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Pregabalin (Lyrica) is approved for neuropathic pain in diabetes, spinal cord injury, post-herpetic pain, fibromyalgia, and generalized and social anxiety. It is also used off-label for pain due to chemotherapy, pruritus, or surgery, and in restless leg syndrome. Find out more about its uses, mechanisms, side effects, and potential for drug abuse/addiction.

Note: By writing this post, we are not recommending this drug.  Some of our readers who were already taking the drug requested that we commission a post on it and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

Introduction

Pregabalin (Lyrica), a successor to gabapentin, was approved for the treatment of neuropathic pain, refractory epilepsy, and fibromyalgia [R].

Its off-label uses in the US include postoperative pain and generalized anxiety disorder [R, R].

Mechanism of Action

Pregabalin is similar in structure to GABA [R].

It attaches to calcium channels in the neurons of the brain and spine and reduces the excessive excitation of nerves [R].

It also increases the density of GABA transporter proteins and increases the rate of GABA transport [R].

The pain-reducing, anti-seizure, and anxiety-relieving effects are due to the decrease of excitatory neurotransmitters, including glutamate and substance P, in the brain and spinal cord [R, R].

Pregabalin also inhibits the activity of NMDA receptors and provides pain relief by blocking the sensation of pain in the nerves [R].

Pregabalin Uses

1) Pregabalin Reduces Nerve Pain

Pregabalin is effective in reducing pain caused by nerve damage, like peripheral diabetic neuropathy, fibromyalgia, or chemotherapy-induced neuropathic pain [R].

A review of clinical studies concluded that pregabalin is the “most effective agent” in reducing neuropathic pain, either alone or in combination with other drugs when cost-effectiveness, tolerance, and general improvement in pain state are considered [R].

Pregabalin provides greater pain relief and has fewer adverse effects than gabapentin [R].

Also, patients who respond to gabapentin achieve further relief without additional adverse effects with pregabalin [R].

In a study of 32 patients who responded to gabapentin and 29 non-responders, gabapentin was replaced by pregabalin. Both groups experienced an additional neuropathic pain relief of 25% after 6 and 12 months of use. However,  gabapentin non-responders stopped using pregabalin in more than 30% of cases due to ineffectiveness or side effects [R].

Pregabalin Improves Diabetic Neuropathy

Currently, only duloxetine, pregabalin, and tapentadol are approved in the US for diabetic neuropathy [R].

Several clinical trials have shown the effectiveness of pregabalin in the management of diabetic nerve pain [R, R].

A systematic review of 4 clinical trials (of 1,068 patients with diabetic neuropathy), concluded that this drug relieved pain significantly better than the placebo [R].

Pregabalin Relieves Pain Caused by Shingles

In shingles, the pain sometimes persists for more than 3 months after the rash has healed (postherpetic neuralgia) [R].

In a study (DB-RCT) of 238 patients with postoperative neuralgia, pregabalin relieved pain and reduced pain-related sleep disturbances [R].

Another review of 9 clinical trials showed the same results [R].

Pregabalin Relieves Pain in Spinal Cord Injury

In a randomised trial, 220 spinal cord injury patients received this drug or placebo for 17 weeks. Pregabalin relieved pain since week 1, and the effect remained consistent throughout the treatment [R].

Both gabapentin and pregabalin are effective for this condition. However, review of the literature suggests that pregabalin is better than gabapentin even with reduced dosage [R].

2) Pregabalin Improves Quality of Life For People with Fibromyalgia

Fibromyalgia syndrome is a disorder of chronic widespread pain. It includes symptoms such as fatigue, poor quality of sleep (unrefreshing, nonrestorative sleep), depression, anxiety, and muscle and joint stiffness [R].

Pregabalin was the first medication approved by the FDA for the management of fibromyalgia [R].

This drug is different from other fibromyalgia medications as it is an anticonvulsant and not an antidepressant [R].

Fibromyalgia patients have increased levels of glutamate and substance P. Pregabalin can have calming or sedative effects as it can reduce excess levels of these two neurotransmitters  [R, R, R].

Pregabalin also improves the quality of life and functional ability in fibromyalgia patients.

At least 2 meta-analyses (5 RCTs, >3000 patients) concluded that pregabalin reduces symptoms of pain, anxiety, and fatigue, and improves general working ability and sleep quality in fibromyalgia patients [R, R].

A systematic review of 8 studies showed that pregabalin reduces pain intensity by 30 to 50% over 12 to 26 weeks in 10% of patients having moderate or severe pain due to fibromyalgia. Quality of life and function also improved with pain relief [R].

