1. Home
  2. gabapentin

gabapentin

Gabapentin Increasingly Implicated in Overdose Deaths

Author/s: 
Kuehn, B. M.

Gabapentin Increasingly Implicated
in Overdose Deaths
Postmortem toxicology tests detected gabapentin in almost 1 in 10 US overdose deaths
between 2019 and 2020.In about half of the
cases, a medical examiner or coroner ruled
the drug was a cause of the death, according to a report from the CDC’s Division of
Overdose Prevention.
The US Food and Drug Administration
(FDA) approved gabapentin for treating seizures and pain associated with shingles. But
growing off-label prescribing of gabapentin for nerve pain and other conditions contributed to its prescription rate doubling
from about 13 to 27 per 1000 insurance beneficiaries between 2009 and 2016. In fact,
by 2019, gabapentin had become the
seventh most prescribed drug in the US.
Gabapentin is sometimes used to amplify the effects of illicit opioids. In late 2019,
the FDA warned that gabapentin might
cause serious breathing difficulties when
usedwith drugs that depress the central nervous system, such as opioids, antianxiety
medications, and antidepressants.
Now, data from the State Unintentional
Drug Overdose Reporting System from 23
states and the District of Columbia suggest
that gabapentin’s role inUS overdose deaths
may be growing.Overall, toxicology tests detected gabapentin in 5687 overdose deaths
between 2019 and 2020—about 10% of all
cases with test results available. Overdose
deaths in which gabapentin was detected
doubled from 449 in the first quarter of 2019
to 959 in the second quarter of 2020.
The proportion of these cases thatmedical examiners ruled were caused by the drug
increased from 50% in early 2019 to 55% by
late 2020. About 90% of these cases also involved opioids, primarily illicitly manufactured fentanyl. About 83% of deaths caused
by gabapentin occurred amongWhite adults
aged 35 to 54 years.
“Personswho use illicit opioidswith gabapentinshouldbeeducatedabouttheincreased
risk for respiratorydepressionanddeath,” the
authors wrote. − Bridget M. Kuehn, MSJ

Keywords 
gabapentin Insurance Benefits Off-Label Use Drug Overdose

Non-Surgical Interventions for Lumbar Spinal Stenosis Leading To Neurogenic Claudication: A Clinical Practice Guideline

Author/s: 
Bussieres, A., Cancelliere, C., Ammendolia, C., Comer, C. M., Zoubi, F. A., Chatillon, C. E., Chernish, G., Cox, J. M., Gliedt, J. A., Haskett, D., Jensen, R. K., Marchand, A. A., Tomkins-Lane, C., O'Shaughnessy, J., Passmore, S., Schneider, M. J., Shipka, P., Stewart, G., Stuber, K., Yee, A., Ornelas, J.

Lumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is increasingly common with an aging population and can be associated with significant symptoms and functional limitations. We developed this guideline to present the evidence and provide clinical recommendations on nonsurgical management of patients with LSS causing NC. Using the GRADE approach, a multidisciplinary guidelines panel based recommendations on evidence from a systematic review of randomized controlled trials and systematic reviews published through June 2019, or expert consensus. The literature monitored up to October 2020. Clinical outcomes evaluated included pain, disability, quality of life, and walking capacity. The target audience for this guideline includes all clinicians, and the target patient population includes adults with LSS (congenital and/or acquired, lateral recess or central canal, with or without low back pain, with or without spondylolisthesis) causing NC. The guidelines panel developed 6 recommendations based on randomized controlled trials and 5 others based on professional consensus, summarized in 3 overarching recommendations: (Grade: statements are all conditional/weak recommendations) Recommendation 1. For patients with LSS causing NC, clinicians and patients may initially select multimodal care nonpharmacological therapies with education, advice and lifestyle changes, behavioral change techniques in conjunction with home exercise, manual therapy, and/or rehabilitation (moderate-quality evidence), traditional acupuncture on a trial basis (very low-quality evidence), and postoperative rehabilitation (supervised program of exercises and/or educational materials encouraging activity) with cognitive-behavioral therapy 12 weeks postsurgery (low-quality evidence). Recommendation 2. In patients LSS causing NC, clinicians and patients may consider a trial of serotonin-norepinephrine reuptake inhibitors or tricyclic antidepressants. (very low-quality evidence). Recommendation 3. For patients LSS causing NC, we recommend against the use of the following pharmacological therapies: nonsteroidal anti-inflammatory drugs, methylcobalamin, calcitonin, paracetamol, opioids, muscle relaxants, pregabalin (consensus-based), gabapentin (very low-quality), and epidural steroidal injections (high-quality evidence). PERSPECTIVE: This guideline, on the basis of a systematic review of the evidence on the nonsurgical management of lumbar spine stenosis, provides recommendations developed by a multidisciplinary expert panel. Safe and effective non-surgical management of lumbar spine stenosis should be on the basis of a plan of care tailored to the individual and the type of treatment involved, and multimodal care is recommended in most situations.

