pregabalin and Drug-Overdose

Pregabalin is an anticonvulsant widely used for the treatment of epilepsy and neuropathic pain. However, there is a growing concern about its misuse, particularly among drug users and patients with substance use disorders (SUD). It is often used in combination with other psychoactive molecules and at levels well above the recommended doses. Increasing cases of overdose and death associated with the misuse of pregabalin have been reported worldwide. Therefore, raising prescribers' awareness of this scourge is mandatory and the role of the pharmacist is crucial in reducing this phenomenon.

Topics: Anticonvulsants; Drug Overdose; Gabapentin; Humans; Pregabalin; Substance-Related Disorders

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).

Topics: Drug Overdose; Frailty; Gabapentin; Humans; Poisoning; Pregabalin; Renal Dialysis

A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially.. Update previous SR and describe new insights regarding gabapentinoid abuse.. A SR of PubMed was conducted to identify studies published from 7/29/2016-8/31/2020. Four searches were performed using the following terms: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid" AND one of the following substance misuse/abuse-related terms: "substance-related disorders [MeSH]", "overdose", "abuse", or "misuse". Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded.. Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid-related overdose mortality risk.. Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.

Topics: Animals; Drug Overdose; Gabapentin; Humans; Pregabalin

This article will review the epidemiology and pharmacology of gabapentinoids (gabapentin and pregabalin) relevant to their emerging misuse potential and provide guidance for clinical and regulatory management. Gabapentinoids are γ-aminobutyric acid analogues that produce their therapeutic effects by inhibiting voltage-gated calcium channels and decreasing neurotransmitter release. Recently gabapentinoid prescribing and use have increased tremendously. Although traditionally thought to possess a favorable safety profile, gabapentinoid misuse has also risen significantly. Gabapentinoid misuse generally occurs in combination with other substances, most notably opioids, and may be for purposes of eliciting euphoric effects, enhancing the effects of other substances, or self-treating conditions such as withdrawal, pain, anxiety, or insomnia. Given its faster onset, increased bioavailability and potency, and nonsaturable absorption, pregabalin's pharmacokinetics theoretically enhance its misuse liability versus gabapentin. However, gabapentin can produce similar euphoric effects, and epidemiologic studies have identified higher rates of gabapentin misuse in the United States, likely because of greater availability and less regulated prescribing. Although adverse events of gabapentinoid-only ingestion are relatively benign, a growing body of evidence indicates that gabapentinoids significantly increase opioid-related morbidity and mortality when used concomitantly. In addition, significant withdrawal effects may occur on abrupt discontinuation. As a result of these trends, several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug-monitoring programs. Although increased regulation of gabapentin prescribing may be warranted, harm reduction efforts and increased patient and provider education are necessary to mitigate this concerning gabapentinoid misuse trend.

Topics: Area Under Curve; Calcium Channel Blockers; Drug Overdose; Gabapentin; Half-Life; Humans; Metabolic Clearance Rate; Pregabalin; Prescription Drug Misuse; Respiratory Insufficiency; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

In the last ten years, gabapentin and pregabalin have been becoming dispensed broadly and sold on black markets, thereby, exposing millions to potential side-effects. Meanwhile, several pharmacovigilance-databases have warned for potential abuse liabilities and overdose fatalities in association with both gabapentinoids. To evaluate their addiction risk in more detail, we conducted a systematic review on PubMed/Scopus and included 106 studies. We did not find convincing evidence of a vigorous addictive power of gabapentinoids which is primarily suggested from their limited rewarding properties, marginal notes on relapses, and the very few cases with gabapentinoid-related behavioral dependence symptoms (ICD-10) in patients without a prior abuse history (N=4). In support, there was no publication about people who sought treatment for the use of gabapentinoids. Pregabalin appeared to be somewhat more addictive than gabapentin regarding the magnitude of behavioral dependence symptoms, transitions from prescription to self-administration, and the durability of the self-administrations. The principal population at risk for addiction of gabapentinoids consists of patients with other current or past substance use disorders (SUD), mostly opioid and multi-drug users, who preferred pregabalin. Pure overdoses of gabapentinoids appeared to be relative safe but can become lethal (pregabalin > gabapentin) in mixture with other psychoactive drugs, especially opioids again and sedatives. Based upon these results, we compared the addiction risks of gabapentin and pregabalin with those of traditional psychoactive substances and recommend that in patients with a history of SUD, gabapentinoids should be avoided or if indispensable, administered with caution by using a strict therapeutic and prescription monitoring.

