Pregabalin

What Does Pregabalin Do?

Pregabalin is used primarily for the treatment of nerve pain and as a supporting therapy for adults with epilepsy experiencing partial seizures. Off-label usage encompasses the treatment for general anxiety disorder and restless leg syndrome.

How Does Pregabalin Work? (the complicated stuff)

Pregabalin effectively reduces the perception of pain - this is achieved through its binding to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. The binding reduces calcium inflow into neurons, thereby lowering the release of excitatory neurotransmitters such as glutamate, noradrenaline, and substance P. As a result, pain signalling is modulated, leading to symptom alleviation.

Drug Type and Category of Pregabalin

Pregabalin is classified as an anticonvulsant and is also categorised as a gabapentinoid, which means it is a derivative of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.

What dosage of Pregabalin should you be taking?

NICE Guidelines ¹

Initial Dose

150 mg per day, given in two to three divided doses

Dose Adjustment

If necessary, the dose can be increased after 3-7 days to 300 mg per day, given in two to three divided doses

The maximum recommended dose is 600 mg per day, given in two to three divided doses

Administration

Pregabalin can be taken with or without food

When discontinuing pregabalin, it should be tapered gradually over at least one week

Dosage Adjustments for Renal Impairment

Dose adjustments are necessary for patients with reduced renal function. 

• For patients with creatinine clearance (CrCl) ?60 mL/min, no dose adjustment is required
• For CrCl 30-60 mL/min, the dose should be reduced by 50%
• For CrCl 15-30 mL/min, the dose should be reduced by 75%
• For CrCl <15>
  

What are the side-effects of Pregabalin?

Most Common Side Effects

• Dizziness
• Sleepiness or drowsiness
• Blurred vision
• Dry mouth
• Weight gain
• Swelling of hands, legs or feet
• Headache (extended-release tablets)
• Tiredness (extended-release tablets)
• Nausea (extended-release tablets)
• Difficulty concentrating (capsules or solution)
• Increased appetite (in children)

Serious Side Effects

• Severe allergic reactions including trouble breathing, swelling of face/lips/tongue, rash, hives
• Suicidal thoughts or actions
• Respiratory depression (slow, shallow breathing), especially when used with opioid pain medicines
• Unexplained muscle pain, weakness or tenderness
• Angioedema (swelling of lips, face, tongue or throat)
• Fluid retention and weight gain, especially in those with heart problems
• Blurred vision, double vision, clumsiness, unsteadiness, trouble with thinking
• Sores or skin problems, especially in those with diabetes
  

Drug Interactions

1. Central Nervous System (CNS) Depressants: Pregabalin can enhance the sedative effects of other CNS depressants, including alcohol, benzodiazepines (e.g., diazepam, lorazepam), and other sedative medications. This can lead to increased drowsiness, dizziness, and risk of overdose.
2. Opioids: Combining pregabalin with opioids (e.g., oxycodone, morphine) can increase the risk of respiratory depression, sedation, and potentially overdose.
3. Antidiabetic Medications: Pregabalin may affect blood sugar levels, potentially altering the effectiveness of antidiabetic medications. Close monitoring of blood glucose levels is advisable.
4. Antacids: Antacids containing aluminum or magnesium may interfere with the absorption of pregabalin if taken simultaneously. It’s recommended to space out the administration of these medications.
5. Diuretics: There is some evidence that pregabalin can affect fluid balance, which may alter the effectiveness of diuretics (e.g., furosemide).
6. Other Antiepileptic Drugs: While pregabalin is used to treat epilepsy, combining it with other antiepileptic drugs (e.g., carbamazepine, phenytoin) can require dose adjustments due to potential changes in seizure control and side effects.
7. CYP Enzyme Modifiers: Pregabalin is not significantly metabolised by cytochrome P450 enzymes, so interactions with CYP enzyme inhibitors or inducers are generally minimal.
8. Herbal Supplements such as St. John’s Wort, which can affect serotonin levels, might interact with pregabalin, especially if taken with other serotonergic drugs.
9. Blood Thinners: While not a major interaction, it’s important to monitor for any signs of bleeding or bruising when pregabalin is used with anticoagulants or antiplatelet medications.
10. Renal Impairment: Pregabalin is excreted via the kidneys, so impaired renal function can lead to higher drug levels and increased risk of side effects. Dose adjustments may be necessary based on renal function.

Natural Alternatives to Pregabalin

Physiotherapy, osteopathy and other manual therapies can help significantly with nerve, joint and muscle pain without the need for pregabolin. A skilled therapist will be able to work with the patient over a number of sessions to help reduce pressure on the nerve, and reduce persistent pain. Working holistically can help too, with advice on exercises, weight loss and healthy living. 

The problem with pregabalin is simple: how do you come off it? Hence, many people are resorting to long-term use. This is where working with a therapist is necessary. 

 Here are some other natural alternatives that may help relieve neuropathic pain:

• Butea monosperma: Pretreatment with this herb significantly reduced hyperalgesia and allodynia in a rat model of vincristine-induced neuropathic pain, likely due to its neuroprotective, antioxidant and calcium channel inactivating effects. ²
• Citrullus colocynthis: This herb has shown promise in animal models of neuropathic pain. ²
• Rosmarinus officinalis (Rosemary): Rosemary and its active compound rosmarinic acid demonstrated anti-inflammatory, antioxidant and neuroprotective effects in rat models of neuropathic pain. ²
• Rubia cordifolia: This herb reduces pain behaviors and oxidative stress in animal models of neuropathic pain. ²
• Salvia officinalis (Sage): Sage extracts exhibited antinociceptive (pain-relieving) effects in mice. ²
• Vitamin B12: Deficiency is linked to neuropathic pain. Supplementation may help. ³
• Alpha-lipoic acid: This antioxidant supplement has been shown to reduce neuropathic pain. ³
• Palmitoylethanolamide (PEA): An endogenous fatty acid amide with anti-inflammatory and pain-relieving effects. ⁴
• Medical cannabis: The cannabinoids THC and CBD interact with the endocannabinoid system to reduce pain and inflammation. Cannabis may be a safe and effective short-term treatment for neuropathic pain. ³
• Relaxation techniques: Breath control and other stress-reducing practices can help quell the stress response that exacerbates neuropathic pain. ³

Interesting facts about Pregabalin

In some countries, pregabalin is classified as a controlled substance due to its potential for misuse and dependence. This classification can affect how the medication is prescribed and dispensed.

Pregabalin is chemically related to gabapentin (another medication used for similar conditions) but has a higher binding affinity. This can result in more predictable and effective therapeutic effects.

Disclaimer

This article is generated for informational purposes only. It was created in December 2024. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://bnf.nice.org.uk/drugs/pregabalin/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960749/
3. https://lyphe.com/natural-remedies-for-nerve-pain/
4. https://onlinelibrary.wiley.com/doi/full/10.1155/2016/7917528