Zhou Q, Zheng J, Yu L, Jia X. Pregabalin monotherapy for
epilepsy. Cochrane
Database Syst Rev. 2012 Oct 17;10:CD009429.
Abstract
BACKGROUND:
Many people with epilepsy suffer from poorly controlled
seizures, despite current antiepileptic treatments. Due to high rates of
treatment resistance, there is interest in new pharmacological treatment
options such as pregabalin. However, it remains unclear whether existing
evidence of pregabalin is rigorous enough to support its monotherapy.
OBJECTIVES:
To determine the efficacy and tolerability of pregabalin in
people with epilepsy.
SEARCH METHODS:
We searched the Cochrane Epilepsy Group's Specialized
Register (August 2012), the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library 2012, Issue 7 ), MEDLINE (1946 to August week
1, 2012), EMBASE (1974 to August 2012) and the Chinese Biomedical Literature
Database (CBM) (1978 to August 2012). No language restrictions were imposed.
SELECTION CRITERIA:
Randomised controlled trials (RCTs) comparing pregabalin
with placebo or another antiepileptic drug monotherapy for epilepsy.
DATA COLLECTION AND ANALYSIS:
Two review authors (QZ and LY) independently extracted trial
data and assessed trial quality. We assessed the following outcomes: (1) time
to withdrawal after randomisation; (2) time to achieve six-, 12- or 24-month
remission; (3) the proportion of participants who remained seizure-free for six
or more continuous months; (4) time to first seizure after randomisation; (5)
validated quality of life measures; (6) health economic outcomes; (7) adverse
effects. We expressed time-to-event outcomes as hazard ratios (HRs) with 95%
confidence interval (CI), where an HR > 1 indicates an event is more likely
to occur earlier on pregabalin than the comparator.
MAIN RESULTS:
Two short-term studies involving 753 participants met the
inclusion criteria. Only one study investigated the effects of pregabalin
compared with lamotrigine in patients with newly diagnosed partial seizures,
and the other study investigated the effects of pregabalin compared with
gabapentin in hospitalised patients with refractory partial epilepsy. There
were no studies on generalised-onset tonic-clonic seizures (with or without
other generalised seizure types).We found that pregabalin was inferior in comparison
to lamotrigine when measuring time to withdrawal due to inadequate seizure
control after dose stabilisation from randomisation: hazard ratio (HR) 4.52;
95% confidence interval (CI) 1.93 to 10.60; time to achieve six-month remission
after dose stabilisation from randomisation: HR 0.56; 95% CI 0.41 to 0.76; the
proportion of participants who remained seizure-free for six or more continuous
months: RR 0.76, 95% CI 0.67 to 0.87 (Europe: 0.83, 95% CI 0.69 to 0.99; Asia:
RR 0.70, 95% CI 0.57 to 0.86; the Americas: RR 0.62, 95% CI 0.33 to 1.19); and
time to first seizure after dose stabilisation from randomisation: HR 1.74; 95%
CI 1.26 to 2.39. There was no significant difference in safety-related outcomes
between pregabalin and lamotrigine, but more participants in the pregabalin
group developed somnolence, weight increase and convulsion. Pregabalin was
better than gabapentin when measuring time to withdrawal due to all reasons
after randomisation: HR 0.25; 95% CI 0.11 to 0.57; and time to withdrawal due to
inadequate seizure control after randomisation: HR 0.41; 95% CI 0.18 to 0.92.
No significant difference was found in safety-related outcomes between
pregabalin and gabapentin. But we found some limitations in the study design
which may have had an influence on the results.
AUTHORS' CONCLUSIONS:
Pregabalin seems to have similar tolerability but inferior
efficacy in comparison to lamotrigine for newly diagnosed partial seizures.
However, considering the limitations in the study design (such as the
short-term follow-up and the low initial target dose selection), the results
should be interpreted with caution. The available data were too limited to draw
any conclusions between pregabalin and gabapentin. The result indicated that
the treatment effects were influenced by the study regions. The clinical
disadvantage of pregabalin was more prominent in Asia when compared with
lamotrigine. We should determine whether pregabalin has ethnic differences in
the treatment of epilepsy in the future. This review does not inform any
treatment policy for patients with generalized onset tonic-clonic seizures.
Further long-term trials are needed to investigate the genuine effectiveness of
pregabalin as monotherapy.
