Pregabalin vs Gabapentin: What’s the Difference?

Pregabalin vs Gabapentin: Overview

Pregabalin and gabapentin are prescription drugs that are used to treat similar conditions. But these two drugs are not the same. Please continue reading to learn about the differences between pregabalin (Lyrica) vs gabapentin (Neurontin).

Definition and Classification

Pregabalin and gabapentin are antiepileptic drugs called gabapentinoids. They are commonly prescribed to treat seizures and nerve pain caused by shingles. There are many similarities between the two, including similar-sounding generic names. It is not uncommon for people to switch from gabapentin to pregabalin and vice versa. However, they are not interchangeable, and the switching/conversion process should only be done with a healthcare professional’s instructions and guidance.

Common Uses in Neuropathic Pain

Pregabalin and gabapentin are commonly used to treat neuropathic (nerve-related) pain, such as:

Postherpetic neuralgia (PHN) related to shingles.
Diabetic peripheral neuropathy caused by nerve damage in people with diabetes.
Chronic sciatica (leg pain due to irritation of the sciatic nerve).
Trigeminal neuralgia (intense, electric-shock-like pain on one side of the face).
Chronic neuropathic pain related to spinal cord injuries.

Note: Some of these are off-label uses of pregabalin and gabapentin.

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Key Differences: Pregabalin (Lyrica) vs. Gabapentin (Neurontin)

Generic Drug and Brand Names

The generic drug gabapentin is available under the brand names Neurontin, Gralise, and Horizant. Gralise and Horizant are the extended-release formulations of gabapentin.
The generic drug pregabalin is available under the brand names Lyrica and Lyrica CR (extended-release pregabalin).

Chemical Structure

Gabapentin: C₉H₁₇NO₂
Pregabalin: C₈H₁₇NO₂

Mechanism of Action

Pregabalin and gabapentin are structurally related to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Gabapentin, pregabalin, and GABA all modulate voltage-gated calcium channels.

The mechanism of action of gabapentinoids like gabapentin and pregabalin in seizure treatment and pain management is not fully understood. However, scientists believe these drugs may work by decreasing excitatory neurotransmitter release.

Pharmacokinetics and Pharmacodynamics

Studies by Brockbader, Wesche, and others have found there are differences in the pharmacokinetics (the journey of the drug through your body) pharmacodynamics (how the drug works on your body) of pregabalin (Lyrica) vs gabapentin (Neurontin).

Pregabalin is absorbed more quickly and starts working faster than gabapentin. Peak concentration of pregabalin is reached within 1 hour whereas peak concentration of gabapentin occurs 3-4 hours after taking a dose.
Pregabalin has a more predictable dose response curve compared to gabapentin. The blood concentration of pregabalin increases linearly with increasing dosages. The blood concentration of gabapentin does not increase in direct proportion to increasing doses.
Bioavailability of pregabalin is 90% regardless of dose. Bioavailability of gabapentin decreases from 60% to 33% with an increase in dose from 900 mg per day to 3600 mg per day.

Metabolism and Elimination

Both pregabalin and gabapentin are eliminated from the body by the kidneys. However, the renal clearance of pregabalin is less than the glomerular filtration rate (GFR) whereas that of gabapentin is similar to the GFR. The GFR shows how effective your kidneys are at filtering out substances. This indicates that some pregabalin is reabsorbed in the renal tubules.

FDA Approval

Gabapentin was first approved by the U.S. Food and Drug Administration (FDA) in 1993.
Pregabalin is a newer drug. It first received FDA approval in 2004.

FDA-Approved Uses

Gabapentin therapy is FDA-approved for:

Partial onset seizures
Painful neuropathy after a shingles attack
Restless leg syndrome (Horizant brand)

Pregabalin is FDA-approved to treat:

Partial seizures
Neuropathic pain after shingles
Diabetic neuropathy
Neuropathic pain from spinal cord injury
Fibromyalgia

Note: Most of the FDA-approved indications of pregabalin are off-label uses of gabapentin.

Common Uses

Gabapentin Uses

Gabapentin is used as an adjunctive therapy (add-on treatment) for partial-onset seizures for adults and children who are 3 years and older. It is also approved as a pain med for postherpetic neuralgia (nerve pain after an outbreak of herpes zoster infection or shingles).