Topics: Amines; Analgesics; Behavior, Addictive; Cyclohexanecarboxylic Acids; Databases, Bibliographic; Drug Overdose; Gabapentin; gamma-Aminobutyric Acid; Humans; Pregabalin; Self Administration; Substance-Related Disorders

Gabapentinoid (pregabalin and gabapentin) abuse is increasingly being reported.. To assess the extent of gabapentinoid abuse, characteristics of typical abusers, patterns of abuse, and potential harms in order to bring this trend to providers' attention.. A systematic review of MEDLINE, Cochrane Library, ClinicalTrials.gov, and US FDA data, indexed through 28 July 2016, utilizing the following searches: pregabalin OR gabapentin OR gabapentinoid AND one of the following: abuse, misuse, overdose, or substance-related disorders[MESH], was conducted. Additional studies were identified through review of references. English-language epidemiological studies, clinical studies, and case reports/series of gabapentinoid abuse/misuse/overdose were included. The authors reached consensus regarding study inclusion after full-text review. The body of literature was assessed for bias qualitatively.. Fifty-nine studies were included in this systematic review (24 epidemiological, three clinical abuse liability, 16 abuse/misuse/dependence case reports/series, 17 acute overdose case reports/series-one included both an epidemiological study and case series and was included in both counts). Analysis of these studies indicates increasing numbers of patients are self-administering higher than recommended doses to achieve euphoric highs. In the general population, a 1.6% prevalence of gabapentinoid abuse was observed, whereas prevalence ranged from 3% to 68% among opioid abusers. An international adverse event database identified 11,940 reports of gabapentinoid abuse from 2004-2015, with >75% reported since 2012. Risk factors include a history of substance abuse, particularly opioids, and psychiatric co-morbidities. While effects of excessively high doses are generally non-lethal, gabapentinoids are increasingly being identified in post-mortem toxicology analyses.. Evidence suggests gabapentinoids possess potential for abuse, particularly in individuals with a history of opioid abuse, and reports of such abuse are increasingly being documented. Prescribers should be aware of high-risk populations and monitor for signs of abuse.

Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Drug Overdose; Gabapentin; gamma-Aminobutyric Acid; Humans; Pregabalin; Substance-Related Disorders

Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.. We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database.. There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none;. Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Topics: Acetaminophen; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Coma; Diazepam; Droperidol; Drug Overdose; Duloxetine Hydrochloride; Female; Humans; Hypotension; Ibuprofen; Middle Aged; Norepinephrine; Oxycodone; Pregabalin; Quetiapine Fumarate; Seizures; Serotonin; Sympathomimetics; Tachycardia

Gabapentinoids are centrally active GABA agonists whose use has increased substantially in the past decade. The current study aimed to provide a comprehensive clinical profile of a national case series of fatal poisonings related to gabapentinoids.. Retrospective study of all deaths due to drug toxicity in Australia in which gabapentinoids were a contributory mechanism, retrieved from the National Coronial Information System (2000-2020). Information was collected on case characteristics, toxicology and major organ pathology.. A total of 887 cases were identified, with a mean age of 45.7 years and 55.2% being male. Death was due to accidental toxicity in 81.3% of cases and intentional in 18.7%. Pre-existing disease was co-contributory to drug toxicity in 19.5%. Pregabalin was present in 92.9% of cases, with a median blood concentration of 7.6 mg/L (range 0.1-850.0 mg/L). Gabapentin was present in 7.2%, with a median blood concentration of 9.5 mg/L (range 0.5-1940.0 mg/L). Both pregabalin and gabapentin were present in five cases. No other gabapentinoids were detected. Drugs other than gabapentinoids were present in 99.8%, most frequently opioids (90.1%), hypnosedatives (76.9%) and antidepressants (60.5%). A body mass index in the obese range was seen in 45.4%. Clinically significant pre-existing disease was common, notably cardiomegaly (24.9%), emphysema (20.2%), nephrosclerosis (18.7%) and severe hepatic steatosis (11.7%).. The concomitant use of other drugs was close to universal, with CNS depressants predominating. Mental health problems, chronic pain and substance misuse were prominent.

