Pregabalin (Lyrica) is approved for neuropathic pain in diabetes, spinal cord injury, post-herpetic pain, and fibromyalgia. It is also used off-label for various conditions such as pruritus, anxiety, and restless leg syndrome. Find out more about its uses, mechanisms, and side effects.
What is Pregabalin (Lyrica)?
Pregabalin (brand name Lyrica) is a medication that is FDA-approved to treat various forms of nerve pain. It is also used in combination with other medications to treat certain types of seizures [1].
In addition, pregabalin is used off-label for several other pain-related conditions as well as for anxiety and restless leg syndrome.
Mechanism of Action
Pregabalin is classified as a gabapentinoid, similar to GABA and gabapentin [2].
According to research, pregabalin primarily works by inhibiting certain calcium channels in the neurons of the brain and spine. This reduces the excitation of nerves, which can potentially produce pain-reducing, anti-seizure, and anti-anxiety effects [3].
There is also evidence that pregabalin increases the density of GABA transporter proteins and increases the rate of GABA transport, which may also have biological effects [4].
Other possible mechanisms of pregabalin include decreasing levels of glutamate, substance P, and inhibiting the activity of NMDA receptors [5, 6, 7].
Uses of Pregabalin (Lyrica)
FDA-Approved Uses
Neuropathic Pain
Neuropathic pain occurs when the nerves in the body become damaged, which can result in chronic pain. There are many factors that can cause neuropathic pain, such as injury, cancer, and certain infections [8].
Pregabalin is approved to treat neuropathic pain that is caused by:
- Diabetic Peripheral Neuropathy
- Spinal Cord Injury
- Shingles
In the sections below, we’ll go over the role of pregabalin for each of these types of neuropathic pain.
Diabetic Peripheral Neuropathy
Diabetic peripheral neuropathy is a form of nerve damage that can occur in diabetic patients, due to injury to the blood vessels. Research suggests that pregabalin is effective for this type of nerve pain [9, 10].
For example, a systematic review of 19 clinical trials including 7,003 participants found that pregabalin may reduce pain associated with diabetic neuropathy [11].
However, the researchers suggest that only a minority of patients will see a significant benefit. They also conclude that some patients will experience a moderate benefit and that the majority of patients will see little to no benefit [11].
A different review of 9 clinical trials including 2,399 patients found that pregabalin may also reduce pain-related sleep disturbances in patients with diabetic neuropathy [12].
Spinal Cord Injury
Injuries to the spinal cord can also lead to neuropathic pain.
A randomized placebo-controlled trial of 220 patients with pain due to spinal cord injury found that pregabalin may reduce pain and pain-related sleep disturbances. Researchers noted that a significant reduction of pain occurred as early as the first week of treatment [13].
A review of 5 clinical trials including 223 patients with spinal cord injury also shows that pregabalin may be effective for neuropathic pain. Results of the review suggest that pregabalin may be more effective for pain relief than gabapentin, although pregabalin was associated with more side effects [14].
Shingles
Shingles (herpes zoster) is caused by the varicella-zoster virus, which is the same virus that causes chickenpox. Shingles can also cause damage to the nerves, causing a type of neuropathic pain called postherpetic neuralgia [15].
In a systematic review of 19 studies including 7,003 participants, pregabalin was found to be potentially effective for shingles-related neuropathic pain, but only a minority of patients experienced a substantial benefit. The review also found that 18-28% of patients taking pregabalin discontinued the medication due to side effects [11].
Another review of 9 clinical trials with data from 2,399 patients suggests that pregabalin may also reduce sleep disturbances due to shingles-related neuropathic pain [12].
Fibromyalgia
Fibromyalgia is a disorder that causes chronic widespread pain. Symptoms can include fatigue, poor quality of sleep (unrefreshing, nonrestorative sleep), depression, anxiety, and muscle and joint stiffness [16].
Pregabalin was the first medication approved by the FDA for the management of fibromyalgia. Research shows that pregabalin may not only provide pain relief but also improves functional ability and quality of life [17].
A meta-analysis of 5 clinical trials including 3,808 patients found that pregabalin may reduce pain and sleep problems associated with fibromyalgia. However, the researchers point out that only a minority of patients achieved moderate or substantial pain relief [18].
In a systematic review of 8 studies with 3,283 participants, pregabalin was shown to be effective for fibromyalgia pain over 12 to 26 weeks. However, the proportion of people that experienced substantial pain relief with pregabalin was only 10% more than placebo [19].
Seizures
Pregabalin is also approved as an add-on medication for the treatment of partial-onset seizures, a common type of seizure that originates in one side of the brain. Pregabalin is typically added on to other seizure medications for conditions that are resistant to conventional treatment [20].
A systematic review of 9 clinical trials of 3,327 subjects found that pregabalin (as an add-on drug) may be effective for reducing seizures by 50% or more. However, researchers note that all the included trials had short durations and longer-term trials are needed [21].
Off-Label Uses
Pregabalin is used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed pregabalin, always take the medication as directed by your doctor.
Chemotherapy-Induced Neuropathy
Chemotherapy treatment can often cause damage to the nerves, potentially resulting in chemotherapy-induced neuropathy.
In a study of 23 cancer patients with chemotherapy-induced neuropathy, pregabalin improved pain scores in about half of the patients [22].
