Pregabalin


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, generalized anxiety disorder, and postherpetic neuralgia. Pregabalin also has antiallodynic properties. Its use in epilepsy is as an add-on therapy for partial seizures. When used before surgery, it reduces pain but results in greater sedation and visual disturbances. It is taken by mouth.
Common side effects can include headache, dizziness, sleepiness, euphoria, confusion, trouble with memory, poor coordination, dry mouth, problems with vision, and weight gain. Serious side effects may include angioedema, kidney damage, and seizures.
As with all other drugs approved by the FDA for treating epilepsy, the pregabalin labeling warns of an increased suicide risk when combined with other drugs. When pregabalin is taken at high doses over a long period of time, addiction may occur, but if taken at usual doses the risk is low. Use during pregnancy or breastfeeding is of unclear safety.
It is a gabapentinoid medication which is a class of drugs within the derivatives of γ-aminobutyric acid, an inhibitory neurotransmitter. Although pregabalin is inactive at GABA receptors and GABA synapses, it acts by binding specifically to the α2δ-1 protein that was first described as an auxiliary subunit of voltage-gated calcium channels.
Pregabalin was approved for medical use in the United States in 2004. In the US, pregabalin is a Schedule V controlled substance under the Controlled Substances Act of 1970, which means that the drug has low abuse potential compared to substances in Schedules I-IV, however, there is still a potential for misuse. It is available as a generic medication. In 2023, it was the 78th most commonly prescribed medication in the United States, with more than 8million prescriptions.

Medical uses

Seizures

For drug-resistant focal epilepsy, pregabalin is useful as an add-on therapy to other treatments. 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. It is given equal weight as gabapentin and tricyclic antidepressants as a first-line agent, however, the latter are less expensive as of 2010. Pregabalin is as effective at relieving pain as duloxetine and amitriptyline. Combination treatment of pregabalin and amitriptyline or duloxetine offers additional pain relief for people whose pain is not adequately controlled with one medication and is safe.
Studies have shown that higher doses of pregabalin are associated with greater efficacy.
Pregabalin's use in cancer-associated neuropathic pain is controversial, though such use is common. It has been examined for the prevention of post-surgical chronic pain, but its utility for this purpose is controversial.
Pregabalin is generally not regarded as efficacious in the treatment of acute pain. In trials examining the utility of pregabalin for the treatment of acute post-surgical pain, no effect on overall pain levels was observed, but people did require less morphine and had fewer opioid-related side effects. Several possible mechanisms for pain improvement have been discussed.

Anxiety disorders

Pregabalin is effective for treatment of generalized anxiety disorder. It is also effective for the short- and long-term treatment of social anxiety disorder and in reducing preoperative anxiety. 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.
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 those of the selective serotonin reuptake inhibitor class as first line treatment for obsessive–compulsive disorder and post-traumatic stress disorder. For PTSD, pregabalin as complementary treatment seems to be effective.

Generalized anxiety disorder

Pregabalin has anxiolytic effects similar to benzodiazepines with less risk of dependence. The effects of pregabalin appear within one week of use, and are similar in effectiveness to lorazepam, alprazolam, and bromazepam, 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 benzodiazepines.
A 2019 review found that pregabalin reduces symptoms, and was generally well tolerated.

Other uses

Although pregabalin is sometimes prescribed for people with bipolar disorder, there is no evidence showing that it is effective.
There is no evidence and significant risk in using pregabalin for sciatica and low back pain.
Evidence of benefit in alcohol withdrawal as well as withdrawal from certain other drugs is limited as of 2016.
There is no evidence for its use in the prevention of migraines and gabapentin has also been found not to be useful.
A 2025 review found possible benefits to sleep quality in patients with fibromyalgia.

Adverse effects

In a systematic review analysing data from 5 cohort studies having 1,085,488 patients, use of gabapentinoids was associated with an increased risks of thrombotic events as early as three months of use, and with increased risk of cardiovascular events on prolonged use of more than a year duration. Heart failure was not increased with the use of gabapentinoids.
Exposure to pregabalin is associated with weight gain, drowsiness, fatigue, dizziness, vertigo, leg swelling, disturbed vision, loss of coordination, and euphoria. It has an adverse effect profile similar to other central nervous system depressants. Even though pregabalin is a depressant and anticonvulsant, it can sometimes paradoxically induce seizures, particularly in large overdoses. Adverse drug reactions associated with the use of pregabalin include:
Cases of recreational use, with associated adverse effects, have been reported.

Withdrawal symptoms

Following abrupt or rapid discontinuation of pregabalin, some people reported symptoms suggestive of physical dependence. The FDA determined that the substance dependence profile of pregabalin, as measured by a personal physical withdrawal checklist, was quantitatively less than benzodiazepines.
Even people who have discontinued short-term use of pregabalin have experienced withdrawal symptoms including insomnia, headache, heart palpitations, nausea, anxiety, diarrhea, flu-like symptoms, major depression, pain, seizures, excessive sweating, muscle twitching, and dizziness.
A tapered discontinuation is recommended to reduce the chances of withdrawal symptoms. Lyrica's US package insert recommends a taper period of at least one week. Best Practice Advocacy Centre New Zealand and NHS Somerset recommend a much slower withdrawal.

Pregnancy

It is unclear if it is safe for use in pregnancy with some studies showing potential harm.

Breathing

In December 2019, the US Food and Drug Administration warned about serious breathing issues for those taking gabapentin or pregabalin when used with central nervous system depressants or for those with lung problems.
The FDA required new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. The FDA also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression.
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.
The FDA reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries. The FDA also reviewed several animal studies that showed pregabalin alone and pregabalin plus opioids can depress respiratory function.