2006). Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17537–42. https://doi.org/10.1073/pnas.0409066103
  2. 2.0 2.1 Eroglu, Ç., Allen, N. J., Susman, M. W., O’Rourke, N. A., Park, C. Y., Özkan, E., … Barres, B. A. (2009). Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis. Cell, 139(2), 380–392. https://doi.org/10.1016/j.cell.2009.09.025
  3. Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel  α2–δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008
  4. Hindmarch, I., Dawson, J., & Stanley, N. (2005). A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep, 28(2), 187–93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16171242
  5. https://www.drugs.com/ppa/pregabalin.html
  6. http://web.archive.org/web/20160305012454/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000546/WC500046602.pdf
  7. http://web.archive.org/web/20160305071130/http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=41099
  8. Time to improvement of pain and sleep quality in clinical trials of pregabalin for the treatment of fibromyalgia. | https://www.ncbi.nlm.nih.gov/pubmed/25529830
  9. Pregabalin beneficial effects on sleep quality or health-related quality of life are poorly correlated with reduction on pain intensity after an 8-week treatment course. | https://www.ncbi.nlm.nih.gov/pubmed/22156921
  10. Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915349/
  11. Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206785/
  12. Pregabalin | http://www.epilepsy.com/medications/pregabalin
  13. Pregabalin for the management of partial epilepsy | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646650/
  14. Abuse and Misuse Potential of Pregabalin: A Review of the Clinical Evidence. (2012, April 12). Retrieved December 26, 2016, from Canadian Agency for Drugs and Technologies in Health, http://www.dpic.org/sites/default/files/PregabalinAbuse_CADTH_24Apr2012.pdf
  15. Kämmerer, N., Lemenager, T., Grosshans, M., Kiefer, F., & Hermann, D. (2012). [Pregabalin for the reduction of opiate withdrawal symptoms]. Psychiatrische Praxis, 39(7), 351–2. https://doi.org/10.1055/s-0032-1305042
  16. Herman, A. I., Waters, A. J., McKee, S. A., & Sofuoglu, M. (2012). Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers. Psychopharmacology, 220(3), 611–617. https://doi.org/10.1007/s00213-011-2507-x
  17. Guglielmo, R., Martinotti, G., Clerici, M., & Janiri, L. (2012). Pregabalin for alcohol dependence: A critical review of the literature. Advances in Therapy, 29(11), 947–957. https://doi.org/10.1007/s12325-012-0061-5
  18. Oulis, P., Konstantakopoulos, G., Kouzoupis, A. V., Masdrakis, V. G., Karakatsanis, N. A., Karapoulios, E., … Papadimitriou, G. N. (2008). Pregabalin in the discontinuation of long-term benzodiazepines’ use. Human Psychopharmacology: Clinical and Experimental, 23(4), 337–340. https://doi.org/10.1002/hup.937
  19. Bobes, J., Rubio, G., Terán, A., Cervera, G., López-Gómez, V., Vilardaga, I., & Pérez, M. (2012). Pregabalin for the discontinuation of long-term benzodiazepines use: An assessment of its effectiveness in daily clinical practice. European Psychiatry, 27(4), 301–307. https://doi.org/10.1016/j.eurpsy.2010.12.004
  20. Lyrica material data sheet | http://web.archive.org/web/20161203214718/http://www.pfizer.com/files/products/material_safety_data/722.pdf
  21. Wood, D. M., Berry, D. J., Glover, G., Eastwood, J., & Dargan, P. I. (2010). Significant Pregabalin Toxicity Managed with Supportive Care Alone. Journal of Medical Toxicology, 6(4), 435–437. https://doi.org/10.1007/s13181-010-0052-3
  22. Braga, A. J., & Chidley, K. (2007). Self-poisoning with lamotrigine and pregabalin. Anaesthesia, 62(5), 524–527. https://doi.org/10.1111/j.1365-2044.2006.04913.x
  23. Lyrica package insert | http://labeling.pfizer.com/ShowLabeling.aspx?id=561#section-10
  24. Lyrica – norske bivirkningsmeldinger om misbruk | http://web.archive.org/web/20150910231010/http://www.relis.no/Bivirkninger/Nytt_om_bivirkninger/2014/Misbruk_avhengighet_og_seponeringsreaksjoner_ved_bruk_av_Lyrica_norske_bivirkningsmeldinger
  25. Ja, pregabalin kan misbrukes! | http://web.archive.org/web/20160407131805/http://tidsskriftet.no/article/2029812
  26. Gabapentin and pregabalin: abuse and addiction. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/22822593
  27. Song, H.-K. (2013). Serotonin syndrome with perioperative oxycodone and pregabalin. Pain Physician, 16(October), E632-3. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24077214
  28. Kavoussi, R. (2006). Pregabalin: From molecule to medicine. European Neuropsychopharmacology, 16, S128–S133. https://doi.org/10.1016/j.euroneuro.2006.04.005
  29. David M. Marks et al. 2009. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796047/
  30. http://web.archive.org/web/20160510044256/http://felleskatalogen.no/medisin/lyrica-pfizer-561166
  31. http://web.archive.org/web/20161225014001/http://www.fass.se/LIF/product?nplId=20040607000748
  32. http://web.archive.org/web/20160918161743/http://www.riksdagen.se/sv/dokument-lagar/dokument/svensk-forfattningssamling/forordning-19921554-om-kontroll-av-narkotika_sfs-1992-1554
  33. http://www.bbc.com/news/uk-northern-ireland-36297527
  34. http://web.archive.org/web/20161017105621/https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_15.htm