Pruskowski J, Arnold RM. A comparison of pregabalin and gabapentin in palliative care #289. J Palliat Med. 2015 Apr;18(4):386-7.
ReplyDeleteThe major pharmacokinetic difference between gabapentin and pregabalin is their absorption from the GI tract. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900–3600 mg/day, while pregabalin remains ≥90% irrespective of dosage. This suggests that dose escalations of gabapentin are accompanied by a therapeutic ceiling effect, although this has not been proven in studies. Neither medication binds to plasma proteins, both undergo negligible metabolism, and both are renally excreted with terminal half-lives of five to six hours. Overall, literature suggests that pregabalin has a small pharmacokinetic advantage over gabapentin, although there is little evidence-based literature to support its clinical superiority in patient care…
The onset of pregabalin is approximately 25 minutes, compared to one to three hours for gabapentin. Equally important, pregabalin can be more rapidly titrated to an effective dose range than gabapentin (one to two days for pregabalin versus approximately nine days for gabapentin)…
Research suggests a target dose of at least 900–1800 mg/day (in divided doses) of gabapentin to maintain analgesia for persistent pain, although doses as high as 6000 mg/day have been taken for cancer pain. With pregabalin, it appears analgesia can be achieved and maintained at any dose…
Gabapentin is FDA approved for postherpetic neuralgia and adjunctive therapy in the treatment of partial onset of seizures, while pregabalin is approved for diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and neuropathic pain associated with spinal cord injury, as well as an adjunctive therapy for adult patients with partial onset seizures. Research suggests the number needed to treat (NNT)—the number of patients needed to be treated in order for one patient to benefit—in diabetic neuropathy for pregabalin is four (for a 50% reduction at 600 mg/day); while gabapentin had only a small effect on pain reduction (therefore the NNT was not reported). Although gabapentin is frequently given to patients with chemotherapy-induced peripheral neuropathy, few controlled trials have been conducted and investigations have shown conflicting results. There has been only one study comparing the efficacy of gabapentin and pregabalin in neuropathic cancer pain. In this double-blind, randomized, placebo-controlled trial, patients were given amitriptyline, gabapentin, pregabalin, or placebo. There were statistically lower VAS scores in the pregabalin group when compared to the others. The authors also noted a statistically and clinically significant morphine-sparing effect of pregabalin. This single, midquality trial has not been replicated…
Research suggests the number needed to treat (NNT)—the number of patients needed to be treated in order for one patient to benefit—in diabetic neuropathy for pregabalin is four (for a 50% reduction at 600 mg/day); while gabapentin had only a small effect on pain reduction (therefore the NNT was not reported). Although gabapentin is frequently given to patients with chemotherapy-induced peripheral neuropathy, few controlled trials have been conducted and investigations have shown conflicting results. There has been only one study comparing the efficacy of gabapentin and pregabalin in neuropathic cancer pain. In this double-blind, randomized, placebo-controlled trial, patients were given amitriptyline, gabapentin, pregabalin, or placebo. There were statistically lower VAS scores in the pregabalin group when compared to the others. The authors also noted a statistically and clinically significant morphine-sparing effect of pregabalin.8 This single, midquality trial has not been replicated…
Pregabalin has some pharmacokinetic advantages over gabapentin, but is much more costly. There are no clear data demonstrating improved clinical outcomes of one agent over the other.
Snedecor SJ, Sudharshan L, Cappelleri JC, Sadosky A, Desai P, Jalundhwala YJ, Botteman M. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury. J Pain Res. 2013 Jul 11;6:539-47.
ReplyDeleteAbstract
BACKGROUND:
Management of neuropathic pain (NeP) associated with spinal cord injury (SCI) is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP.
METHODS:
Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS) or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs) were also assessed, for which Bayesian meta-analytic indirect comparisons were performed.
RESULTS:
Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136). Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was -1.72 for pregabalin, -1.65 for amitriptyline, -1.0 for duloxetine, -1 (median) for levetiracetam, -0.27 for gabapentin, 1 (median) for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with placebo, and no differences between placebo and any treatment for discontinuations.
CONCLUSIONS:
Studies of SCI-associated NeP were few, small, and reported insufficient data for quantitative comparisons of efficacy. However, available data suggested pregabalin was associated with more favorable efficacy for all outcome measures examined, and that the risks of AEs and discontinuations were found to be similar among the therapies.