Drug Profile

Pregabalin (LYRICA) was approved by the Food and Drug Administration (FDA) in 2004 to treat neuropathic pain (sharp, severe pain originating along the course of a nerve) in diabetics with peripheral neuropathy, patients with post-herpes (shingles) pain and patients experiencing partial-onset seizures. In 2007, it also was approved to treat fibromyalgia (muscle pain, stiffness and fatigue).[2]

Despite the FDA's decision to approve this drug to treat these types of neuropathic pain, we recommend that you not use it for these purposes.

Pregabalin may control these conditions, but it does not cure them, nor any off-label conditions for which it may be prescribed. It belongs to the same drug family as gabapentin (NEURONTIN), a drug that was illegally promoted for many off-label uses despite a lack of evidence of its effectiveness for these indications.[3]

Patients taking pregabalin should start with the lowest recommended dose. If necessary, the prescribing physician should increase the dose gradually. People with kidney problems or who are on dialysis may need dose adjustments.[3],[4]

Adverse effects

Common adverse effects of pregabalin include dizziness, vision changes and weight gain, which can be rapid and dramatic.[5] This drug is a controlled substance with a potential for abuse.[6] Adverse effects, including muscle twitches, occur more frequently with higher doses.[7]

Pregabalin may decrease platelets or cause fluid retention.[1],[8]

If you are stopping use of pregabalin, follow your doctor's instructions to lower the dose of the drug gradually over one week. Otherwise, seizures may occur.[1] There have been reports of brain swelling due to abruptly stopping use of pregabalin.[9]

There have been case reports of worsening chronic heart failure in patients using pregabalin.[10] Prescrire International published an article in 2014 on reports of cardiac adverse effects, including abnormal heart rhythms, in patients taking pregabalin.[11] Pregabalin should be used with caution in patients with heart failure and other types of heart disease.[12]

Studies say...

A 2006 study presented evidence of erectile dysfunction in men using pregabalin. This study was co-authored by a researcher from Pfizer, manufacturer of pregabalin and sildenafil (VIAGRA). The report contains previously unpublished Pfizer data showing significant increases in sexual dysfunction in both men and women using pregabalin compared with those using a placebo. For men, there were significant increases in impotence and decreased libido. For women, there were significant increases in anorgasmia (failure to have an orgasm) and decreased libido.[13]

In 2016, CNS Drugs published a systematic review of the potential risk of abuse associated with pregabalin.[14]

Pregabalin for Pain: Do Not Use

Pregabalin has three approved uses for pain:

• Management of peripheral neuropathy in people with diabetes. This type of pain occurs in about 15% of people with diabetes.[15],[16],[17],[18]
• Management of postherpetic neuralgia, a pain that lasts for three months after a rash due to herpes. This happens to about 10% of people who have herpes zoster. The pain often disturbs sleep.[19],[20],[21],[22]
• Management of fibromyalgia

The primary FDA reviewer responsible for the applications for approval of pregabalin for diabetic neuropathy and postherpetic neuralgia concluded that the drug should not be approved for these indications. In his discussion of the application for postherpetic neuralgia, he stated that "overall the risk of adverse effects of treatment approach or exceed the likelihood of treatment benefit." Similarly, he recommended against the approval for diabetic neuropathy, stating that "it does not appear that the benefits of the drug in patients with diabetic neuropathy outweigh the risks."

The reviewer's concerns about risks involved statistically significant increases in visual abnormalities in patients using pregabalin as well as a higher incidence of accidental injuries and edema. Among pregabalin users there was a 4.3-fold increase in blurred vision and a 6.7-fold increase in double vision compared with those taking a placebo. Accidental injuries occurred nine times more frequently in pregabalin users. One possible explanation for the increased injuries is significant increases in dizziness and abnormal gait in people using pregabalin.

Despite the reviewer's concerns, his supervisors overruled him and the drug was approved for these two indications.[23] After the drug's approval, one review of its performance rated the evidence for pregabalin for neuropathic pain as "limited."[24]

We oppose the use of pregabalin for treatment of fibromyalgia because it is not clear that the benefits of using the drug for this difficult-to-define condition clearly outweigh the risks.

Pregabalin often is prescribed for sciatica, a type of neuropathic pain characterized by aching, burning or sharp pain sensations that typically occur on one side of the body and radiate from the buttock down the back or side of the leg. The drug has not been approved by the FDA for this use. In 2017, the New England Journal of Medicine published results of a clinical trial showing that pregabalin was not effective in treating sciatica and was associated with an increased risk of harm.[25]

Pregabalin for partial-onset seizures: Limited Use

Pregabalin is approved as a treatment to supplement the effects of another drug for partial-onset seizures. It can be used with other antiseizure medications such as carbamazepine (CARBATROL, TEGRETOL), lamotrigine (LAMICTAL), phenytoin (DILANTIN) or valproic acid to increase their overall effectiveness.[26]

Many patients who experience partial-onset seizures have an inadequate response to available drugs. Up to 12% of adults facing this condition may become seizure-free with pregabalin.[27],[28],[29],[7],[30]

Regulatory actions surrounding pregabalin

In 2008, the FDA issued a warning that there have been reports of suicidal behavior or ideation associated with the use of antiepileptic drugs, including pregabalin. According to the study, patients receiving these drugs had twice the risk of suicidal behavior or ideation compared with patients receiving placebo, and this increased risk was observed as early as one week after starting the drug.[31]

In 2008, the FDA issued another advisory stating that it had completed its analysis of reports of suicidality (suicidal behavior or ideation [thoughts]) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders and other conditions. Based on the outcome of this review, the FDA is requiring that all manufacturers of drugs in this class include a warning in their labeling and develop a Medication Guide to be provided to patients who are prescribed these drugs to inform them of the risks of suicidal thoughts or actions.[32]

In 2019, the Medicines and Healthcare products Regulatory Agency (a regulatory agency in the United Kingdom similar to the FDA) announced that pregabalin is now classified as a controlled substance.[33]

In 2019, Health Canada (a regulatory agency in Canada similar to the FDA) issued an advisory that there is an increased risk of adverse effects, including opioid overdose, when gabapentin or pregabalin is used together with opioid medications.[34]

In 2019, the FDA issued an advisory that serious breathing problems can occur when gabapentin or pregabalin is used in the elderly and in patients who are at risk of breathing difficulties, including those taking opioids and other drugs that depress breathing through their effects on the central nervous system.[35] The agency also required that the product labeling be updated to include a warning about this risk.[36]

In 2022, the Medicines and Healthcare products Regulatory Agency (agency in the U.K. similar to the FDA) issued an advisory about a new study suggesting that pregabalin was associated with a slightly increased risk of malformations in the fetus when used during pregnancy.[37]