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Research · Medication

Gabapentinoids

Cochrane reviews found gabapentin and pregabalin gave at least 50% pain relief to about a third of people with shingles nerve pain, against about a sixth on placebo. Trials found no benefit for sciatica or chronic low back pain. Dizziness and sleepiness affected a fifth to a third. FDA warns of serious breathing problems with opioids or lung disease.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Gabapentin is FDA-approved for postherpetic neuralgia in adults and as add-on treatment for partial onset seizures. It is not a federally scheduled drug. Pregabalin is FDA-approved for nerve pain from diabetic neuropathy, postherpetic neuralgia, spinal cord injury, for fibromyalgia, and as add-on treatment for partial-onset seizures, and is a Schedule V controlled substance. Back pain, sciatica, anxiety, sleep, alcohol use and hot flashes are off-label uses.
Also called
gabapentin, Neurontin, Gralise, gabapentin enacarbil, Horizant, pregabalin, Lyrica, Lyrica CR, gabapentinoid, nerve pain medicine
Taken for
nerve pain, shingles pain, diabetic nerve pain, fibromyalgia, seizures, back pain, sciatica, anxiety, sleep, alcohol cravings, hot flashes, pain after surgery

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help7

Reported risks15

What people take it for, and what was found

Shown to help7

StrongVery common

Nerve pain after shingles

Shown to give at least 50% pain relief to about 32% of people with postherpetic neuralgia, against 13% to 17% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
With gabapentin at 1,200 mg a day or more, 32% had substantial benefit against 17% on placebo (RR 1.8, 95% CI 1.5 to 2.1, number needed to treat 6.7), and 46% had moderate benefit against 25% (number needed to treat 4.8) [1]. With pregabalin 300 mg a day, 32% had at least 50% pain reduction against 13% on placebo (RR 2.5, 95% CI 1.9 to 3.4, number needed to treat 5.3). With 600 mg a day it was 41% against 15% (RR 2.7, 95% CI 2.0 to 3.5, number needed to treat 3.9) [2].
Population
2,260 participants in 8 gabapentin studies of 4 to 12 weeks [1]; 713 and 732 participants in 4 pregabalin studies at each dose [2].
Sources
[1], [2]
Caveats
Both reviews rated the evidence moderate quality. Most people did not reach 50% relief on either drug.
StrongVery common

Diabetic nerve pain

Shown to give at least 50% pain relief to 38% on gabapentin against 21% on placebo, and to 31% on pregabalin 300 mg against 24%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
With gabapentin at 1,200 mg a day or more, 38% had substantial benefit against 21% on placebo (RR 1.9, 95% CI 1.5 to 2.3, number needed to treat 5.9), and 52% had moderate benefit against 37% (number needed to treat 6.6) [1]. With pregabalin 300 mg a day, 31% had at least 50% pain reduction against 24% on placebo (RR 1.3, 95% CI 1.2 to 1.5), and 47% had at least 30% reduction against 42% (number needed to treat 22). With 600 mg a day, 41% had at least 50% reduction against 28% (RR 1.4, 95% CI 1.2 to 1.7, number needed to treat 7.8) [2].
Population
1,277 participants in 6 gabapentin studies [1]; 2,931 participants in 11 studies of pregabalin 300 mg and 1,015 in 5 studies of 600 mg [2].
Sources
[1], [2]
Caveats
Gabapentin is not FDA-approved for diabetic nerve pain. The pregabalin effect at 300 mg was small, and the 600 mg evidence was rated low quality. The review found an absence of efficacy for pregabalin in HIV neuropathy [2].
ModerateVery common