Keywords 
Lumbar Spinal Stenosis Neurogenic Claudication Clinical symptoms guideline

Anticraving medication for moderate to severe alcohol use disorder

Author/s: 
Mong, J., Ahamad, K., Bach, P.

Alcohol use disorder is characterized by compulsive use, lack of control and harmful consequences of alcohol. Men who have had more than 5 standard drinks and women who have had more than 4 standard drinks on 1 occasion within the past year should be assessed for alcohol use disorder.1 Anticraving medications can play an effective role in overcoming moderate to severe alcohol use disorder and can be prescribed by primary care physicians.

Keywords 
anticraving alcoholsim harm reduction medication craving

Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228

Author/s: 
McDonagh, MS, Selph, SS, Buckley, DI, Holmes, RS, Mauer, K, Ramirez, S, Hsu, FC, Dana, T, Fu, R, Chou

Objectives. To evaluate the effectiveness and comparative effectiveness of nonopioid pharmacologic agents in patients with specific types of chronic pain, considering effects on pain, function, quality of life, and adverse events.

Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, PsycINFO®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) through September 10, 2019, reference lists, data requests, and previous reviews.

Review methods. Randomized controlled trials (RCTs) of nonopioid pharmacologic agents in patients with chronic pain were selected using predefined criteria and dual review. This review focused on seven common chronic pain conditions (neuropathic pain, fibromyalgia, osteoarthritis, inflammatory arthritis, low back pain, chronic headache, sickle cell disease), with effects analyzed at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months). Magnitude of effects were described as small, moderate, or large using previously defined criteria, and strength of evidence was assessed. Meta-analyses were conducted where data allowed, stratified by duration within each intervention type, using random effects models. We evaluated effect modification through subgroup and sensitivity analyses, including specific drug, dose, study quality, and pain type.

Results. We included 185 RCTs in 221 publications and 5 systematic reviews. In the short term, anticonvulsants (pregabalin, gabapentin, and oxcarbazepine for neuropathic pain, pregabalin/gabapentin for fibromyalgia), serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants (duloxetine for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain, milnacipran for fibromyalgia), and nonsteroidal anti-inflammatory drugs (NSAIDs) (for osteoarthritis and inflammatory arthritis) were associated with mostly small improvements (e.g., 5 to 20 points on a 0 to 100 scale) in pain and function. Function was not found to be improved with duloxetine for low back pain or pregabalin/gabapentin for neuropathic pain. Moderate improvement in quality of life was seen with duloxetine in patients with neuropathic pain, and small improvements in patients with osteoarthritis, but evidence was insufficient to draw conclusions for other drugs and conditions. While most comparisons of drugs and doses did not identify differences, diclofenac improved pain and function moderately more than celecoxib. In the intermediate term, limited evidence (1 RCT) showed memantine moderately improved pain, function, and quality of life in patients with fibromyalgia; improvements in pain, but not function, were maintained in the intermediate term with duloxetine and milnacipran for fibromyalgia. Other drugs studied, including acetaminophen (osteoarthritis), capsaicin (neuropathic pain), cannabis (neuropathic pain), amitriptyline (fibromyalgia, neuropathic pain), and cyclobenzaprine (fibromyalgia) had no clear effects. Withdrawal from study due to adverse events was significantly increased with nonopioid drugs, with the greatest increase over placebo seen with cannabis. Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness). Dose viii reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.

Conclusions. In the short term, small improvements in pain and/or function were seen with SNRI antidepressants for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain; pregabalin/gabapentin for neuropathic pain and fibromyalgia; oxcarbazepine for neuropathic pain; and NSAIDs for osteoarthritis and inflammatory arthritis. Improvement in function was not found with duloxetine for low back pain and pregabalin/gabapentin for neuropathic pain. Intermediate- and long-term outcomes were mostly not assessed. Increased incidence of drug class–specific adverse events led to withdrawal from treatment in some patients, suggesting that careful consideration of patient characteristics is needed in selecting nonopioid drug treatments.