Topics: Analgesics, Opioid; Drug Overdose; Female; Gabapentin; Humans; Male; Middle Aged; Pregabalin; Retrospective Studies

Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths.. All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender.. There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years.. The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.

Topics: Adolescent; Adult; Analgesics; Analgesics, Opioid; Autopsy; Benzodiazepines; Buprenorphine; Drug Overdose; Ethanol; Female; Finland; Humans; Illicit Drugs; Male; Middle Aged; Pregabalin; Risk Factors; Substance-Related Disorders; Young Adult

Post-mortem findings of gabapentinoids have often been connected to drug abuse and especially opioid use. We aimed to investigate whether gabapentinoids have been implicated in the cause of death without the presence of opioids. In a three-year study period from 2016 to 2018, a total of 907 Finnish post-mortem cases positive for pregabalin or gabapentin were found. In nearly half of the pregabalin cases and in a third of the gabapentin cases, the blood concentration was above the typical therapeutic range of the drug. Of the cases in which pregabalin was detected, in 35% the drug was implicated in a fatal poisoning with or without other drugs or alcohol. For gabapentin, the percentage was 22%. In most of the fatal gabapentinoid poisonings, opioids or other central nervous system depressants were additionally detected in relevant concentrations. There were eight non-opioid gabapentinoid poisonings, in which no relevant other drugs were detected. Many of these cases were unintentional poisonings with a relatively high gabapentinoid concentration in the blood. In all but one, the manner of death was accidental, or the intent was undetermined. This study confirmed the previous findings that gabapentinoids are mostly implicated in fatal poisoning together with opioids. Half of the non-opioid cases were related to drug abuse but in the other half the death was presumably caused by overuse of a prescribed drug or suicide. While the use of gabapentinoids is a well-known problem among people who use drugs, it is important to note other groups of users who may be at risk of overdose by gabapentinoids.

Topics: Accidents; Adult; Aged; Aged, 80 and over; Analgesics; Chromatography, Liquid; Drug Overdose; Female; Finland; Forensic Toxicology; Gabapentin; Humans; Male; Mass Spectrometry; Middle Aged; Pregabalin; Retrospective Studies; Suicide, Completed

With rising use worldwide, pregabalin is increasingly implicated in poisoning deaths. We aimed to investigate the clinical effects and complications of pregabalin poisoning.. This is a retrospective review of patients presenting with pregabalin poisoning to two tertiary toxicology units from 1 July 2014 to 30 June 2019. Patients were identified from prospective databases maintained by both units and data were extracted from these in addition to medical records.. There were 488 presentations in 413 patients (237 [57%] male) over the five-year period. The median age was 41 years (IQR 31-50 years). Deliberate self-poisonings accounted for 342 (70%) presentations, with 121 (25%) recreational exposures. Recreational exposures increased over the period from 2 (4%) in the first year to 54 (39%) presentations in the final year. The median dose of pregabalin was 1200 mg (IQR 600-3000 mg, range 75-16 800 mg). Co-ingestions occurred in 427 (88%) presentations, with sedating agents being co-ingested in 387 (79%)-most commonly opioids and benzodiazepines in 201 (41%) and 174 (36%) presentations respectively. Coma (GCS < 9) occurred in 89 (18%) cases, with 52 (11%) patients being intubated. Only one (0.2%) of these patients had not co-ingested a sedating agent. Hypotension occurred in 26 (5%) cases, all with co-ingestants. Seizures occurred in 11 (2%) cases, 3/59 (5%) in pregabalin-only overdoses. The median length of stay was 16.5 hours (IQR 10-25 hours).. Pregabalin overdose does not cause severe toxicity, but rather mild sedation and, uncommonly, seizures. Coma is common in the presence of sedating co-ingestants. Recreational use is increasing.