Fibromyalgia

Shown to give at least 50% pain relief to about 22% to 24% of people with fibromyalgia on pregabalin, against about 14% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
With pregabalin 300 to 600 mg a day, about 22% to 24% had at least 50% pain reduction after 12 or 13 weeks against about 14% on placebo, and 39% to 43% had at least 30% reduction against about 28%. Numbers needed to treat ranged from 7 to 14 [3]. For gabapentin, one 12-week trial found at least 30% pain reduction in 49% (38 of 75) against 31% (23 of 75) on placebo, and the reviewers judged the evidence insufficient to support or refute a benefit [4].
Population
3,283 participants in 5 pregabalin trials of 8 to 13 weeks [3]; 150 participants in one gabapentin trial [4].
Sources
[3], [4]
Caveats
The evidence is for pregabalin, rated high quality. The gabapentin trial was rated very low quality, and gabapentin is not approved for fibromyalgia. About 9 in 100 people gained substantial benefit beyond placebo.
StrongVery common

Partial seizures, added to other seizure medicine

Shown to about double the share of people with drug-resistant focal epilepsy whose seizures fell by half, for both gabapentin and pregabalin as add-on treatment.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Added to other seizure medicine, gabapentin raised the chance of a 50% or greater fall in seizure frequency (RR 1.89, 95% CI 1.40 to 2.55), with 25.3% responding at 1,800 mg a day against 9.7% on placebo [5]. Pregabalin raised it by a similar amount (RR 1.95, 95% CI 1.40 to 2.72) and was associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37). The odds of response doubled from 300 mg to 600 mg a day. In one head-to-head trial, response did not differ between pregabalin and gabapentin (RR 0.96, 95% CI 0.82 to 1.12) [6].
Population
1,206 participants in 6 gabapentin trials [5]; 2,663 participants in 9 placebo-controlled pregabalin trials [6].
Sources
[5], [6]
Caveats
Certainty was rated low to moderate. People left pregabalin treatment for adverse effects more often than placebo (RR 2.60, 95% CI 1.86 to 3.64) [6].
Strong

Anxiety

Shown to reduce symptoms of generalized anxiety disorder more than placebo on pregabalin, by about 2.8 points on the Hamilton anxiety scale.

The numbers and sources
Effect
Across 8 trials, pregabalin reduced anxiety symptoms more than placebo (Hedges' g 0.37, 95% CI 0.30 to 0.44), with no difference in dropout rates [11]. In a network meta-analysis, pregabalin lowered Hamilton anxiety scores by 2.79 points more than placebo (95% credible interval 1.91 to 3.69), and was among the better-tolerated drugs in the analysis [12]. A further review found a consistent but not universal effect of gabapentinoids across anxiety conditions, and that pregabalin (SMD -0.55, 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92, 95% CI -1.32 to -0.52) reduced anxiety before surgery [13].
Population
2,299 participants in 8 trials [11]; 25,441 patients in 89 trials of 22 drugs [12]; 55 double-blind trials across bipolar disorder, anxiety and insomnia [13].
Sources
[11], [12], [13]
Caveats
Not an FDA-approved use for either drug. The generalized anxiety evidence is for pregabalin. For gabapentin the evidence is mainly from anxiety before surgery [13].
ModerateVery common

Alcohol use disorder

Shown to reduce the percentage of heavy drinking days on gabapentin in adults with alcohol use disorder, with other drinking outcomes not clearly different from placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In a meta-analysis of 7 trials, every drinking outcome leaned toward gabapentin, but only the percentage of heavy drinking days showed clear benefit (g -0.64, 95% CI -1.22 to -0.06) [15]. In a randomized trial, 27% on gabapentin had no heavy drinking days against 9% on placebo (number needed to treat 5.4), and 18% against 4% were abstinent (number needed to treat 6.2). The benefit appeared in people with more alcohol withdrawal symptoms before the trial and not in those with fewer [16].
Population
7 randomized trials [15]; 90 evaluable adults with alcohol use disorder and a history of withdrawal symptoms, mean age 49.6 [16].
Sources
[15], [16]
Caveats
Not an approved use. The evidence is for gabapentin. See the misuse block below.
ModerateStudied in women

Hot flashes

Shown to reduce the frequency and duration of menopausal hot flashes more than placebo on gabapentin, across seven trials.