The brand name drug Horizant contains gabapentin enacarbil. It is approved to treat moderate to severe restless legs syndrome and postherpetic neuralgia. Restless legs syndrome is a condition in which there is a strong urge to move the legs, which can result in sleep disturbances.

In addition, gabapentin is used off-label to treat conditions such as diabetic peripheral neuropathy, chronic neuropathic pain, drug and alcohol withdrawal seizures, premenstrual syndrome, bipolar disorder, post-traumatic stress disorder (PTSD), and various anxiety disorders.

Pregabalin Uses

Pregabalin is used to treat partial-onset seizures for adults and children who are as young as 1 month old. It is also approved for pain control in people with postherpetic neuralgia after a shingles outbreak, peripheral neuropathic pain related to diabetic neuropathy, neuropathic pain related to spinal cord injury, and fibromyalgia.

Pregabalin is approved by the European Medicines Agency to treat generalized anxiety disorder (GAD). However, in the U.S., pregabalin is not FDA-approved for anxiety disorders. Nonetheless, pregabalin is used off-label to treat generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder (OCD).

Controlled Status

Pregabalin is a Schedule V (5) federally controlled substance, while gabapentin is not considered a controlled substance by the Drug Enforcement Agency (DEA). In fact, gabapentin is only a Schedule V (5)controlled substance only in certain states.

Pain Management: Clinical Studies and Results

Studies published in medical journals indicate that both Lyrica (pregabalin) and Neurontin (gabapentin) are effective in treating nerve pain. A systematic review of clinical trials (controlled trials) does not show significant differences between them. One might work better for you than the other. You may have fewer adverse events on one of these medications. Other factors, such as cost or insurance coverage, might affect the choice of medication. Your doctor will help you choose the best medicine for your condition.

There are mixed results from studies comparing pregabalin (Lyrica) vs gabapentin (Neurontin) for chronic neuropathic pain. Some study results are as follows:

A cohort study investigated the outcomes of substituting gabapentin with pregabalin in patients with peripheral nephropathy. The study found that participants had additional pain relief with a reduction in pain scores by approximately 25% at 6 or 12 months after switching from gabapentin to pregabalin. This study included participants who responded to gabapentin initially as well as those who didn’t.
A meta-analysis found that pregabalin may have a better overall effect than gabapentin for postherpetic neuralgia, but gabapentin causes fewer adverse reactions and has a better safety profile.
A head-to-head trial between pregabalin (Lyrica) vs gabapentin (Neurontin) in patients with chronic sciatica found that gabapentin was superior to pregabalin in reducing leg pain with fewer side effects.

Is Pregabalin Good For Severe Pain?

Pregabalin may be good for severe nerve pain, but other medications may work better for other types of pain, such as severe musculoskeletal pain. Opioid pain relievers (oxycodone, hydrocodone, tramadol, and others) are some of the strongest drugs available for short-term, severe pain control.

Effectiveness: Anxiety, Insomnia, and Fatigue

A placebo-controlled trial found that both gabapentin and pregabalin therapy had a greater response to treatment compared to placebo in patients with fibromyalgia.
Gabapentin is sometimes used to treat anxiety, but there are no randomized controlled trials evaluating the efficacy of gabapentin in generalized anxiety disorder (GAD).

Dose Equivalence: Gabapentin to Pregabalin Calculations

How Much Gabapentin Is Equivalent To Pregabalin?

There is no direct dose conversion between gabapentin and pregabalin for the initial dose, maintenance dose, or maximum dose. So, for example, if you are on a 50 mg pregabalin dose, only a healthcare professional can tell you the equivalent gabapentin dose.

Which is Stronger: Pregabalin or Gabapentin?

Pregabalin is approximately 2.5 times stronger than gabapentin based on blood concentrations. However, as noted, there is no direct dose conversion ratio between the two. Your healthcare provider will decide the appropriate dose if you are switching between these two medications.

Is Pregabalin Equivalent to Morphine?