Topics: Adult; Analgesics, Opioid; Benzodiazepines; Drug Overdose; Female; Humans; Male; Poisoning; Pregabalin; Retrospective Studies

Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of ∼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs.. National data from the Information Service Division, NHS Scotland were analysed for prescribing, sociodemographic, and mortality data from the Health Informatics Centre, University of Dundee. DRDs in which gabapentinoids were implicated were identified from National Records of Scotland and Tayside Drug Death Databases.. From 2006 to 2016, the number of gabapentin prescriptions in Scotland increased 4-fold (164 630 to 694 293), and pregabalin 16-fold (27 094 to 435 490). In 2016 'recurrent users' (three or more prescriptions) had mean age 58.1 yr, were mostly females (62.5%), and were more likely to live in deprived areas. Of these, 60% were co-prescribed an opioid, benzodiazepine, or both (opioid 49.9%, benzodiazepine 26.8%, both 17.1%). The age-standardised death rate in those prescribed gabapentinoids was double that in the Scottish population (relative risk 2.16, 95% confidence interval 2.08-2.25). Increases in gabapentinoids contributing to cause of DRDs were reported regionally and nationally (gabapentin 23% vs 15%; pregabalin 21% vs 7%). In Tayside, gabapentinoids were implicated in 22 (39%) of DRDs, 17 (77%) of whom had not received a prescription.. Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death (including DRDs). Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid; Benzodiazepines; Child; Child, Preschool; Drug Overdose; Drug Therapy, Combination; Female; Gabapentin; Humans; Infant; Male; Middle Aged; Practice Patterns, Physicians'; Pregabalin; Scotland; Sex Factors; Young Adult

Pregabalin is an anticonvulsant and analgesic designed to treat neuropathic pain and partial seizure disorders and has been available in Australia as a prescription medication since 2005. Studies have found high rates of polydrug use associated with pregabalin and it is reportedly used recreationally for its euphoric and relaxing effects as well as to self-manage opioid withdrawal symptoms. A robust analytical method for the analysis of pregabalin using protein precipitation and LC/MS/MS was developed, validated and employed in routine case work. In recent years a substantial increase in pregabalin detections in coronial case submissions had been noted. This study examines the case characteristics and outcomes of 332 coronial cases submitted to the laboratory and analyzed for pregabalin between 2015 and 2017. Pregabalin was identified in approximately 5% of all coronial cases submitted during this time. A high rate of concurrent drug use with pregabalin was evident with the predominant classes being opioids, benzodiazepines and anti-depressants. Post-mortem blood pregabalin concentrations ranged from <0.05 to 140 mg/kg (median 5.5 mg/kg); however, limited interpretation of levels could be achieved as the drug was rarely identified in the absence of other drugs. Cause of death (COD) was found to be drug related in 58% of all cases, with mixed drug toxicity specifically mentioned as related to COD in 40% of cases.

Topics: Analgesics; Anticonvulsants; Australia; Drug Overdose; Forensic Toxicology; Humans; Pregabalin; Substance-Related Disorders