The numbers and sources
Effect
Women on gabapentin reported a greater reduction than placebo in hot flash frequency (SMD 2.99, 95% CI 2.01 to 3.98), duration (SMD 0.89, 95% CI 0.49 to 1.30) and composite score (SMD 2.31, 95% CI 1.50 to 3.11). Dizziness and unsteadiness were more frequent on gabapentin [17].
Population
Postmenopausal women in 7 placebo-controlled trials [17].
Sources
[17]
Caveats
Not an approved use. The evidence is for gabapentin, from one meta-analysis that does not report the change in number of hot flashes a day in its abstract.

Mixed results2

Limited

Nerve pain after spinal cord injury

Limited evidence: two trials behind pregabalin's approval found lower pain scores than placebo, while a Cochrane review judged the evidence in central nerve pain inadequate.

The numbers and sources
Effect
The pregabalin label describes two placebo-controlled trials in spinal cord injury pain. In the 12-week trial, 150 to 600 mg a day improved the weekly mean pain score and raised the share of people with at least 30% and 50% pain reduction [7]. A Cochrane review of pregabalin concluded that evidence of efficacy in central neuropathic pain was inadequate [2].
Population
Adults with spinal cord injury pain lasting at least three months, with a baseline pain score of 6.5 to 6.7 out of 10 [7].
Sources
[7], [2]
Caveats
The label text read here gives no effect sizes. The evidence is for pregabalin.
Moderate

Sleep

Mixed results: gabapentin improved sleep measures in people with medical illness in one meta-analysis, while a review of trials in insomnia called the results inconclusive.

The numbers and sources
Effect
In people with sleep disturbance alongside a medical illness, gabapentin beat placebo on five of six composite sleep endpoints, for example SMD 0.50 (95% CI 0.28 to 0.71) on one. People on gabapentin left treatment more often (RR 1.38, 95% CI 1.08 to 1.76), at an average dose of about 1,800 mg a day [14]. A systematic review of gabapentin and pregabalin for insomnia found inconclusive results and minimal evidence [13].
Population
4,684 participants in 26 studies of people with medical illness [14]; trials of gabapentinoids in insomnia [13].
Sources
[14], [13]
Caveats
Not an approved use. The positive analysis was in people whose poor sleep came with another illness, and its authors asked for trials in primary sleep disorders [14].

Not shown to help2

Strong

Sciatica and low back pain

Not shown to reduce leg pain from sciatica or chronic low back pain against placebo, in one large trial and two meta-analyses.

The numbers and sources
Effect
In a trial of pregabalin for sciatica, leg pain at week 8 scored 3.7 on pregabalin and 3.1 on placebo (adjusted difference 0.5, 95% CI -0.2 to 1.2), and at week 52 it was 3.4 against 3.0. No secondary outcome differed, and there were 227 adverse events on pregabalin against 124 on placebo [8]. A meta-analysis found high-quality evidence of no effect of gabapentinoids on chronic low back pain in the short term (mean difference -0.0, 95% CI -0.8 to 0.7) or on lumbar radicular pain (mean difference -0.1, 95% CI -0.7 to 0.5) [9]. A second meta-analysis found gabapentin gave minimal improvement in chronic low back pain against placebo, and that pregabalin did worse than other analgesics [10].
Population
209 patients with sciatica followed for a year [8]; 859 participants in 9 trials [9]; 8 trials, with 185 participants in the gabapentin comparison [10].
Sources
[8], [9], [10]
Caveats
Not an approved use. Evidence quality was very low in [10], and high for the main comparisons in [9].
Moderate

Pain after surgery

Not shown to reduce pain after surgery by a clinically meaningful amount: scores were 3 to 10 points lower on a 100-point scale across 281 trials.

The numbers and sources
Effect
Gabapentinoids given around surgery lowered pain intensity on a 100-point scale by 10 points at 6 hours, 9 at 12 hours, 7 at 24 hours and 3 at 48 hours, each below the 10-point threshold for a meaningful difference. There was no effect at 72 hours or on later chronic pain. Nausea and vomiting were less frequent, and dizziness and visual disturbance more frequent [18].
Population
24,682 participants in 281 trials [18].
Sources
[18]
Caveats
Not an approved use. Results were the same for gabapentin and pregabalin.

