Pregabalin is a valuable treatment for seizures and nerve pain. It’s also used off-label to treat some anxiety and sleep disorders. To use pregabalin safely, here are some interactions you should avoid.
- Pregabalin is an anticonvulsant and analgesic (painkilling) drug that is commonly prescribed for epilepsy and neuropathic (nerve) pain. It can be abused for the ‘high’ effect found at high doses
- Pregabalin doesn’t directly interact with most other drugs, but the effects can duplicate or stack with those of other CNS depressants to become dangerous
- Special care should be taken to avoid combining pregabalin with opioids
Understanding how pregabalin works
Pregabalin is an anticonvulsant that is also used to treat neuropathic (nerve-based) pain. Researchers are not entirely sure how pregabalin (and other gabapentinoids) work. Chemically, pregabalin is structurally similar to the neurotransmitter GABA, but it doesn’t appear to interact with GABA systems in the brain.[1]
Some of the effects of pregabalin come from its ability to bind to the alpha-2-delta parts of voltage-gated sodium channels.[2] Normally, sodium enters the cell through these channels, which triggers the release of neurotransmitters. When pregabalin is bound to those receptors, the gates don’t open properly, and the amount of neurotransmitter is decreased.[3]
This reduction in the amount of excitatory neurotransmitter released into the brain probably explains how pregabalin is able to reduce the sensation of pain, reduce convulsions, calm anxiety, and improve sleep.[2] It is possible, however, that there are other mechanisms of action that researchers haven’t discovered or understood yet.
The biggest culprits: What not to take with pregabalin
Because it is not processed significantly by the liver and doesn’t bind to plasma protein, pregabalin doesn’t have as many direct drug interactions as other medications.[4] That doesn’t mean you don’t need to be careful. There are still some substances that should be avoided when you’re taking pregabalin.
CNS depressants
The main group of substances that should not be taken with pregabalin are CNS depressants. [5][6] This includes anything that decreases activity in the central nervous system (CNS). Given that pregabalin reduces the amount of excitatory neurotransmitters in the brain, it can be risky to take any other substances that decrease activity in the central nervous system.
Common CNS depressants include alcohol, benzodiazepines, opioids, and muscle relaxants. These all operate in different ways, so they don’t interact directly with pregabalin, but the effects of the different drugs can combine and reduce activity too far. This can potentially lead to respiratory failure and can be fatal.
Not all substances that slow the CNS are obvious. Antihistamines, especially older versions, have a depressant effect on the CNS, even though this is not their primary function.[7] They should not be taken with pregabalin to avoid the risk of respiratory depression.[6] Similarly, certain herbal preparations and supplements designed to relax or calm you should not be taken at the same time as pregabalin due to their sedative effect.
Other medications and substances
Gabapentin is another gabapentinoid drug that operates in a very similar way to pregabalin. The two drugs are structurally similar and have the same mechanism of action, but they are not interchangeable. You should avoid taking gabapentin at the same time as pregabalin unless your doctor has specifically advised you to do so.
A rare but extremely serious side effect of pregabalin is angioedema. This is severe swelling of the face, which can restrict the airway and can be life-threatening. Another class of drugs, angiotensin-converting enzyme inhibitors (ACEs), also increases the risk of this side effect.[8] It’s important not to increase the risk of this complication by combining these drugs.
The renal system is key in removing pregabalin from the body, so it’s important to make sure that your doctor is aware of any medications you are taking that affect your kidney function.[4] If your kidney function decreases while taking pregabalin, it may cause your dose to become too high.
What to do if you've mixed pregabalin with other substances
This information is not intended to replace qualified medical care. If you have any concerns about substances you’ve taken at the same time as pregabalin, seek medical advice.
One of the biggest dangers of combining pregabalin with other substances is the slowing of CNS activity, which can reduce your heart rate, blood pressure, and breathing. In extreme cases, this can lead to coma and may be fatal. You might also become confused, which makes you less likely to notice that there’s a problem.
Having another responsible adult present can reduce these dangers because they can step in and call for emergency help if you develop any of these symptoms. If they become concerned, they should seek immediate medical help on your behalf.
Recognizing symptoms of dangerous interactions
The consequences of mixing pregabalin with other CNS depressant medications can be extremely serious, including heart block, seizures, and even death.[5] Knowing what to look out for can help you respond quickly in an emergency.
Signs of a dangerous drug interaction with pregabalin include: [6]
- Swelling of the face, neck, or tongue, especially if this starts to make breathing difficult
- Becoming confused, disoriented, or agitated
- Becoming very dizzy and lightheaded
- Feeling extremely sleepy or lethargic
- Breathing that is slowed, shallow, or difficult
- Becoming unresponsive, unable to answer questions or be woken up
- Having a bluish tint to the skin, especially if this is on their lips, fingers, or toes
If you or someone you are caring for develops any of these symptoms, this is a medical emergency, and you will need to seek medical help immediately.
How to avoid pregabalin interactions
Most people with chronic pain are taking many different medications to treat underlying health issues and alleviate their pain.[9] This makes it difficult, and even counterproductive, for people taking pregabalin for neuropathic pain to avoid all other drugs.[10]
Talk to your doctor about the medications you are currently taking and ask for a medication review if appropriate. During this review, be open about any over-the-counter medications or other substances you might be taking, especially anything designed to help you calm down or relax. This helps your doctor find the right medication to fit your needs.
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