Pregabalin is a gamma-aminobutyric acid (GABA) analogue, used to treat neuropathic pain and epilepsy. Pregabalin was registered in Australia in 2005, and subsidized publically in 2013. We aimed to describe Australian patterns of pregabalin use and intentional poisoning, and identify people potentially at high risk of misuse.. Population-based retrospective cohort study of dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme (July 2012-February 2017); intentional poisoning calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016); intentional poisonings in two Australian toxicology service databases; and poisoning fatalities in NSW coronial records (2005-2016).. A total of 122 572 people dispensed pregabalin, people with intentional pregabalin overdoses managed by NSWPIC and the toxicology services and pregabalin-associated deaths referred to the NSW coroner.. Trends in dispensing, poisoning, death; demographics and patient characteristics, proportion of users at high risk of misuse (latent class analysis, LCA) and characteristics of high-risk users.. Pregabalin dispensing increased by 73 424 per year [95% confidence interval (CI) = 61726-85 121 P < 0.001] between 2013 and 2016. NSWPIC received 1158 reports of intentional pregabalin poisonings, with a 53.8% increase per year, 2005-2016 (95% CI = 44.0-64.2%, P < 0.001). We identified 88 pregabalin-associated deaths, 57.8% yearly increase (95% CI = 30.0-91.6%, P < 0.001). Patients overdosing on pregabalin commonly co-ingested opioids, benzodiazepines and illicit drugs, and had high rates of psychiatric and substance use comorbidities; 14.7% of pregabalin users were classed by the LCA as at high risk of misuse, and were more likely to be younger, male, co-prescribed benzodiazepines or opioids, have more individual prescribers and higher pregabalin strengths dispensed.. There has been a dramatic increase in pregabalin use, poisonings and deaths in Australia since it became subsidized publicly in 2013. One in seven Australians dispensed pregabalin appears to be at high risk of misuse.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid; Australia; Benzodiazepines; Cohort Studies; Drug Overdose; Female; Humans; Male; Mental Disorders; Middle Aged; Pregabalin; Prescription Drug Misuse; Retrospective Studies; Sex Factors; Substance-Related Disorders; Young Adult

To compare changes in pregabalin prescribing and misuse-related ambulance attendances; to characterise the patients attended by paramedics for pregabalin misuse-related harms; to assess the association of pregabalin misuse with use of other sedatives and with suicidal ideation and self-harm; to compare the characteristics of pregabalin misuse-related harms in people who misuse pregabalin according to whether or not they also used other sedatives.. Retrospective analysis of data on ambulance attendances in Victoria, January 2012 - December 2017, for which pregabalin misuse-related harms were a contributing factor.. Rates of pregabalin misuse-related ambulance attendances, pregabalin prescription rates (each 6-monthly); patient characteristics, including age, sex, history of drug misuse or psychiatric problems, concurrent use of other sedatives, and current suicidal ideation and self-harm.. There were 1201 pregabalin misuse-related attendances during the study period; the rate increased from 0.28 cases per 100 000 population in the first half of 2012 to 3.32 cases per 100 000 in the second half of 2017. The attendance rate was strongly correlated with prescription rates in Australia (r = 0.90; P = 0.001). 593 attendances (49%) were for people with a history that may have contraindicated prescribing pregabalin. Pregabalin was frequently misused with other sedatives (812 attendances, 68%), particularly benzodiazepines (440, 37%); 472 attendances (39%) were associated with suicide attempts. People who misused pregabalin with other sedatives more frequently presented with moderate to severe impairments of consciousness, but the frequency of suicide attempts was similar whether other sedatives were concurrently used or not.. Rates of pregabalin misuse-related ambulance attendances in Victoria have increased markedly over the past 6 years. Caution is required when prescribing pregabalin for people taking other sedatives. Limiting the dispensing of this drug may reduce the risks associated with its misuse.

Topics: Adolescent; Adult; Ambulances; Central Nervous System Depressants; Drug Overdose; Female; Humans; Male; Middle Aged; Pregabalin; Retrospective Studies; Self-Injurious Behavior; Victoria; Young Adult

To examine associations between gabapentinoids and adverse outcomes related to coordination disturbances (head or body injuries, or both and road traffic incidents or offences), mental health (suicidal behaviour, unintentional overdoses), and criminality.. Population based cohort study.. High quality prescription, patient, death, and crime registers, Sweden.. 191 973 people from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids (pregabalin or gabapentin) during 2006 to 2013.. Primary outcomes were suicidal behaviour, unintentional overdoses, head/body injuries, road traffic incidents and offences, and arrests for violent crime. Stratified Cox proportional hazards regression was conducted comparing treatment periods with non-treatment periods within an individual. Participants served as their own control, thus accounting for time invariant factors (eg, genetic and historical factors), and reducing confounding by indication. Additional adjustments were made by age, sex, comorbidities, substance use, and use of other antiepileptics.. During the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. When stratifying on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.. This study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