Keywords 
chronic pain non-opioid treatment anticonvulsants serotonin-norepinephrine reuptake inhibitor nonsteroidal anti-inflammatory drugs NSAID SNRI cannabis

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial

Author/s: 
Anton, R.F., Latham, P., Voronin, K., Book, S., Hoffman, M., Bristol, E., Prisciandaro, J.

OBJECTIVE: 

To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcoholwithdrawal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: 

This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawalcriteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.

INTERVENTIONS: 

Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each).

MAIN OUTCOMES AND MEASURES: 

The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms.

RESULTS: 

Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.

CONCLUSIONS AND RELEVANCE: 

These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.

TRIAL REGISTRATION: 

ClinicalTrials.gov Identifier: NCT02349477.

Gabapentin for Chronic Neuropathic Pain in Adults

Author/s: 
Wiffen, Phillip J., Derry, Sheena, Bell, Rae F., Rice, Andrew S.C., Tölle, Thomas Rudolf, Phillips, Tudor, Moore, R. Andrew

BACKGROUND:

Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011, 2005 and 2000.

OBJECTIVES:

To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.

SEARCH METHODS:

For this update we searched CENTRAL), MEDLINE, and Embase for randomised controlled trials from January 2014 to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trials registries.

SELECTION CRITERIA:

We included randomised, double-blind trials of two weeks' duration or longer, comparing gabapentin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.

DATA COLLECTION AND ANALYSIS:

Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). We performed a pooled analysis for any substantial or moderate benefit. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.

MAIN RESULTS:

We included four new studies (530 participants), and excluded three previously included studies (126 participants). In all, 37 studies provided information on 5914 participants. Most studies used oral gabapentin or gabapentin encarbil at doses of 1200 mg or more daily in different neuropathic pain conditions, predominantly postherpetic neuralgia and painful diabetic neuropathy. Study duration was typically four to 12 weeks. Not all studies reported important outcomes of interest. High risk of bias occurred mainly due to small size (especially in cross-over studies), and handling of data after study withdrawal.In postherpetic neuralgia, more participants (32%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (17%) (RR 1.8 (95% CI 1.5 to 2.1); NNT 6.7 (5.4 to 8.7); 8 studies, 2260 participants, moderate-quality evidence). More participants (46%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (25%) (RR 1.8 (95% CI 1.6 to 2.0); NNT 4.8 (4.1 to 6.0); 8 studies, 2260 participants, moderate-quality evidence).In painful diabetic neuropathy, more participants (38%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (21%) (RR 1.9 (95% CI 1.5 to 2.3); NNT 5.9 (4.6 to 8.3); 6 studies, 1277 participants, moderate-quality evidence). More participants (52%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (37%) (RR 1.4 (95% CI 1.3 to 1.6); NNT 6.6 (4.9 to 9.9); 7 studies, 1439 participants, moderate-quality evidence).For all conditions combined, adverse event withdrawals were more common with gabapentin (11%) than with placebo (8.2%) (RR 1.4 (95% CI 1.1 to 1.7); NNH 30 (20 to 65); 22 studies, 4346 participants, high-quality evidence). Serious adverse events were no more common with gabapentin (3.2%) than with placebo (2.8%) (RR 1.2 (95% CI 0.8 to 1.7); 19 studies, 3948 participants, moderate-quality evidence); there were eight deaths (very low-quality evidence). Participants experiencing at least one adverse event were more common with gabapentin (63%) than with placebo (49%) (RR 1.3 (95% CI 1.2 to 1.4); NNH 7.5 (6.1 to 9.6); 18 studies, 4279 participants, moderate-quality evidence). Individual adverse events occurred significantly more often with gabapentin. Participants taking gabapentin experienced dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).

AUTHORS' CONCLUSIONS:

Gabapentin at doses of 1800 mg to 3600 mg daily (1200 mg to 3600 mg gabapentin encarbil) can provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is very limited. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. Around 3 or 4 out of 10 participants achieved this degree of pain relief with gabapentin, compared with 1 or 2 out of 10 for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief but may experience adverse events. Conclusions have not changed since the previous update of this review.

Keywords 
neuralgia neuropathic pain gabapentin
Subscribe to gabapentin