From the Guidelines
Pregabalin is recommended as a first-line treatment for neuropathic pain, with a starting dose of 75mg twice daily, potentially increasing to a maximum of 300mg twice daily based on response and tolerability, as supported by the most recent and highest quality study 1.
Key Points
- Pregabalin works by binding to calcium channels in the nervous system, reducing the release of excitatory neurotransmitters and thereby decreasing pain signals and neuronal hyperexcitability.
- Common side effects include dizziness, drowsiness, dry mouth, edema, blurred vision, and weight gain.
- Patients should be aware that pregabalin can cause physical dependence, so it should never be stopped abruptly but rather tapered gradually under medical supervision.
- Pregabalin should be used with caution in patients with kidney impairment, and dose adjustments are often necessary in these cases.
Dosage and Administration
- The recommended starting dose is 75mg twice daily, with gradual increases as needed and tolerated.
- The maximum dose is 300mg twice daily, but higher doses may be associated with a greater rate of adverse effects.
- Pregabalin may provide analgesia more quickly than gabapentin, with the initial dosage of 150mg/d found to be efficacious in some trials.
Clinical Considerations
- Pregabalin is a Schedule V drug in the United States.
- It may impair thinking and reaction time, so caution is advised when driving or operating machinery.
- The efficacy and tolerability of pregabalin seem to be similar to those of gabapentin, but pregabalin has linear pharmacokinetics, and dosing is more straightforward.
Evidence-Based Recommendations
- The American Academy of Neurology recommends pregabalin as a first-line treatment for neuropathic pain, along with other medications such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants 1.
- A recent head-to-head trial suggested therapeutic equivalency for capsaicin, but pregabalin remains a preferred treatment option due to its established efficacy and safety profile 1.
From the FDA Drug Label
Pregabalin is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy Management of postherpetic neuralgia Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older Management of fibromyalgia Management of neuropathic pain associated with spinal cord injury
Pregabalin Uses: Pregabalin is used to treat various conditions, including:
- Neuropathic pain associated with diabetic peripheral neuropathy
- Postherpetic neuralgia
- Partial-onset seizures in patients 1 month of age and older
- Fibromyalgia
- Neuropathic pain associated with spinal cord injury 2
From the Research
Pregabalin Overview
- Pregabalin is a recently licensed and marketed antiepileptic drug for use as adjunctive treatment of partial epilepsy 3
- It acts at presynaptic calcium channels, modulating neurotransmitter release in the CNS, properties it shares with gabapentin 3
- Pregabalin has been used in the treatment of neuropathic pain, generalized anxiety disorder, and epilepsy 3, 4, 5
Efficacy of Pregabalin
- Three multi-centre randomised, double-blind, placebo-controlled trials have demonstrated an antiepileptic effect of pregabalin against placebo, as adjunctive therapy, with 31-51% of patients showing a 50% reduction in seizure frequency 3
- Pregabalin has been shown to be effective in the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia 4, 6
- Pregabalin may be beneficial as an adjunctive therapy in adult patients with generalized anxiety disorder (GAD) or social anxiety disorder (SAD) 4
Adverse Effects of Pregabalin
- Adverse effects of pregabalin are dose-related, with the commonest being somnolence, dizziness, and ataxia 3
- Weight gain was seen in 14% of patients on the highest dose of 600 mg/day 3
- The most commonly reported adverse effects are those affecting the central nervous system, including somnolence, dizziness, and headache 4
- Pregabalin is well-tolerated, with few serious adverse effects reported 5, 7
Pharmacokinetics and Pharmacodynamics
- Pregabalin has a linear pharmacokinetic profile, is completely absorbed, not bound to plasma proteins, not metabolized, and eliminated unchanged through the kidneys 5
- Doses must be adjusted in patients with renal insufficiency 5
- Pregabalin exerts its pharmacodynamic effect by modulating voltage-gated calcium channels 5