Topics: Accidents, Traffic; Adult; Aged; Drug Overdose; Drug Prescriptions; Female; Follow-Up Studies; Gabapentin; Humans; Male; Middle Aged; Pregabalin; Prescription Drugs; Risk Factors; Suicide; Sweden; Violence; Wounds and Injuries; Young Adult

Reports of gabapentinoid (gabapentin and pregabalin) misuse have increased in recent years. Pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) provides a useful examination of adverse drug event (ADE) reporting for safety signal detection.. This study was conducted to analyze epidemiological information on the nature and extent of gabapentin/pregabalin abuse utilizing the FAERS database.. A query was designed utilizing SafeRx, an indexed, searchable database of FAERS data from October 2012-December 2016. All-cause and abuse-related (including abuse/misuse/dependence/overdose events) ADE reports for gabapentin and pregabalin were isolated, as well as limited demographic data. The proportional reporting ratio (PRR) was calculated to compare signal detection.. A total of 10,038 all-cause ADEs were reported to FAERS for gabapentin, including 576 (5.7%) abuse-related events. For pregabalin, 571 all-cause ADEs were identified, including 58 (10.2%) related to abuse. Compared to all-cause ADEs, those involved in abuse-related events were younger and more likely to be male. The PRR of pregabalin versus gabapentin abuse-related events was 1.77.. Though not traditionally thought of as drugs of abuse, over 600 cases of gabapentinoid abuse were reported in the time frame analyzed, prompting the need for further study and regulatory investigation.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Analgesics; Anticonvulsants; Databases, Factual; Drug Overdose; Female; Gabapentin; Humans; Male; Middle Aged; Pharmacovigilance; Pregabalin; Substance-Related Disorders; United States; United States Food and Drug Administration; Young Adult

Intentional drug overdose (IDO) is a significant public health problem. Concerns about the misuse of gabapentinoids, i.e. pregabalin and gabapentin, including their consumption in IDO have grown in recent years. This paper examines the trends in the prevalence of gabapentinoids taken in IDO, the profile of individuals taking them, and associated overdose characteristics.. Presentations to emergency departments involving IDO, recorded by the National Self-Harm Registry Ireland between 1 January 2007 and 31 December 2015 were examined. Data items included patient demographics, drug names, total tablet quantity consumed and alcohol involvement.. Gabapentinoids were involved in 2115 (2.9%) of the 72,391 IDOs recorded. Presentations involving a gabapentinoid increased proportionally from 0.5% in 2007 to 5.5% in 2015. The majority of IDOs involving a gabapentinoid were made by females (59.9%), with over one-third (37.2%) involving alcohol. Compared with IDOs involving other drugs, presentations with a gabapentinoid were made by persons who were older (median 37 vs. 32 years) and involved a significantly greater median quantity of tablets (30 vs. 21, p ≤ 0.001), with over one-quarter (27.4%) of these involving the ingestion of 50 tablets or more. Admission to hospital was significantly more common following IDOs with a gabapentinoid compared with those without (49.4% vs. 41.4%, p ≤ 0.001).. This study identified the increasing use of gabapentinoids in IDO, describing the profile and overdose characteristics of presentations. It is important for clinicians to exercise vigilance while prescribing gabapentinoids, including being aware of other medications that their patients may have access to. Our findings support the need for routine monitoring for signs of misuse among those prescribed gabapentinoids.

Topics: Adult; Alcohol Drinking; Amines; Cyclohexanecarboxylic Acids; Drug Overdose; Emergency Service, Hospital; Female; Gabapentin; gamma-Aminobutyric Acid; Hospitalization; Humans; Ireland; Male; Middle Aged; Pregabalin; Registries; Young Adult

Topics: Adult; Analgesics; Analgesics, Opioid; Case-Control Studies; Chronic Pain; Drug Interactions; Drug Overdose; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Ontario; Pregabalin; Risk Factors