3) Pregabalin Helps Relieve Chronic Back Pain

Pregabalin can be used as an “add-on” medicine for chronic back pain.

In a randomised double-blind prospective study of 36 patients, the combination of celecoxib and pregabalin was more effective than either drug alone for chronic low-back pain, with similar adverse effects [R].

In 409 patients with neuropathic pain, including chronic back pain, a combination of pregabalin and oxycodone provided better pain relief and overall wellness than either drug alone [R].

A systematic literature review found no evidence to support the use of pregabalin as a single-drug therapy for treatment of chronic lower back pain [R].

In sciatica patients (searing pain starting from the lower back, down the leg) treatment with pregabalin did not significantly reduce the intensity of leg pain as compared with placebo, over the course of 8 weeks [R].

4) Pregabalin Helps Reduce Epileptic Episodes

Pregabalin has anti-seizure properties. The FDA has approved it as an effective “add-on” drug in epilepsy treatment.

In patients with partial epilepsy (caused by brain injury), pregabalin is recommended as an “add-on” drug (adjunctive therapy) for patients that do not respond to other anti-epileptic drugs [R].

A meta-analysis of 8 studies (1911 patients) showed that at comparable doses, pregabalin reduced epileptic seizures by 50% or more. It was more effective than gabapentin [R].

There is insufficient research about the relative effectiveness of pregabalin compared with gabapentin as single-drug therapy for epilepsy [R].

5) Pregabalin Provides Relief for Social or Generalized Anxiety

Pregabalin is a well-established anti-anxiety agent that has gained approval in the EU, but not in the US, for the treatment of generalized anxiety disorder [R].

Short- and long-term clinical studies demonstrate that pregabalin is effective in the treatment of moderate to severe generalized anxiety in adults [R].

Based on a review of clinical studies, daily pregabalin is comparable to standard therapy with benzodiazepines or other anti-anxiety drugs and more effective than placebo in reducing symptoms in patients with social or generalized anxiety [R].

However, pregabalin does not reduce anxiety before surgical procedures.

In a dose-ranging study with 108 patients undergoing elective surgery, this drug was not effective in reducing anxiety before surgery or pain after [R].

Off-Label Uses

6) Pregabalin Can Reduce Neuropathic Pain in Pruritus (Itching)

Pregabalin is effective for several forms of pruritus, particularly itching due to kidney disease (uremic pruritus) and neural origin. It is a promising therapeutic option for pruritus patients not responding to usual treatments [R].

It is also effective in relieving pruritus (itching) and nerve pain in burn survivors [R].

In a study (DB-RCT) of 80 patients with moderate to severe pruritus, pregabalin removed itch or brought it down to tolerable limits. Patients with mild itch can also be treated with pregabalin in addition to massage and antihistamines for a quicker, predictable, and complete response [R].

7) Pregabalin for Restless Leg Syndrome

Restless legs syndrome is a nerve disorder in which the patient has an urge to move the legs. The symptoms become worse at night and disrupt sleep [R].

Pregabalin is effective as a short-term treatment for restless leg syndrome [R, R].

In a randomised, double-blind study, it was 90% efficient in reducing symptoms of the syndrome [R].

A 12-week DB-RCT with 58 patients demonstrated that it can relieve symptoms of restless leg syndrome and improve sleep [R].

8) Pregabalin Improves Sleep

In a DB-RCT with 85 restless leg syndrome patients showing sleep disturbance, pregabalin improved the depth of sleep by increasing slow wave sleep and reducing the number of sleep interruptions compared to placebo and pramipexole (restless leg syndrome treatment drug) [R].

A review concluded that this drug improved sleep quality, reduced awakenings, and increased slow wave sleep in different conditions (diabetic peripheral neuropathy, fibromyalgia, restless leg syndrome) [R].

The same review concluded that effects of this drug in improving sleep quality are inconsistent in partial epilepsy [R].

9) Pregabalin Can Relieve Chemotherapy-Induced Neuropathy

It is effective in reducing nerve pain due to chemotherapy.

Cancer patients undergoing chemotherapy have either a complete absence of pain or a significant reduction with pregabalin [R].

Furthermore, in a study involving 23 patients, oxaliplatin-induced peripheral neuropathy was reduced in 48% of patients with pregabalin [R].

10) Pregabalin May Relieve Postoperative Pain

There is contradicting evidence about the effectiveness of pregabalin in pain relief after surgery.