Doses studied

The gabapentin label describes 900 mg a day reached over three days for postherpetic neuralgia, raised up to 1,800 mg a day, and notes that trials used 1,800 to 3,600 mg a day without added benefit above 1,800 mg. For seizures in people aged 12 and over it describes 300 to 600 mg three times a day [19]. The pregabalin label gives 150 to 300 mg a day for diabetic nerve pain and postherpetic neuralgia and 300 to 450 mg a day for fibromyalgia. Both drugs are cleared by the kidneys, and both labels give lower doses for reduced kidney function [7][19].

The Cochrane pain reviews pooled gabapentin at 1,200 mg a day or more [1] and pregabalin at 150, 300 and 600 mg a day [2]. The sleep meta-analysis reported an average gabapentin dose of about 1,800 mg a day [14]. The fibromyalgia trial of gabapentin went up to 2,400 mg a day [4].

Risks

Reported risks14

StrongVery common

Dizziness and sleepiness

Shown to cause dizziness in 28% to 30% against 8% on placebo, and sleepiness in 21% to 23% against 5% to 8%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In postherpetic neuralgia trials of gabapentin, dizziness was reported by 28% against 8% on placebo and sleepiness by 21% against 5%. In epilepsy trials it was sleepiness 19% against 9%, dizziness 17% against 7% and unsteadiness 13% against 6%. The label states that driving studies with a gabapentin prodrug indicate gabapentin may cause significant driving impairment [19]. In pregabalin trials, dizziness was reported by 30% against 8% and sleepiness by 23% against 8%, more often at higher doses, and each led 4% to stop [7]. In the Cochrane review of pregabalin for postherpetic neuralgia, dizziness affected 29% on 300 mg and 35% on 600 mg against 8% to 9% on placebo [2]. In postherpetic neuralgia trials, 16% on gabapentin and 9% on placebo stopped because of an adverse reaction [19].
Population
336 people on gabapentin and 227 on placebo in two postherpetic neuralgia trials, and people over 12 in epilepsy trials [19]; adults in pregabalin controlled trials [7]; 45 studies with 11,906 participants [2].
Sources
[19], [7], [2]
Caveats
Among people who reported these effects in short pregabalin trials, dizziness lasted to the final dose in 30% and sleepiness in 42% [7].
StrongCommon

Swelling and weight gain

Shown to cause swelling of the legs or hands in 6% to 8% against 2% on placebo, and weight gain of 7% or more in 9% against 2% on pregabalin.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In pregabalin trials, peripheral edema was reported by 6% against 2% on placebo, and a gain of 7% or more of body weight within 14 weeks by 9% against 2%. Weight gain was related to dose and length of exposure. Among people with diabetes, those on pregabalin gained an average of 1.6 kg against 0.3 kg on placebo. In people taking a thiazolidinedione diabetes drug, edema was reported by 3% on that drug alone, 8% on pregabalin alone and 19% on both [7]. In postherpetic neuralgia trials of gabapentin, peripheral edema was reported by 8% against 2% and weight gain by 2% against 0 [19].
Population
Adults in controlled pregabalin trials of up to 14 weeks [7]; 336 people on gabapentin and 227 on placebo [19].
Sources
[7], [19]
Caveats
The label states that the long-term cardiovascular effects of weight gain on pregabalin are unknown [7].
ModerateCommon

