Can We Lump All Gabapentinoids Together?
General practitioners often encounter peripheral neuropathic pain in their practice. One of the primary modalities for treating both painful diabetic neuropathy and postherpetic neuralgia is gabapentinoids, specifically gabapentin and pregabalin. Are these substances completely interchangeable, or do their efficacy and practical application differ?
Introduction
Neuropathic pain is a common yet therapeutically challenging complaint for many patients and has a significant negative impact primarily on quality of life. The approach to therapy must be comprehensive and utilize all available modalities according to the individual needs of the patient. In addition to pharmacotherapy, psychotherapy, physical therapy, and invasive techniques are certainly also considered. One of the fundamental pharmacological options for influencing neuropathic pain are gabapentinoids.
Gabapentinoids
The term “gabapentinoids” refers to derivatives from gamma-aminobutyric acid (GABA) substituted at position 3. Currently, in the Czech Republic, these include gabapentin and pregabalin. Both of these drugs can be used in the treatment of peripheral neuropathic pain.
Pregabalin is the pharmacologically active S-enantiomer of 3-isobutyl-GABA. It binds with high affinity to the α2δ subunit of voltage-gated calcium channels, which prevents the influx of calcium into the interior of the neuronal process. This process leads to a limitation of the fusion of secretory vesicles with the presynaptic membrane and thus also the subsequent release of mediators into the synaptic cleft (especially glutamate, substance P, norepinephrine, and CGRP peptide). The consequence of suppressed transmitter release into the synaptic cleft is a fundamental reduction in neuronal hyperexcitability and the limitation of abnormally emerging synchronization of action potentials of individual neurons.
Compared to gabapentin, pregabalin's binding to the mentioned calcium channel subunit is several times (3–10×) higher. Pregabalin also has higher oral bioavailability and, under regular conditions, its absorption is not saturable (whereas gabapentin’s absorption decreases due to the limited activity of the L-amino acid transporter).
Dosage and Method of Use
Treatment with gabapentin begins with the following titration: 300 mg on the 1st day once daily, 2nd day twice daily, 3rd day three times daily. Alternatively, an initial dose of 900 mg/day can be administered in 3 equally divided doses. The dose can then be increased by 300 mg/day every 2–3 days up to a maximum of 3600 mg/day, depending on the individual response and tolerability of each patient. Some patients may benefit from a slower titration. The shortest time to reach a dose of 1800 mg/day is 1 week, 2400 mg/day in 2 weeks, and 3600 mg/day in 3 weeks.
Pregabalin is used exclusively orally. Therapy can be initiated with a dose of 150 mg daily divided into 2 or 3 doses. Depending on the individual response and tolerability of the patient, the dose can be increased to 300 mg daily after an interval of 3–7 days and, if necessary, after another 7 days up to a maximum dose of 600 mg daily. Treatment with pregabalin requires a significantly shorter titration period at the start compared to gabapentin.
Pregabalin May Help Where Gabapentin Fails
An analysis by American and Danish authors using data from 18 randomized double-blind, placebo-controlled studies with a total of 4724 participants investigated the therapeutic effect of pregabalin on neuropathic pain in patients previously untreated and in patients previously unsuccessfully treated with gabapentin.
No significant difference in therapeutic effect (pain, pain-related sleep disturbances) was observed between these two cohorts regardless of dosing. The analysis clearly demonstrated the benefit of pregabalin in individuals previously treated with gabapentin without a corresponding therapeutic response. The differing efficacy of the two gabapentinoids is thus evident.
This analysis only underscores the importance of an individualized approach to the treatment of neuropathic pain, including the possibility of switching drugs within the group with a similar mechanism of action. The insufficient effect or intolerance of gabapentin does not exclude the success of pregabalin therapy.
(dos)
Source: Markman J. D., Jensen T. S., Semel D. et al. Effects of pregabalin in patients with neuropathic pain previously treated with gabapentin: a pooled analysis of parallel-group, randomized, placebo-controlled clinical trials. Pain Pract 2017; 17 (6): 718–728, doi: 10.1111/papr.12516.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
