While gabapentin (Neurontin) and pregabalin (Lyrica) share many similarities, there are a few things that set them apart. We’ll highlight seven key differences between these medications below.
1. Pregabalin is FDA approved for more uses than gabapentin, but both are often used off-label
Pregabalin and gabapentin are both FDA approved as an add-on treatment for partial-onset seizures. But pregabalin is approved for adults and children as young as 1 month old, whereas gabapentin is approved for adults and children who are at least 3 years old.
Pregabalin and gabapentin are also approved for nerve pain from shingles (postherpetic neuralgia). Pregabalin has a few more approved uses, such as:
- Fibromyalgia
- Nerve pain from diabetes (diabetic neuropathy)
- Nerve pain from spinal cord injuries
Even though gabapentin isn’t approved for these reasons, it’s still used for conditions such as fibromyalgia and diabetic neuropathy. In fact, gabapentin is often a first-choice medication for diabetic neuropathy.
Off-label uses
Your healthcare provider may suggest taking pregabalin or gabapentin for an “off-label” use. This means the FDA has not approved pregabalin or gabapentin to treat certain conditions, but your provider might prescribe it anyway. Some of these conditions include:
- Other types of nerve pain
- Menopause-related symptoms
- Muscle and bone-related pain, like back pain
- Anxiety
- Headache
- Restless leg syndrome
- Alcohol use disorder
2. Pregabalin and gabapentin work in similar ways, but pregabalin is absorbed more quickly and fully
Pregabalin and gabapentin are known as gabapentinoids. They’re structurally similar to a chemical called GABA. GABA is an important “inhibitory” neurotransmitter (chemical messenger) in the body. This means it decreases the activation of your nerve cells, and has a calming effect.
How these medications work to treat conditions like nerve pain and seizures isn’t fully understood. Even though pregabalin and gabapentin are structurally similar to GABA, they don’t have any effect on GABA receptors (binding sites). And they don’t increase levels of GABA in the body. Instead, they likely work by decreasing the release of “excitatory” neurotransmitters in the body. Excitatory neurotransmitters activate your nerve cells. Decreasing this activation may help treat conditions such as seizures and nerve pain.
Both medications stay in your blood for about the same amount of time. But pregabalin is more quickly absorbed by the body than gabapentin. It reaches peak blood levels within about 1 hour, compared to 3 hours or more for gabapentin. Each pregabalin dose is also more fully absorbed than gabapentin. This means that as your pregabalin dose increases, you’ll have higher levels of pregabalin in the blood. This isn’t necessarily true with gabapentin.
Converting from Gabapentin to Pregabalin
For clinicians who wish to convert patients from gabapentin to pregabalin, there are a few studies that reviewed such a conversion.
One cohort study reviewed the utility of switching patients with neuropathic pain due to peripheral neuropathy from gabapentin to pregabalin.10 The study followed patients who were switched from gabapentin to pregabalin and then compared them to those who stayed on gabapentin. The authors also stratified the pregabalin group further into those who responded well or poorly to gabapentin, with gabapentin stopped after the nighttime dose and pregabalin started the following morning.
Dosages were switched using the following algorithm:
- Gabapentin ≤900 mg/day → pregabalin 150mg/day
- Gabapentin 901 mg/day to 1500 mg/day → pregabalin 225 mg/day
- Gabapentin 1501 mg/day 2100 mg/day → pregabalin 300 mg/day
- Gabapentin 2101 mg/day 2700 mg/day → pregabalin 450 mg/day
- Gabapentin >2700 mg/day → pregabalin 600 mg/day
This rapid change was generally well tolerated by patients.
The authors found that those who responded well to gabapentin and those who did not showed additional benefit with decreased pain when they were switched to pregabalin. Patients taking pregabalin also had improved pain control compared with those who remained on gabapentin.
Switching to pregabalin resulted in improved pain relief and also fewer adverse events. This was particularly true for patients who previously responded to gabapentin.
Patients who experienced adverse events with gabapentin were more likely to also experience adverse events with pregabalin. These patients were also more likely to discontinue use of pregabalin than those who responded well to both gabapentin and pregabalin.
Another small trial compared the degree of pain relief with gabapentin to pregabalin in patients with postherpetic neuralgia in order to more closely determine equivalent dosing between the 2 medications.
Patients were switched from gabapentin to pregabalin using one-sixth the dose of gabapentin with unchanged dosage frequency. After switching medications, patients reported similar pain relief and side effects, with the exception of an increased incidence of peripheral edema in the pregabalin group.
The authors concluded that the analgesic effect of pregabalin was about 6 times that of gabapentin.
Other studies have looked at methods for converting gabapentin to pregabalin. One such trial used population pharmacokinetic models to examine 2 possible scenarios for converting gabapentin to pregabalin, using a ratio of 6:1 gabapentin to pregabalin.
The first scenario involved discontinuing gabapentin and immediately starting pregabalin at the next scheduled dosing period. The other option included a gradual transition from gabapentin to pregabalin.
In this second scenario, the gabapentin dose was decreased by 50%, and 50% of the desired pregabalin dose was given concurrently for 4 days. After this time, gabapentin was discontinued and pregabalin was increased to full desired dose.