Use of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment.. This retrospective register-based open cohort study included nation-wide register data including all individuals who were dispensed methadone or buprenorphine as opioid maintenance treatment for opioid dependence between July, 2005 and December, 2012 (N=4501). Outcome variables were overdose mortality and non-overdose mortality, respectively. Extended Cox regression analyses examined associations between type of sedative prescriptions and death, controlling for sex, age, previous overdoses and suicide attempts, psychiatric in-patient treatment and opioid maintenance treatment status. Opioid maintenance was assumed to last for 90days (or 30days in a sensitivity analysis) after the last methadone or buprenorphine prescription.. Benzodiazepine prescriptions were associated with non-overdose death (HR: 2.02, 95% CI: 1.29-3.18) but not significantly associated with overdose death (1.49, 0.97-2.29). Z-drug (1.60, 1.07-2.39) and pregabalin prescriptions (2.82, 1.79-4.43) were associated with overdose death. In the sensitivity analysis, all categories of sedatives, including benzodiazepines, were significantly associated with overdose death.. Caution is advised when prescribing sedative drugs, including benzodiazepines, z-drugs and pregabalin, to patients in opioid maintenance treatment.

Topics: Adolescent; Adult; Benzodiazepines; Buprenorphine; Drug Overdose; Drug Prescriptions; Female; Humans; Hypnotics and Sedatives; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pregabalin; Registries; Retrospective Studies; Young Adult

To examine the risk to heroin users of also using gabapentin or pregabalin (gabapentoids).. Multi-disciplinary study: we (a) examined trends in drug-related deaths and gabapentoid prescription data in England and Wales to test for evidence that any increase in deaths mentioning gabapentin or pregabalin is associated with trends in gabapentoid prescribing and is concomitant with opioid use; (b) interviewed people with a history of heroin use about their polydrug use involving gabapentin and pregabalin; and (c) studied the respiratory depressant effects of pregabalin in the absence and presence of morphine in mice to determine whether concomitant exposure increased the degree of respiratory depression observed.. England and Wales.. Interviews were conducted with 30 participants (19 males, 11 female).. (a) Office of National Statistics drug-related deaths from 1 January 2004 to 31 December 2015 that mention both an opioid and pregabalin or gabapentin; (b) subjective views on the availability, use, interactions and effects of polydrug use involving pregabalin and gabapentin; and (c) rate and depth of respiration.. Pregabalin and gabapentin prescriptions increased approximately 24% per year from 1 million in 2004 to 10.5 million in 2015. The number of deaths involving gabapentoids increased from fewer than one per year prior to 2009 to 137 in 2015; 79% of these deaths also involved opioids. The increase in deaths was correlated highly with the increase in prescribing (correlation coefficient 0.94; 5% increase in deaths per 100 000 increase in prescriptions). Heroin users described pregabalin as easy to obtain. They suggested that the combination of heroin and pregabalin reinforced the effects of heroin but were concerned it induced 'blackouts' and increased the risk of overdose. In mice, a low dose of S-pregabalin (20 mg/kg) that did not itself depress respiration reversed tolerance to morphine depression of respiration (resulting in 35% depression of respiration, P < 0.05), whereas a high dose of S-pregabalin (200 mg/kg) alone depressed respiration and this effect summated with that of morphine.. For heroin users, the combination of opioids with gabapentin or pregabalin potentially increases the risk of acute overdose death through either reversal of tolerance or an additive effect of the drugs to depress respiration.

Topics: Adult; Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Interactions; Drug Overdose; Drug Users; England; Female; Gabapentin; gamma-Aminobutyric Acid; Heroin Dependence; Humans; Male; Mice; Middle Aged; Pregabalin; Risk; Wales; Young Adult

Topics: Adult; Anti-Anxiety Agents; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Female; GABA Agents; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Pregabalin; Self Report; Substance Abuse Detection; Switzerland

Pregabalin is a drug for treating epilepsy, anxiety disorders and neuropathic pain. Cases of poisoning are rare, though some have been fatal. Concentrations of pregabalin in postmortem human samples and its distribution have very rarely been documented. As the literature is so scarce, we propose to report the concentrations in autopsy samples of 18 people who had been taking Lyrica(®), including one case of a mixed overdose involving pregabalin. Analysis was carried out using an original Hydrophilic Interaction LIquid Chromatography (HILIC) technique coupled with a high-resolution mass spectrometer (m/z 160.1334 ± 5 ppm). The sensitivity of the technique enables a quick and simple treatment of the samples by protein precipitation. The method was validated in the whole blood with detection and quantification limits of 0.025 and 0.060 µg/mL, respectively. Pregabalin was a likely factor in the cause of death in 3 of the 18 cases. In the other individuals, the concentrations ranged from 0.4 to 17.0 in the peripheral blood, 1.5 to 11.1 in the central blood, 126.6 to 2004.6 in the urine and 10.5 to 58.3 µg/mL in the bile, with median values of 5.6, 4.6, 534.6 and 17.7, respectively.