Misuse

Linked to misuse in about 1% of the general population and 15% to 22% of people who abuse opioids, in a systematic review of gabapentin.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A systematic review put gabapentin misuse at 1% in the general population, 40% to 65% among people with prescriptions and 15% to 22% among people who abuse opioids. People with a history of drug abuse were most often involved [22]. A later review of 55 studies found opioid use disorder was the greatest risk factor and reported growing evidence of harm, including more hospital use and higher risk of opioid-related overdose death [23]. In pregabalin trials of over 5,500 people, euphoria was reported as an adverse reaction by 4% against 1% on placebo. In 15 recreational users of sedative drugs, a single 450 mg dose was rated for liking and high at a level similar to diazepam 30 mg [7]. The gabapentin label states that misuse and abuse have been reported, mostly in people with a history of polysubstance abuse, and that its abuse potential has not been evaluated in human studies [19].
Population
Epidemiological studies and case reports of gabapentin [22]; 55 studies, 46 of them observational [23]; over 5,500 people in pregabalin trials [7].
Sources
[22], [23], [7], [19]
Caveats
The band above is the rate of euphoria in pregabalin trials. Misuse figures come from surveys and special populations with varied definitions.
ModerateCommon

Blurred vision

Shown to cause blurred vision in 7% on pregabalin against 2% on placebo, which resolved with continued dosing in most cases.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In controlled trials, blurred vision was reported by 7% on pregabalin and 2% on placebo, and under 1% stopped treatment for vision-related events [7]. In trials of gabapentin for chronic low back pain, visual disturbances were more frequent than on placebo (RR 5.72, 95% CI 1.94 to 16.91) [10].
Population
Adults in controlled pregabalin trials [7]; 3 gabapentin trials in chronic low back pain [10].
Sources
[7], [10]
Caveats
The gabapentin estimate comes from small trials with a wide interval.
ModerateStudied in childrenCommon

Mood and behavior changes in children on gabapentin

Shown to cause emotional lability in 6% against 1.3% on placebo and hostility in 5.2% against 1.3% in children aged 3 to 12 with epilepsy.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In controlled epilepsy trials in children aged 3 to 12, emotional lability was reported by 6% on gabapentin against 1.3% on placebo, hostility including aggressive behavior by 5.2% against 1.3%, hyperkinesia by 4.7% against 2.9% and thought disorder, including concentration problems, by 1.7% against 0. Most reactions were mild to moderate [19].
Population
Children aged 3 to 12 with epilepsy in controlled trials [19].
Sources
[19]
Caveats
The evidence is for gabapentin in children with epilepsy.
ModerateUncommon

Suicidal thoughts and behavior

FDA states antiepileptic drugs as a class raised suicidal thoughts or behavior to 0.43% against 0.24% on placebo, about one extra case per 530 people treated.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In pooled analyses of 199 placebo-controlled trials of 11 antiepileptic drugs, suicidal thinking or behavior occurred in 0.43% of 27,863 people on a drug and 0.24% of 16,029 on placebo (adjusted relative risk 1.8, 95% CI 1.2 to 2.7) [19]. In a Swedish cohort comparing periods on and off treatment in the same people, gabapentinoid treatment was associated with suicidal behavior and death from suicide (HR 1.26, 95% CI 1.20 to 1.32). Taken separately, pregabalin was associated with increased hazards, and gabapentin with decreased or no significant hazards [24].
Population
43,892 people in 199 trials with a median length of 12 weeks [19]; a Swedish cohort of people prescribed gabapentinoids, of whom 10,026 (5.2%) were treated for suicidal behavior or died from suicide [24].
Sources
[19], [24]
Caveats
The pooled trials cover 11 antiepileptic drugs, not gabapentin or pregabalin alone. The cohort is observational, and its increased hazards were concentrated in people aged 15 to 24 [24].
LimitedHow often is not known

FDA warning: serious breathing problems

FDA states serious breathing difficulties may occur in people taking gabapentin or pregabalin who also use opioids or other sedating drugs, or have reduced lung function.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In 2019 FDA warned that serious breathing difficulties may occur in people using gabapentinoids who have respiratory risk factors: use of opioids or other drugs that depress the central nervous system, conditions such as chronic obstructive pulmonary disease, and older age. FDA required new label warnings and required manufacturers to run trials of abuse potential, particularly in combination with opioids [20]. Both labels now state that case reports, human studies and animal studies associate the drug with serious, life-threatening or fatal respiratory depression when taken with central nervous system depressants, including opioids, or with underlying respiratory impairment [19][7].
Population
Case reports and studies reviewed by FDA [20].
Sources
[20], [19], [7]
Caveats
The warning rests largely on case reports, with no rate. This is not a boxed warning.
LimitedHow often is not known

