Dataset Information

Patterns of gabapentin and pregabalin use and misuse: Results of a population-based cohort study in France.

ABSTRACT:

Aims

The aim of this study was to assess the use and factors associated with the misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population.

Methods

New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses than recommended. Cox proportional hazard regression models were performed to identify associated factors of misuse.

Results

Misuse was more frequent in the 8692 new users of pregabalin (12.8%) than in the 1963 gabapentin (6.6%) or the 3214 duloxetine new users (9.7%) (P < 0.001). Factors associated with misuse were pregabalin (hazard ratio [HR] 1.48; 95% confidence interval [CI] [1.29-1.69]), age (HR_{[18-45] versus > 70 years} 1.98 [1.70-2.31] and HR_{[58-70] versus > 70 years} 1.25 [1.06-1.47]), multiple prescribers (HR_{2 or 3 versus 1 prescriber} 1.29 [1.15-1.45]; HR_{4 or more versus 1 prescriber} 1.54 [1.30-1.83]), cancer (1.28 [1.11-1.47]), multiple sclerosis (1.53 [1.07-2.18]), neuropathy (1.85 [1.19-2.89]), depression (1.26 [1.07-1.49]) and methadone (2.61 [1.16-5.84]). After this first episode of drug misuse, 11.6% of gabapentin and 10.7% of pregabalin misusers developed a primary addiction.

Conclusion

In a cohort of new users, misuse is more likely to occur in new users of pregabalin, with different associated factors of misuse compared to gabapentin and duloxetine. Health professionals and prescribers must be aware of this misuse potential, which could lead to abuse and dependence.

SUBMITTER: Driot D

PROVIDER: S-EPMC6533441 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Patterns of gabapentin and pregabalin use and misuse: Results of a population-based cohort study in France.

Driot Damien D Jouanjus Emilie E Oustric Stéphane S Dupouy Julie J Lapeyre-Mestre Maryse M

British journal of clinical pharmacology 20190328 6

<h4>Aims</h4>The aim of this study was to assess the use and factors associated with the misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population.<h4>Methods</h4>New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses ...[more]

PMID: 30737829

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Project description:IntroductionWhile use of augmentation of labor (AL) is appropriate for labor dystocia, it is frequently used inadequately and unnecessarily. The objective was to assess at a national level, the frequency and determinants of misuse of augmentation of labor (AL).Material and methodsWomen of the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. "Misuse of AL" was defined by artificial rupture of the membranes (ROM) and/or oxytocin within one hour of admission and/or duration between ROM and oxytocin of less than one hour. Women, labor and maternity unit's characteristics were compared between the "misuse of AL" and "no misuse of AL" groups by bivariate analysis. To identify the determinants of misuse of AL, a multivariable multilevel logistic regression was performed taking into account the data's hierarchical structure (first level: women, second level: maternity units).ResultsAmong the 7196 women included, 1524 (21.2%) had a misuse of AL. The determinants of misuse of AL were middle school educational level (reference high school), aOR = 1.21; 95%CI[1.01-1.45], gestational age at delivery ≥41weeks (reference 39-40 weeks), aOR = 1.19; 95%CI[1.00-1.42], cervical dilation ≥6cm at admission (reference <3cm), aOR = 1.39; 95%CI[1.10-1.76], epidural analgesia aOR = 1.63; 95%CI[1.35-1.96], delivery in a private hospital (reference public teaching hospital), aOR = 2.25; 95%CI[1.57-3.23]; and maternity units with <1000 deliveries/year and 1000-1999 deliveries/year (reference ≥3000 deliveries/year), respectively aOR = 1.52; 95%CI[1.11-2.08] and aOR = 1.42; 95%CI[1.05-1.92]. Less than 3% of the variance was explained by women characteristics, and 24.17% by the maternity units' characteristics.ConclusionsIn France, one spontaneous laboring woman among five is subject to misuse of AL. The misuse is mostly explained by maternity unit's characteristics. The determinants identified in this study can be used to implement targeted actions in small and private maternity units.

