Can You Take Lyrica And Gabapentin Together?

In our latest question and answer, the pharmacist discusses whether or not you can safely take gabapentin and Lyrica (pregabalin) together.

Question

I am currently taking gabapentin 3600mg/day. It has been recommended that I also take pregabalin staring at 75mg and increasing over the next month to 150mg twice daily. Can these mediations be given together for neuropathic pain?

Asked by Riley On Jun 06, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Jun 06, 2022
Last updated Jun 06, 2022

Key points

  • Gabapentin and Lyrica (pregabalin) generally aren't used together due to their numerous similarities.
  • Taking both gabapentin and Lyrica together would generally be considered a 'therapeutic duplication', but there is some evidence of the potential positive benefits of this.
  • Nevertheless, preliminary studies show that their combined use may potentially provide synergistic pain-relieving effects and a decreased incidence of side effects. More data is needed, however.

Lyrica (pregabalin) and gabapentin generally aren't used together due to the similarity in how they work.

Nevertheless, preliminary studies evaluating the combined use of low doses of both drugs have found that there may be improved tolerability and pain-relieving effects when compared to the use of a single agent alone.

One such study, published in 'Current Medical Research and Opinion', states the following:

"Despite their similarities [Lyrica and gabapentin], they have been used in combination in both clinical and research situations, and have been noted to have a synergistic effect in pain control without concern for clinically significant pharmacokinetic interactions. This combined approach can be made use of to reduce the dose of an individual agent, its side effects, and to enhance therapeutic response compared to a single agent."

Unfortunately, most studies discussing the combined use of Lyrica and gabapentin are small and case-based, with no large clinical trials.

Larger scale studies need to be completed to know about the potential benefits and drawbacks of using both together.

In most situations (currently at least), a patient will only be prescribed one drug or either and the choice of a specific drug will depend on certain factors (e.g. cost, indication, contraindications, etc...).

This isn't to say both can't be used together in patients who have had an inadequate response to only one drug.

There doesn't appear to be any sort of interaction between the two (aside from similar side effects), and using both may at least be an alternative therapy worth trying for some.

Potential Advantages Of Both Together?

Two Capsules Next To Each Other

Some small-scale studies have shown that there likely is a synergistic analgesic effect when both are used together.

One such study says the following:

These comparisons [i.e. how Lyrica and gabapentin work] have a synergistic effect in the treatment of pain. Advantages of these compositions [Lyrica with gabapentin] include fewer side effects as lower dosages are needed. This increases patient compliance with the beneficial result of better control of pain.

The potential ability to use lower doses of both drugs, as the quote states, could be very beneficial when it comes to lowering the incidence of side effects without a loss in therapeutic efficacy.

Additionally, certain patient populations may stand to especially benefit, including those that cannot tolerate high doses of either drug.

One such population is the elderly, who generally have decreased kidney function compared to younger adults.

Using low doses of both drugs may offer the ability to use these drugs where they may have not even been an option before (due to the higher doses needed).

How Do They Work?

Both gabapentin and Lyrica (pregabalin) are structurally similar. In fact, both are structural analogs of GABA (gamma-aminobutyric acid), a naturally occurring inhibitory neurotransmitter.

They both work more or less the same way, having anxiolytic (anti-anxiety), analgesic (pain-relieving), and antiepileptic (anti-seizure) properties. They both (likely):

  • Increases neuronal GABA levels.
  • Increase in glutamic acid decarboxylase activity (which increases the conversion of glutamate to GABA.
  • Reduce neuronal calcium currents.

Both Lyrica and gabapentin are distinct from most other pain and anxiety medications based on their mechanism alone.

They are not thought to affect other common neurotransmitters, like serotonin, dopamine, and norepinephrine like antidepressants do. They also don't bind to opioid or benzodiazepine receptors either.

Potency Comparison

Although Lyrica and gabapentin are quite similar, one major point of differentiation is their potency and Lyrica is far more potent on a milligram to milligram basis than gabapentin.

Studies vary in terms of just how much more potent Lyrica is, but it generally is reported to be between three to ten times more potent. This is clearly evidenced by the available strengths of both medications.

Lyrica (immediate-release capsules) is available in the following strengths:

  • 25mg
  • 50mg
  • 75mg
  • 100mg
  • 150mg
  • 200mg
  • 225mg
  • 300mg

For gabapentin (immediate-release):

  • 100mg
  • 300mg
  • 400mg
  • 600mg
  • 800mg

Another point of differentiation between Lyrica and gabapentin is their duration of action, with Lyrica lasting slightly longer in most individuals.

While Lyrica is most often dosed twice a day, gabapentin is generally dosed more often, up to three to four times daily. Both are available in extended-release formulations too.

Studies also show that Lyrica may be better tolerated than gabapentin.

Most side effects of the drugs are 'dose-dependent', meaning they occur more often with increasing dosages.

Due to the lower doses used for Lyrica, side effects tend to occur with less frequency.

Controlled-Substance Status

It is important to point out that Lyrica is a Schedule V controlled substance, while gabapentin is not federally classified as a controlled substance, but is a controlled substance in certain states.

This is because Lyrica has a higher risk of misuse and abuse compared to gabapentin for the following reasons:

  • It is more potent
  • It is absorbed more quickly
  • It has greater bioavailability
  • It is more likely to cause dependence

Final Words

From my experience, working previously in a retail pharmacy, it would be very uncommon to see someone on both Lyrica and gabapentin due to their similarity.

In fact, most pharmacy computer systems would flag a patient on both as a 'therapeutic duplication', which would then likely need to be reviewed more closely by the pharmacist and/or the insurance company.

Having said this, as described in this answer, there have been preliminary studies discussing the potential benefits of combined therapy, which to review, include:

  • Synergetic pain-relieving effects
  • Lower dosages
  • Decreased incidence of side effects.

If you haven't had positive effects from one drug, your doctor may decide to try both.

They don't seem to interact with each other or put you at risk for any additional harm. Just know that more studies are needed to determine the place in therapy (if any) of combined therapy.

References

  • Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true?, PubMed
  • Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for Concern?, PubMed
  • Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain, PubMed
  • A synergistic combination: gabapentin and pregabalin, Google
  • ClinicalKey Lyrica Monograph, ClinicalKey (Subscription Required)
  • ClinicalKey Gabapentin Monograph, ClinicalKey (Subscription Required)

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 11 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication related questions!

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