Use with opioids

Linked to about 49% higher odds of opioid-related death when gabapentin was prescribed alongside an opioid, in one case-control study of opioid users.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among people prescribed opioids in Ontario, 12.3% of those who died of an opioid-related cause (155 of 1,256) and 6.8% of matched controls (313 of 4,619) had been prescribed gabapentin in the previous 120 days. After adjustment, the combination was associated with higher odds of opioid-related death than an opioid alone (adjusted OR 1.49, 95% CI 1.18 to 1.88), rising to about 1.6 at moderate and high gabapentin doses [21]. The gabapentin label reports respiratory depression and sedation, sometimes resulting in death, with opioids such as morphine, hydrocodone, oxycodone and buprenorphine. It states that morphine raises gabapentin levels and that gabapentin lowers hydrocodone exposure [19].
Population
1,256 cases and 4,619 controls among opioid users, 1997 to 2013 [21].
Sources
[21], [19]
Caveats
Observational. The study gives odds among people already taking opioids, not an absolute rate. The evidence is for gabapentin.
LimitedHow often is not known

Alcohol and other sedating drugs

The label reports additive effects on thinking and coordination when pregabalin was taken with alcohol, lorazepam or oxycodone, with no important effect on breathing in that study.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In a study of repeated doses of pregabalin given with oxycodone, lorazepam or ethanol, no change in drug levels was seen, while effects on cognitive and gross motor functioning added together. No clinically important effects on respiration were seen [7].
Population
Volunteers in an interaction study summarized in labeling without counts [7].
Sources
[7]
Caveats
The label gives no numbers. The evidence is for pregabalin.
LimitedHow often is not known

Antacids and gabapentin

The label reports that an antacid containing aluminum and magnesium hydroxides lowered the amount of gabapentin absorbed by about 20%.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Mean bioavailability of gabapentin fell by about 20% when it was taken with an aluminum and magnesium hydroxide antacid. The label also states that gabapentin does not interfere with the metabolism of other common seizure medicines [19]. The pregabalin label states that pregabalin is unlikely to be involved in significant pharmacokinetic interactions [7].
Population
Interaction studies summarized in labeling [19].
Sources
[19], [7]
Caveats
A change in absorption, with no rate of harm. The evidence is for gabapentin.
LimitedHow often is not known

Symptoms after stopping

The label reports insomnia, nausea, headache, anxiety, sweating and diarrhea after abrupt or rapid stopping of pregabalin, and more seizures in people with epilepsy. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The pregabalin label states that some people reported insomnia, nausea, headache, anxiety, hyperhidrosis and diarrhea after abrupt or rapid discontinuation, which it describes as consistent with physical dependence, and that seizure frequency may rise in people with seizure disorders [7]. The gabapentin label describes rare postmarketing reports of agitation, disorientation and confusion shortly after stopping doses above the labeled range, and states that the dependence potential of gabapentin has not been evaluated in human studies [19].
Population
Clinical study and postmarketing reports summarized in labeling [7][19].
Sources
[7], [19]
Caveats
Neither label gives the share of people affected.
LimitedHow often is not known

Accidental overdose, injuries and road incidents

Linked to more unintentional overdoses, injuries and road traffic incidents during treatment periods in one Swedish cohort, driven by pregabalin.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Comparing periods on and off treatment in the same people, gabapentinoid treatment was associated with unintentional overdose (HR 1.24, 95% CI 1.19 to 1.28), head or body injuries (HR 1.22, 95% CI 1.19 to 1.25) and road traffic incidents or offences (HR 1.13, 95% CI 1.06 to 1.20). Arrests for violent crime did not clearly differ (HR 1.04, 95% CI 0.98 to 1.11). Pregabalin was associated with increased hazards of every outcome, and gabapentin with decreased or no significant hazards [24].
Population
A Swedish cohort of people prescribed gabapentinoids, of whom 8.9% had an unintentional overdose and 6.3% a road traffic incident or offence during the study period [24].
Sources
[24]
Caveats
Observational. The percentages are for the whole study period, on or off treatment, so no rate on the drug can be set.
LimitedHow often is not known