A DB-RCT with 80 patients concluded that pregabalin given before surgery, with or without lidocaine, reduced morphine requirements. It provided better pain relief compared to placebo in patients undergoing surgical procedures in the abdomen [R].

Pregabalin may also relieve pain after dental surgery.

In a DB-RCT, pregabalin was better than placebo or ibuprofen in relieving pain after dental surgery. Higher doses increased pain relief duration compared to ibuprofen but with more adverse effects [R].

In contrast, at least two literature reviews stated that there is no clear evidence that pregabalin before or after surgery reduced postoperative pain intensity. However, it did reduce the need for opioids in the first 24 hours after surgery and it also reduced opioid-related adverse effects, such as vomiting [R, R].

Dosage

This drug is available as 50, 75, 100, 150, 200, 225, and 300 mg tablets. The average daily dose ranges from 50 to 600 mg/day. It does not break down in the liver. Nearly 98% of the absorbed dose is excreted unchanged in urine [R].

The effectiveness and side effects of pregabalin (Lyrica) are both dose-related [R].

It is given orally with or without food. People start with lower doses and the desired dose is achieved slowly over time. Similarly, when discontinuing, the dose is reduced gradually over a minimum period of 1 week [R].

The initial dose is often 50 mg three times a day or 75 mg two times a day (for nerve pain associated with diabetes, surgery, fibromyalgia, and spinal cord injury) [R].

Maximum dose is 300-600 mg per day, depending on the condition [R].

In restless leg syndrome, pregabalin is given in the evening (50 – 300 mg per day) rather than as divided doses throughout the day [R].

Note: This information is not intended to replace a consultation with your doctor.

Pregabalin Overdose

The highest reported accidental overdose with Lyrica during trials was 8,000 mg, without notable clinical consequences [R].

If an overdose occurs, the drug can be extracted by stomach pumping or hemodialysis [R].

Safety and Contraindications

This drug is contraindicated in patients with known hypersensitivity to pregabalin or any of its components [R].

Patients undergoing hemodialysis or with reduced kidney function need to consult their physician and adjust the daily dose accordingly [R].

Pregabalin in Pregnancy

Pregabalin is a category C drug [R]. This means that:

  • Animal studies (mice and rabbits) showed signs of adverse effects on the fetus
  • There have been no adequate and well-controlled studies in pregnant women
  • The potential benefits of the drug may outweigh the possible adverse effects

Pregnant women should take caution while taking pregabalin.

A study compared 164 pregabalin exposed pregnancies with 656 controls and found a significantly higher rate of major birth defects among women receiving pregabalin [R].

However, a later study included 477 pregabalin exposed women and did not confirm any birth defects in newborns, although the possibility of a small effect was not ruled out [R].

Pregabalin Side Effects

Pregabalin is generally well tolerated and associated with temporary mild to moderate adverse effects, which depend on the dose [R].

1) Weight Gain

Weight gain is one of the side effects of this drug. However, the majority of patients treated with it maintain weight within a 7% range [R].

The percentage of pregabalin-treated patients who withdrew from a clinical study due to weight gain is very low (0.3%) [R].

Pregabalin-associated weight gain is related to dose and duration of the treatment [R].

Weight gain and edema were observed in patients taking this drug in combination with some glucose-lowering medications [R].

2) Suicidal Tendencies

An observational cohort study that monitored pregabalin side effects in 1,373 patients found two cases of suicidal ideation linked with pregabalin use [R].

Additionally, several case reports suggested that this drug caused suicidal behaviors [R, R, R].

Pregabalin can cause suicidal thoughts or actions in about 1 in 500 people [R].

However, in a cohort study with 7,875 pregabalin patients, this drug was not associated with an increased risk of suicide [R].

3) Erectile Dysfunction and Decreased Fertility

erectile dysfunction

At least 1 in 100 patients experience erectile dysfunction (impotence) as a side effect of pregabalin [R, R].

Signs of reduced fertility, decreased sperm count and motility, were observed in rats given pregabalin at concentration 6 times higher than the maximum recommended dose. The fertility effects were reversible during the 3-4 months of the study [R].

In female rats, the reproductive cycle was disrupted at higher doses [R].

However, clinical data is insufficient to clearly state whether this drug has an effect on male or female fertility in humans.

In 30 healthy men, 3 months of treatment (one complete sperm cycle) resulted in less than 4% decrease in sperm motility [R].

Other Side Effects

Most frequent adverse reactions (these are dose-dependent)[R]:

  • Dizziness [R]
  • Sedation [R]
  • Excessive sleepiness (somnolence) [R]
  • Swelling of hands and feet (peripheral edema) [R]
  • Blurred vision [R]

Patients should avoid operating heavy machinery until they determine how this drug will affect them [R].