However, a randomized placebo-controlled trial of 26 patients with chemotherapy-induced neuropathy found that pregabalin did not reduce average daily pain [23].
Pruritus (Itching)
There’s some evidence that pregabalin may be effective for certain kinds of pruritus (itching).
For example, a randomized placebo-controlled trial looked at 80 patients with pruritus due to burns. Researchers found that pregabalin may relieve itching and neuropathic pain [24, 25].
Pregabalin is also sometimes used for uremic pruritus, a type of itch that can occur in people with chronic kidney disease. A systematic review of 44 clinical trials examined the effectiveness of various treatments for this condition and concluded the evidence supporting the use of pregabalin is weak [26].
Postoperative Pain
Pregabalin is sometimes used to reduce pain after surgery. However, there is conflicting evidence on how effective pregabalin is for this purpose.
A systematic review of 97 clinical trials with 7,201 patients suggests that pregabalin has a minimal effect on acute pain after surgery [27].
Another systematic review of 18 studies including 2,485 patients found no difference between pregabalin and placebo for chronic pain after surgery [28].
The effectiveness of pregabalin may depend on the specific type of surgery. A systematic review of 74 clinical trials suggests that pregabalin may reduce pain and the need for opioid drugs in the following types of surgery [29]:
- Cardiothoracic
- Eyes, nose, and throat
- Gynecologic
- Laparoscopic cholecystectomy
- Orthopedic
- Spine
Other systematic reviews also suggest that pregabalin may be effective for the following types of surgery:
Chronic Back Pain
There’s evidence that pregabalin may be effective as an add-on medicine for chronic back pain.
For example, a randomized double-blind study of 36 patients suggests that the combination of celecoxib (an NSAID drug) and pregabalin is more effective than either drug alone for chronic low-back pain [33].
However, a systematic review of 8 clinical trials found that the evidence is limited for the treatment of chronic lower back pain with pregabalin. The researchers caution against the use of pregabalin due to the lack of demonstrated benefit and the risk of side effects [34].
Anxiety
Pregabalin may help improve certain types of anxiety.
According to a systematic review of 8 clinical trials including 2,299 patients, pregabalin may improve symptoms of generalized anxiety disorder. The results of the study also suggest that pregabalin may be as effective as benzodiazepines, a class of drugs commonly used for anxiety [35].
A different review of 3 clinical trials found that pregabalin may also be effective for treating social anxiety disorder [36].
Restless Leg Syndrome
Restless legs syndrome (RLS) is a nerve disorder in which the patient has an uncontrollable urge to move their legs [37].
In a randomized placebo-controlled trial of 137 patients with RLS, pregabalin reduced symptoms after 6 weeks of treatment [38].
Another 12-week double-blind randomized controlled trial with 58 patients demonstrated that pregabalin may relieve symptoms of restless leg syndrome and improve sleep [39].
According to guidelines published by the European Federation of Neurological Societies, pregabalin is effective for the short-term treatment of RLS, but it is not recommended for long-term treatment [40].
Safety of Pregabalin
Side Effects
Side effects can be common when taking pregabalin. If any side effects persist or worsen, let your doctor know. This list does not cover all possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.
Some common side effects include [41]:
- Dizziness
- Drowsiness
- Dry mouth
- Blurred vision
- Weight gain
- Difficulty concentrating
- Constipation
Some rare, but serious side effects include [41]:
- Unusual bleeding or bruising
- Muscle weakness or pain
- Suicidal thoughts or actions
- Trouble breathing
Warnings
1) Suicide Risk
Pregabalin is associated with a higher risk of suicidal thinking and behavior in a small number of people. Those taking pregabalin should be monitored and any changes in behavior should be reported to a doctor [1].
2) Withdrawal Symptoms
Talk to your doctor first before stopping pregabalin. This medication may cause side effects if abruptly stopped, such as headaches, nausea, and diarrhea. Stopping pregabalin suddenly may also increase the risk of seizures in those with epilepsy. A doctor will gradually lower the dose if pregabalin needs to be discontinued [1].
3) Swelling
Pregabalin may cause swelling of the throat, head, and neck, which is referred to as angioedema. This swelling is potentially life-threatening as it can make breathing difficult. Seek immediate help if you suspect that you are experiencing this type of swelling [1].
Contraindications
Pregabalin is contraindicated in patients with known hypersensitivity to pregabalin or any of its components [41].
Pregnancy and Breastfeeding
Some research suggests that pregabalin may be associated with birth defects, although strong clinical evidence is lacking. Pregabalin should only be used during pregnancy if a doctor determines that the benefits outweigh risks [42].
Small amounts of pregabalin are excreted in breast milk. Again, a doctor will decide if pregabalin can be used during breastfeeding [42].
If you are taking pregabalin and are pregnant or planning to become pregnant, let your doctor know.
Drug Interactions
The following drugs have been reported to interact with pregabalin. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions:
- Buprenorphine
- Propoxyphene
- Sodium oxybate
Dosage
Always take pregabalin as directed by a doctor and do not discontinue the medication abruptly.
Pregabalin is available as 25, 50, 75, 100, 150, 200, 225, and 300 mg capsules. An oral solution is also available for those with difficulty swallowing.
For all FDA-approved uses, dosing typically should begin at 150 mg per day, which can be gradually increased until effective. Doses are usually taken in 2-3 divided doses per day.
The maximum dose is 300 – 600 mg per day, depending on the condition.