Severe allergic reactions

The label warns of angioedema and anaphylaxis with both drugs, and of a multiorgan hypersensitivity reaction with gabapentin that has been fatal. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The gabapentin label states that anaphylaxis and angioedema can occur after the first dose or at any time, and that drug reaction with eosinophilia and systemic symptoms, also called multiorgan hypersensitivity, has occurred, in some cases fatal or life-threatening [19]. The pregabalin label reports postmarketing cases of angioedema with swelling of the face, mouth and throat, some life-threatening [7].
Population
Postmarketing reports summarized in labeling [19][7].
Sources
[19], [7]
Caveats
Reports with no denominator.
LimitedHow often is not known

Heart conduction on pregabalin

The label reports pregabalin lengthened the PR interval on ECG by a mean of 3 to 6 milliseconds, without a rise in heart block.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In analyses of trial ECG data, the mean PR interval rose by 3 to 6 milliseconds at doses of 300 mg a day or more. This was not associated with more people having a PR interval above 200 milliseconds or a 25% rise from baseline, or with more second or third degree heart block [7].
Population
Adults with ECG data in pregabalin trials [7].
Sources
[7]
Caveats
An average change on a tracing, with no count of people affected. The evidence is for pregabalin.

Mixed results1

ModerateCommon

Pregnancy

Not linked to major birth defects after adjustment in two large cohorts, while gabapentin late in pregnancy was linked to preterm birth and small babies.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Of 477 infants exposed to pregabalin in the first trimester, 5.9% had malformations against 3.3% of unexposed infants. After adjustment the relative risk was 1.16 (95% CI 0.81 to 1.67), and 1.02 (95% CI 0.69 to 1.51) pooled for pregabalin taken alone [25]. For gabapentin in the first trimester, the adjusted relative risk was 1.07 for major malformations (95% CI 0.94 to 1.21) and 1.12 for cardiac defects (95% CI 0.89 to 1.40). Exposure both early and late in pregnancy was associated with preterm birth (RR 1.22, 95% CI 1.09 to 1.36), small-for-gestational-age infants (RR 1.32, 95% CI 1.08 to 1.60) and neonatal intensive care admission (RR 1.35, 95% CI 1.20 to 1.52) [26]. Both labels state there are no adequate studies in pregnant women and that the drug caused developmental harm in animals [19][7].
Population
477 pregabalin-exposed infants in US Medicaid data and 174 in a commercial database [25]; 4,642 gabapentin-exposed pregnancies among 1,753,865 [26].
Sources
[25], [26], [19], [7]
Caveats
Observational. The band above is the unadjusted malformation rate in pregabalin-exposed infants, which did not differ significantly from unexposed infants after adjustment. Among women with two or more gabapentin dispensings, cardiac defects were more frequent (RR 1.40, 95% CI 1.03 to 1.90) [26].

Claims tested and not found

  1. That pregabalin relieves sciatica. In 209 patients, leg pain did not differ from placebo at 8 weeks or at 52 weeks, and adverse events were more frequent on pregabalin [8].
  2. That gabapentinoids relieve chronic low back pain. A meta-analysis found high-quality evidence of no effect against placebo in the short term (mean difference -0.0, 95% CI -0.8 to 0.7) [9].
  3. That gabapentin prevents migraine. Pooling four trials, headache frequency did not differ between gabapentin and placebo (mean difference -0.44, 95% CI -1.43 to 0.56) [27].
  4. That gabapentinoids give meaningful pain relief after surgery. Across 281 trials, pain scores were lower by less than the 10-point threshold for a meaningful difference, with no effect on later chronic pain [18].
  5. That pregabalin in early pregnancy causes birth defects. After adjustment, the relative risk of major malformations was 1.16 (95% CI 0.81 to 1.67). The authors could not rule out a small effect [25].

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