Pregabalin

Pregabalin a gamma-aminobutyric acid analogue, an antiepileptic (available in capsule form or as a solution), which reduces neuronal excitability in the central nervous system It therefore has analgesic, anti-epileptic, anxiolytic and sedative effects.

Pregabalin is quickly absorbed on an empty stomach. The maximum plasma concentration is reached within one hour. After 24 to 48 h, a steady state is reached after repeated intake. After about 6.5 hours the half-life is reached in kidney healthy patients.

Pregabalin binds to a subunit of voltage-gated calcium channels and does not act in the GABA-ergic system as initially thought. Animal studies suggest that it acts on neuronal Ca2+ channels. It binds selectively and with high affinity to the α2-δ-subunit of voltage-gated Ca2+ channels, mainly at the terminals of primary afferent nociceptors in the spinal cord, thereby modulating calcium ion influx into the nerve cell terminal. In pathological sensitization of the primary afferent nociceptors, as is typical in neuropathic pain syndromes, the reduced calcium ion influx leads to a reduced release of excitatory transmitters (e.g., the excitatory amino acid glutamic acid and substance P) and thus to an attenuation of overexcitation.

Pregabalin is used in adults for epilepsy without secondary generalization, peripheral and central neuropathic pain, and generalized anxiety disorder. Furthermore, the substance is indicated for postzosteric pain (Arnold LM et al. 2017).

Capsules or solution with pregabalin can be taken 2-3x/day regardless of meals. Depending on the indication, the recommended dose ranges from 150 to 600 mg.

Neuropathic pain: initiation of therapy: 150 mg daily, divided into two or three single doses. Depending on individual response and individual tolerance, the dose may be doubled after a few days. After two weeks, it can be increased to 600 mg daily - this is the maximum recommended dose.

Epilepsy: start of therapy: 150 mg daily, divided into two or three single doses. Depending on individual response and individual tolerability, the dose may be doubled after one week. After another week, it may be increased to 600 mg daily - this is the maximum recommended dose.

Generalized anxiety disorder: initiation of therapy: 150 mg daily, divided into two or three single doses. Depending on individual response and individual tolerance, the dose may be doubled after one week. After another week, it may be increased to 450 mg daily. The maximum recommended daily dose of 600 mg should not be increased until another week has elapsed.

Discontinuation of pregabalin: It is important not to stop medication with pregabalin abruptly but to taper it off over a week.

Among the most common side effects under Pregabalin therapy are:

Very common: drowsiness, drowsiness, headache.

Common: nasopharyngitis, appetite increase; euphoria; confusion; irritability; insomnia; loss of libido; ataxia; coordination disorders; memory disorders; attention disorders; sedation; erectile dysfunction; (peripheral) edema; gait disorders; falls

Less common: neutropenia; hypersensitivity; mood swings; cognitive disorders; sinus bradycardia; heart failure; facial flushing; urticaria; hyperhidrosis; pruritus; joint swelling

Rare: Angioedema

Lyrica®

Based on currently available study data, the following characteristics of pregabalin can be summarized in comparison to other drug therapy options:

• Known mechanism of action
• Good study record (2 750 patients, 10 randomized controlled trials, proof of efficacy)
• Broad effect on comorbidities (anxiety, sleep, mood)
• Rapid onset of action within first week
• No slow titration necessary
• Long-lasting effect (> 650 patients > 60 weeks in open-label studies)
• No interactions
• Few side effects

Zoster neuralgia:

A meta-analysis compared pregabalin and gabapentin (14 randomized controlled trials with 3,545 patients: 926 on pregabalin, 1,256 on gabapentin, and 1,363 on placebo). Both agents improved pain scores on the 11-item numeric rating scale. However, pregabalin reduced pain by a mean of 1.65 points more than gabapentin. Pregabalin also performed better on sleep disturbances. However, pregabalin significantly increased the risk of adverse effects such as weight gain, fatigue, and dizziness compared with placebo, whereas this was not evident with gabapentin (Cao X et al. 2022).

1. Arnold LM et al (2017) Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. Postgrad Med 129: 921-933.

2. Cao X et al (2022): A Meta-analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Pregabalin and Gabapentin in the Treatment of Postherpetic Neuralgia. Pain Therapy DOI: 10.1007/s40122-022-00451-4.