The model looked at transitioning patients from gabapentin to pregabalin at various doses, including:
- Gabapentin 900 mg/day → pregabalin 150 mg/day
- Gabapentin 1800 mg/day → pregabalin 300 mg/day
- Gabapentin 3600 mg/day → pregabalin 600 mg/day
Both scenarios were quick and seamless, so the authors concluded that either technique could be an effective method to switch patients between the medications.
3. Pregabalin and gabapentin come in different forms
Pregabalin and gabapentin both come as oral capsules and are available as a liquid solution. Gabapentin also comes as an oral tablet. Pregabalin is taken 2 to 3 times a day and gabapentin is usually taken 3 times a day. If you have kidney problems, your pregabalin or gabapentin dose may need to be lowered. This is because both medications are cleared from the body by the kidneys.
Extended-release (ER) formulations are available for both medications. The ER version of pregabalin is a tablet called pregabalin ER (Lyrica CR). It’s available as a brand-name and generic medication to treat postherpetic neuralgia and diabetic neuropathy.
Gabapentin has two brand-only ER formulations: Gralise and Horizant. Both are tablets approved to treat postherpetic neuralgia. Horizant is also approved for restless leg syndrome.
Pregabalin ER and Gralise are taken once daily. Horizant is taken once daily for restless leg syndrome, but may be taken twice daily for postherpetic neuralgia.
4. Pregabalin is considered a controlled substance by the federal government, but gabapentin is only controlled in some states
The federal Drug Enforcement Agency (DEA) lists pregabalin as a schedule 5 controlled substance. This means it’s a controlled substance in every state. Gabapentin, however, isn’t considered a controlled substance by the DEA. It’s only considered a Schedule 5 controlled substance in some states.
When a medication is listed as a controlled substance, it means it has a higher risk for dependence and misuse. Schedule 5 medications are considered to pose the lowest risk among other controlled substances. For instance, the chance of dependence or misuse is lower than it is with an opioid such as oxycodone, which is a Schedule 2 drug. But the risk is then higher with gabapentin or pregabalin than with non-controlled substances, such as blood pressure medications.
If you struggle with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.
5. One may be more effective than the other in some situations
Pregabalin and gabapentin treat similar health conditions. But in some cases, one medication has been more extensively studied than the other. That may be why it’s recommended. In other cases, one medication may work better than another.
For example, when used for menopause symptoms, health experts only recommend gabapentin as a treatment option for hot flashes or night sweats. This is mostly due to a lack of research on pregabalin for this use.
Talk to your healthcare provider if you’re wondering whether pregabalin versus gabapentin is a better choice for you. They’ll consider your medical history, personal preferences, and expected out-of-pocket costs of these medications.
6. Pregabalin and gabapentin have similar side effects, but there are a few differences
Side effects are generally similar for pregabalin and gabapentin. But there are a few differences to be aware of.
Common side effects
Dizziness and drowsiness are the most common side effects of pregabalin and gabapentin. It may be less of an issue with Gralise and pregabalin ER. Other possible side effects include:
- Fluid buildup in the arms and legs (edema)
- Eye problems
- Dry mouth
One side effect that’s more common with pregabalin is weight gain. This side effect doesn’t appear to be linked to fluid buildup, but it’s something to pay attention to if you’re starting pregabalin. Weight gain doesn’t seem to be as common with gabapentin.
Serious side effects
Though rare, pregabalin and gabapentin have more serious risks, as well. Examples include:
- Suicidal thoughts or actions: Pregabalin and gabapentin can increase the risk of suicidal thoughts or actions at any point during treatment. Pregabalin may be more likely to cause suicidal thoughts.
- Heart problems: A 2022 study found an increased risk for heart problems with both gabapentin and pregabalin. In the study, gabapentin was linked to more heart-related risks in the short-term.
- Breathing problems: It’s wise to avoid taking pregabalin or gabapentin with other medications that slow down brain activity. Examples include opioids, benzodiazepines, and antihistamines. Alcohol can also lead to this interaction.
- Withdrawal: Stopping pregabalin or gabapentin suddenly can cause withdrawal symptoms, including nausea, agitation, and sweating. If you take pregabalin or gabapentin for seizures, stopping abruptly could cause seizures to return.
- Severe allergic reactions: Gabapentin has been linked with a rare allergic reaction called DRESS (drug reaction with eosinophilia and systemic symptoms). And both medications may cause angioedema in rare instances. Get medical help right away if you have a fever or rash in the months after starting gabapentin.
If you or a loved one experience a change in behavior after starting either medication, call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
7. Gabapentin is more affordable than pregabalin
Pregabalin and gabapentin are available as brand-name medications. But you can also find them as lower-cost generics.
Gabapentin is generally more affordable than pregabalin. But GoodRx can help you navigate ways to save on both products.
- Save with GoodRx. GoodRx can help you save over 90% off the average retail price of the generic versions of pregabalin and gabapentin. Generic pregabalin at certain pharmacies may be as low as $12.85 with a free GoodRx discount. However, many pharmacies don’t accept discounts on controlled substances. Generic gabapentin’s price at certain pharmacies may be as low as $10.71 with a free GoodRx discount.
- Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, brand-name Lyrica may be as little as $4 if you use the manufacturer’s savings card.
Can you take pregabalin and gabapentin together?
No. Combining pregabalin and gabapentin can exaggerate side effects, such as dizziness and drowsiness, and raise your risk for falls or accidents. It may also make it more likely to experience breathing problems.