Serious, even life-threatening, adverse effects [R]:

  • Allergic reactions
  • Swelling of face, mouth, lips, gums, tongue, throat, or neck
  • Trouble breathing
  • Rash, hives (raised bumps), or blisters

Stopping the use of pregabalin suddenly can cause [R]:

These symptoms are similar to physical dependence (withdrawal) [R].

Drug Interactions

Unlike most drugs, pregabalin is not broken down in the liver, hence no drug interactions in the liver are reported [R].

Pregabalin clearance by the kidneys decreases with nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, and cyclosporine [R].

This drug increases the sedative effects of nervous system depressants such as barbiturates, alcohol, and narcotic painkillers [R].

It can increase the potential for weight gain and swelling in patients receiving thiazolidinedione hypoglycemic agents [R].

There were no adverse reactions reported when pregabalin was used simultaneously with these anti-epileptic drugs [R]:

  • Carbamazepine
  • Lamotrigine
  • Phenobarbital
  • Phenytoin
  • Topiramate
  • Valproate

There were no adverse effects recorded with simultaneous use of [R]:

  • Lorazepam
  • Oral Oxycodone
  • Oral contraceptives
  • Alcohol

Is Pregabalin a Narcotic?

Pregabalin is a schedule V controlled drug and not a narcotic [R, R].

It is not active at receptor sites linked with drugs of abuse [R].

However, it does decrease excitation in the nervous system and it can lead to limited physical or psychological dependence [R].

In a study of sedative/hypnotic drugs, pregabalin received ratings of “good drug effect,” “high,” and “liking” similar to diazepam by recreational users [R].

In controlled clinical studies with over 5,500 patients, 4% of pregabalin-treated patients and 1% of placebo-treated patients reported euphoria [R].

A systematic review concluded that there is a significant risk of this drug being abused [R, R].

The main population at risk for the addiction of gabapentinoids are patients with other current or past substance use disorders, mostly opioid and multi-drug users [R].

Pure overdoses of pregabalin are relatively safe but can become lethal when mixed with other psychoactive drugs, especially opioids and sedatives [R].

Pregabalin vs. Gabapentin and Mirogabalin

In preclinical trials of anticonvulsant activity, pregabalin was 3 to 10 times more effective than gabapentin [R].

Pregabalin is effective for the treatment of generalized anxiety disorder while gabapentin is more effective for the treatment of restless legs syndrome [R].

Pregabalin is more cost-effective and requires fewer doses than gabapentin, and it is effective in patients who have previously failed to respond to gabapentin [R].

Mirogabalin, a new gabapentinoid, is being investigated for the treatment of neuropathic pain in the limbs and fibromyalgia. It is showing promising results in patients with diabetic peripheral neuropathy [R].

Mirogabalin had superior analgesic effects with a wider safety margin relative to pregabalin in rats [R].

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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4 COMMENTS

  • Kathy Burns

    I took this crap and gained 70 pounds in one month. BE AWARE! I went from a size 10 to a size 14 in one month. Every time I see the commercials I get angry.

  • Jeffrey K

    Carol, while I’ve heard that Gabapentin can cause cognitive impairment, especially at higher doses, I can’t find any evidence that either drug has anticholinergic properties. One study tested for anticholinergic effects and didn’t find any.

    That obviously doesn’t mean the drugs are “safe,” or that we won’t discover anticholinergic effects, but for now, they don’t seem to have direct action on ACh receptors.

  • carol close

    Pregabalin reduces the release of several excitatory neurotransmitters, including glutamate, substance P, acetylcholine and norepinephrine….. 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. So, beware as anticholinergics cause dementia.

  • carol close

    This is on the list of drugs that are anticholinergic and cause dementia and increase brain atrophy. Lyrica /Pregablin and Gabapentin cause memory problems that may be irreversible because they are anticholinergic.
    https://www.ncbi.nlm.nih.gov/pubmed/28436193 Association between using medications with anticholinergic properties and short-term cognitive decline among older men: A retrospective cohort study in Taiwan.“The use of anticholinergic drugs has been strongly associated with adverse health outcomes, including cognitive impairment, dementia, falls, functional decline, hospitalization and mortality, especially in older adults.”
    Health professionals may not realize that the medicine they are prescribing could affect the brain. In our opinion medical students are not given enough information on this crucial topic. And prescribers do not have easy access to a list of drugs that affect the action of acetylcholine in the brain.

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