Topics: Adult; Aged; Aged, 80 and over; Autopsy; Chromatography, High Pressure Liquid; Drug Overdose; Female; gamma-Aminobutyric Acid; Humans; Hydrophobic and Hydrophilic Interactions; Male; Mass Spectrometry; Middle Aged; Pregabalin; Reproducibility of Results

Topics: Amines; Analgesics; Anti-Anxiety Agents; Cyclohexanecarboxylic Acids; Drug Overdose; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Iatrogenic Disease; Male; Practice Patterns, Physicians'; Pregabalin; Prescription Drug Misuse; Prescription Drugs; United States

Patient-controlled analgesia (PCA) is an established standard therapy for providing postoperative analgesia. To avoid possible abuse by patients each PCA pump is secured by a pin code that should be neither known nor accessible to patients. The two case reports described illustrate how manipulation of a PCA pump led to massive opioid abuse by the patients who decoded the pin code for unlimited additional doses. One patient developed withdrawal symptoms after switching the therapy and, as a consequence even had to be admitted to the intensive care unit (ICU). Easy access to the PCA pump codes on the internet for the patients and the impossibility of changing the pin codes by the medical staff played an important role in these two cases.

Topics: Adolescent; Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Codeine; Critical Care; Drug Overdose; Electronic Data Processing; Female; gamma-Aminobutyric Acid; Humans; Internet; Male; Opioid-Related Disorders; Pain, Postoperative; Physicians; Pregabalin; Wounds, Gunshot

There are two previously reported cases describing the management of pregabalin self-poisoning and one further case of management of therapeutic pregabalin accumulation. The peak reported pregabalin concentrations in these cases ranged from 13 mg/L to approximately 60 mg/L. Previous case reports have suggested that both supportive care and enhanced elimination are appropriate managements for pregabalin toxicity. A 54-year-old male presented following ingestion of 8.4 g of pregabalin. Initially, he had no clinical features of toxicity, although he developed significant neurological depression and coma approximately 3 h post-ingestion. He was managed with supportive care (including endotracheal intubation and mechanical ventilation) until his level of consciousness improved. Subsequent toxicological screening confirmed isolated pregabalin ingestion, with a serum pregabalin concentration of 66.5 mg/L at the time he clinically deteriorated. The pharmacokinetic properties of pregabalin indicate the potential value of extra-corporeal elimination methods such as haemodialysis. Clinical toxicologists should be aware that whilst there is a pharmacokinetic basis for the use of extra-corporeal methods in those with severe toxicity arising from excessive plasma pregabalin concentrations, there are case reports, including this one, where patients have been managed with supportive measures only.

Topics: Analgesics; Drug Overdose; gamma-Aminobutyric Acid; Humans; Intubation, Intratracheal; Male; Middle Aged; Neurotoxicity Syndromes; Palliative Care; Poisoning; Pregabalin; Respiration, Artificial

Topics: Anticonvulsants; Antidotes; Charcoal; Drug Overdose; Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Pregabalin; Sleep; Suicide, Attempted

We report a case of intentional overdose in a 29-year-old male with two of the newer anti-epileptic agents, lamotrigine and pregabalin. To our knowledge, this case report details the highest plasma levels of lamotrigine ever recorded in the literature. The patient presented with seizures and a reduced level of consciousness. Management of these and subsequent complications centres on supportive care in the high dependency and intensive therapy units.

Topics: Adult; Anticonvulsants; Drug Overdose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Pregabalin; Seizures; Suicide, Attempted; Triazines; Unconsciousness