Pregabalin is not equivalent to morphine. While pregabalin is an anticonvulsant drug that is used to treat nerve pain, morphine is an opioid drug (narcotic analgesic) prescribed for severe pain that does not respond to other pain medications. Head-to-head comparisons between morphine vs pregabalin in patients with neuropathic pain have shown that over 92% of patients found morphine monotherapy effective or very effective for pain reduction compared to only about 19% of patients who found pregabalin monotherapy effective. Therefore, morphine is undoubtedly a stronger painkiller than pregabalin, but it is not the first-line treatment for nerve pain

Administration: Pregabalin vs. Gabapentin

Dosage Forms and Strengths

Gabapentin is available as a capsule, tablet, oral solution, and extended-release tablet.

Brand name Neurontin
- Oral capsule (100 mg, 300 mg, 400 mg)
- Oral tablet (600 mg, 800 mg)
- Oral solution (50 mg/mL)

Brand name Gralise
- Oral tablet (300 mg, 600 mg)

Brand name Horizant (gabapentin enacarbil)
- Extended-release tablet (300 mg, 600 mg)

Pregabalin is available as a capsule, oral solution, and extended-release tablet.

Brand name Lyrica
- Oral capsule (25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg)
- Oral solution (20 mg/mL)

Brand name Lyrica CR
- Extended-release tablet (82.5 mg, 165 mg, 330 mg)

Dosage Recommendations

The usual starting dose of gabapentin in adults with postherpetic neuralgia is a single 300-mg dose on day 1, two 300-mg doses (600 mg total) on day 2, and three 300-mg doses (900 mg total) from day 3 onwards. The maximum dose of gabapentin is 1800 mg per day in three divided doses.

The usual starting dose of pregabalin is 50 mg three times a day or 75 mg two times a day (total daily dose of 150 mg) for postherpetic neuralgia and nerve pain related to diabetic peripheral neuropathy. The maximum recommended dose of pregabalin is 300 mg per day.

Patient Considerations: Age, Weight, and Comorbidities

Gabapentin

You can take gabapentin with or without food.
If you break the 600-mg or 800-mg tablet of gabapentin along the score line, take the unused half-tablet at your next dose. Do not store half-tablets for several days.
If you have compromised kidney function or are undergoing hemodialysis, your doctor will adjust your gabapentin dose.
While reducing your gabapentin dose or coming off the medicine, follow your doctor’s dosing instructions to reduce the dose slowly over 1 week or longer to prevent withdrawal symptoms.

Pregabalin

You can take pregabalin with or without food.
If you have decreased renal function, your doctor will adjust your pregabalin dose.
While reducing your pregabalin dose or coming off the medicine, your doctor will tell you how to lower the dose gradually over 1 week or more to prevent withdrawal symptoms.
The dosage of pregabalin in pediatric patients with partial-onset seizures depends on the child’s age and body weight.

Best Practices: Can You Switch From Pregabalin to Gabapentin?

Yes, you can switch from pregabalin to gabapentin and vice versa. However, you should only do this under the supervision and guidance of a healthcare provider. Keep in mind that these two medications are not interchangeable.

Also, make sure you talk to your doctor before stopping either of these antiepileptic drugs. Stopping pregabalin or gabapentin suddenly can put you at an increased risk of serious withdrawal symptoms. Your provider will tell you how to slowly stop taking one drug and start taking the other drug while switching between gabapentin and pregabalin.

Side Effects: Pregabalin vs Gabapentin

Comparison of Common Side Effects

The most common side effects of Lyrica include dizziness, drowsiness, headache, dry mouth, blurred vision, constipation, peripheral edema (swelling in the limbs), weight gain, and indigestion.
The most common side effects of gabapentin are drowsiness, dizziness, shaking, diarrhea, and weakness.

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Severe Adverse Effects

Lyrica (pregabalin) has been linked to serious adverse effects such as rhabdomyolysis, while gabapentin has not. Signs and symptoms of rhabdomyolysis may include fever, muscle pain, muscle tenderness, muscle soreness, and muscle weakness.

Serious Risks and Safety Concerns

Possible serious risks of taking gabapentin include:

Suicidal thoughts or behavior.
Neuropsychiatric adverse events in pediatric patients, including behavioral problems, aggression, problems with concentration, restlessness, and hyperactivity.
Worsening seizure control if the drug is withdrawn suddenly or too quickly.
Risk of tumors called pancreatic acinar adenocarcinomas (based on animal studies).
Sudden and unexpected death in people with seizure disorders.