Project description:BackgroundPregabalin and gabapentin improve neuropathic pain symptoms but there are emerging concerns regarding their misuse. This is more pronounced among patients with substance use disorder, particularly involving opioids. Co-ingestion of gabapentinoids with opioids is increasingly identified in opioid related deaths, however, the molecular mechanism behind this is still unclear. We have sought to determine whether pregabalin or gabapentin directly modulates acute μ receptor signaling, or μ receptor activation by morphine.MethodsThe effects of pregabalin and gabapentin were assessed in HEK 293 cells stably transfected with the human μ receptor. Their effect on morphine induced hyperpolarization, cAMP production and ERK phosphorylation were studied using fluorescent-based membrane potential assay, bioluminescence based CAMYEL assay and ELISA assay, respectively. Pregabalin/gabapentin effects on morphine-induced hyperpolarization were also investigated in AtT20 cells.ResultsPregabalin or gabapentin (1 µM, 100 µM each) did not activate the µ receptor or affect K channel activation or ERK phosphorylation produced by morphine. Neither drug affected the desensitization of K channel activation produced by prolonged (30 min) application of morphine. Gabapentin (1 µM, 100 µM) and pregabalin (1 µM) did not affect inhibition of forskolin-stimulated cAMP production by morphine. However, pregabalin (100 µM) potentiated forskolin mediated cAMP production, although morphine still inhibited cAMP levels with a similar potency to control.DiscussionPregabalin or gabapentin did not activate or modulate µ receptor signaling in three different assays. Our data do not support the hypothesis that gabapentin or pregabalin augment opioid effects through direct or allosteric modulation of the µ receptor. Pregabalin at a high concentration increases cAMP production independent of morphine. The mechanism of enhanced opioid-related harms from co-ingestion of pregabalin or gabapentin with opioids needs further investigation.

Project description:BackgroundGabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events.MethodsThis retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts.ResultsBoth gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease.ConclusionIn patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Project description:Background and objectivesThere are limited data examining the real-world use of gabapentin and pregabalin for the treatment of post-herpetic neuralgia (PHN). This study examines dosing patterns, therapy outcomes, healthcare utilization and costs of patients with PHN who initiate treatment with gabapentin or pregabalin.MethodsThis was a retrospective administrative claims data analysis from July 2005 to February 2010. Patients with PHN initiating gabapentin or pregabalin (index therapy) from January 2006 to February 2009 were identified and were observed for 12 months after index therapy initiation. Outcomes were mean daily dosages of the index therapy, attainment of minimally effective dosages of gabapentin (≥ 1,800 mg/day) or pregabalin (≥ 150 and ≥ 300 mg/day) persistence, discontinuation, index therapy switching, addition of neuropathic pain medications to index therapy, and healthcare resource use and costs.Results1,645 patients were identified. The mean daily dosage was 826 mg for gabapentin and 187 mg for pregabalin. Only 52.6 % of patients initiating gabapentin and 56.9 % initiating pregabalin obtained a refill during the post-index period. Approximately 14 % of patients treated with gabapentin reached the target dosage (1,800 mg/day). For pregabalin, 87 % reached ≥ 150 mg/day and 27 % reached ≥ 300 mg/day. On average, patients took 10 weeks to reach 1,800 mg/day gabapentin, and 5.0 and 9.2 weeks to reach ≥ 150 mg/day and ≥ 300 mg/day pregabalin, respectively. Approximately one-third of patients in both index therapy cohorts added a pain medication; more than half added opioids. The percentage of patients switching from either drug (57 %) or adding a therapy (34 %) were similar between index therapy cohorts; opioids were the most common therapy patients switched to or added.ConclusionIt appears that gabapentin and pregabalin are not used effectively to treat PHN. Suboptimal dosing and discontinuation may be associated with supplementary use of other analgesics, especially opioids.

Dataset Information

Patterns of gabapentin and pregabalin use and misuse: Results of a population-based cohort study in France.

Aims

Methods

Results

Conclusion

Publications

Patterns of gabapentin and pregabalin use and misuse: Results of a population-based cohort study in France.

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