Possible serious risks of taking pregabalin include:

Angioedema (swelling of the face, lips, tongue, and throat).
Hypersensitivity (allergic) reactions (skin rash, hives, itching, blisters, difficulty breathing).
Increased risk of suicidal thoughts or behavior.
Respiratory depression (slowed or stopped breathing).
Withdrawal symptoms, including increased seizure frequency, if the drug is rapidly or abruptly discontinued.
Risk of tumors called hemangiosarcoma (based on animal studies).
Elevation in creatine kinase enzyme and risk of rhabdomyolysis (a serious complication in which there is muscle breakdown).
Decreased platelet count.
Changes in heart rhythm with prolongation of the PR interval.

Drug Interactions and Contraindications

Gabapentin can interact with the following medications

Antidepressants and anxiety medications
Antihistamines
Anti-seizure medications
Psychiatric medications
Medications that cause dizziness or drowsiness
Nonsteroidal anti-inflammatory drugs such as naproxen (Naprosyn, Anaprox, Aleve)
Opioid pain medications such as morphine, hydrocodone, and oxycodone
Sedatives, sleeping pills, and tranquilizers

Pregabalin can interact with:

Antidepressants
Certain anti-anxiety medications
Antihistamines
Psychiatric medications for mental illness
Anti-seizure medications
Blood pressure medications called angiotensin-converting enzyme (ACE) inhibitors
Certain oral diabetes medications
Opioid pain medications such as morphine, hydrocodone, and oxycodone
Sedatives, sleeping pills, and tranquilizers

Contraindications and Precautions

Gabapentin may not be safe for people with:

Lung disease
Kidney disease

Pregabalin may not be safe for people with:

Drug or alcohol abuse
Swelling of the face or mouth
Vision problems
Low platelets or bleeding problems
Heart failure or heart disease
Lung disease
Kidney disease

Can You Get Addicted to Pregabalin or Gabapentin?

There are reports of gabapentin abuse for its euphoric effects. Gabapentin is also sometimes misused to manage opioid withdrawal symptoms or to increase the effects of methadone.

Pregabalin is a Schedule V controlled substance. It has a calming effect which can be described as a gentle high. Pregabalin may not be safe for people with a prior history of alcohol abuse, street drug abuse, or prescription drug misuse.

Similarities Between Pregabalin and Gabapentin

Uses: Both pregabalin and gabapentin are prescription medications approved to treat seizures and neuropathic pain (postherpetic neuralgia after a shingles outbreak).
Chemical Structure and Pharmacokinetics: Gabapentin and pregabalin are antiepileptic medications that are structurally similar to the brain chemical GABA (gamma-aminobutyric acid). They also have similar pharmacokinetic properties.
Mechanism of Action: Both Lyrica and gabapentin work by binding to voltage-gated calcium channels in nerve cells in the central nervous system.
Elimination: Both drugs undergo renal excretion, i.e., they are removed from the body by the kidneys. The half-life of both medicines is around 6 hours. This means it takes approximately 6 hours for the concentration of the drug to be reduced to half of the original amount.
Dosing: Gabapentin and pregabalin are typically dosed 2-3 times a day. However, Gralise is a once-a-day dosing medication.
Drug Interactions: Both medicines have similar drug interactions, including with antihistamines, antidepressants, medications prescribed for mental illnesses and seizure control, opioid pain medications, sleeping pills, sedatives, and tranquilizers.
Side Effects: Both gabapentin and pregabalin cause similar adverse effects, such as dizziness, drowsiness, somnolence, blurred vision, dry mouth, nausea, and vomiting. Rarely, these two medications can cause serious adverse events, including allergic reactions with skin rash, hives, itching, swelling of the face, tongue, and lips, respiratory depression, and difficulty breathing. Neurontin (gabapentin) & Lyrica (pregabalin) can both increase the risk of suicidal ideation.
Withdrawal Symptoms: Abrupt discontinuation of both Lyrica and gabapentin can cause withdrawal symptoms.