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1.
Postgrad Med ; 133(1): 1-9, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33423590

RESUMO

Pregabalin is one of the first-line treatments approved for the management of neuropathic pain (NeP). While many patients benefit from treatment with pregabalin, they are often treated with suboptimal doses, possibly due to unfamiliarity around prescribing the drug and/or side effects that can occur with up-titration. This narrative review discusses key aspects of initiating, titrating, and managing patients prescribed pregabalin therapy, and addresses concerns around driving and the potential for abuse, as well as when to seek specialist opinion. To ensure that patients derive maximum therapeutic benefit from the drug, we suggest a 'low and slow' dosing approach to limit common side effects and optimize tolerability alongside patients' expectations. When requiring titration to higher doses, we recommend initiating 'asymmetric dosing,' with the larger dose in the evening. Fully engaging patients in order for them to understand the expected timeline for efficacy and side effects (including their resolution), can also help determine the optimal titration tempo for each individual patient. The 'low and slow' approach also recognizes that patients with NeP are heterogeneous in terms of their optimal therapeutic dose of pregabalin. Hence, it is recommended that general practitioners closely monitor patients and up-titrate according to pain relief and side effects to limit suboptimal dosing or premature discontinuation.


Assuntos
Analgésicos/administração & dosagem , Neuralgia/tratamento farmacológico , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Fatores Etários , Analgésicos/uso terapêutico , Condução de Veículo , Comorbidade , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Adesão à Medicação , Medição da Dor , Educação de Pacientes como Assunto , Pregabalina/uso terapêutico , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
3.
Expert Opin Pharmacother ; 21(11): 1377-1387, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32511032

RESUMO

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Neuralgia/tratamento farmacológico , Administração Tópica , Analgésicos/efeitos adversos , Capsaicina/efeitos adversos , Análise Custo-Benefício , Prova Pericial , Humanos , Neuralgia/metabolismo , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Qualidade de Vida , Canais de Cátion TRPV/metabolismo , Adesivo Transdérmico
4.
Br J Anaesth ; 125(2): 159-167, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32571568

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Analgésicos Opioides/efeitos adversos , Benzodiazepinas/efeitos adversos , Overdose de Drogas/epidemiologia , Gabapentina/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Pregabalina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Escócia/epidemiologia , Fatores Sexuais , Adulto Jovem
6.
BMC Pharmacol Toxicol ; 21(1): 16, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111255

RESUMO

BACKGROUND: Pregabalin is an anticonvulsive, analgesic and anxiolytic medication. The typical side effects include dizziness, somnolence and weight gain. Few studies or case reports have demonstrated psychiatric side effects resulting from its use. CASE PRESENTATION: We present a patient who suffered visual hallucinations and agitation associated with an increase in pregabalin dose, resolving completely after pregabalin discontinuation. CONCLUSIONS: Acute visual hallucinations should be considered in the clinical spectrum of very rare side effects of pregabalin use, especially at higher doses. Tapered discontinuation of the medication can improve and resolve symptoms.


Assuntos
Acatisia Induzida por Medicamentos/etiologia , Analgésicos/efeitos adversos , Alucinações/induzido quimicamente , Pregabalina/efeitos adversos , Adulto , Feminino , Humanos
7.
Epilepsia ; 61(4): 617-626, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32189338

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month-<4 years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG). METHODS: This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72 hours) at baseline and over the last 3 days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14 mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (loge [24-hour seizure rate + 1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms. RESULTS: Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/kg/d (n = 28) resulted in a statistically significant 35% reduction of loge (24-hour seizure rate + 1) versus placebo (n = 53; P = .022), an effect that was not observed with pregabalin 7 mg/kg/d (n = 59; P = .461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14 mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity. SIGNIFICANCE: Pregabalin 14 mg/kg/d (but not 7 mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Pregabalina/administração & dosagem , Convulsões/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Quimioterapia Adjuvante/métodos , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada/métodos , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Pregabalina/efeitos adversos , Gravação em Vídeo
9.
Artigo em Russo | MEDLINE | ID: mdl-32105267

RESUMO

AIM: To study the efficacy of pregabalin for relapse prevention and reduction of drinking in patients with alcohol dependence. MATERIAL AND METHODS: One hundred recently detoxified out-patients with alcohol dependence were randomly assigned to one of two treatment groups. Patients of the first group (n=50; 38 men, 12 women, age 43.0±1.27) received pregabalin (150 mg once a day at night time) for 3 months, while patients of the second group (n=50; 45 men, 5 women, age 45.92±1.4) received identically looking placebo. All patients received standardized manualized weekly counseling (medical management). Drinking was measured on the weekly basis with Time Line Follow Back technique and GGT enzyme activity. Also, craving for alcohol, depression, and anxiety were measured weekly with the number of scales. RESULTS: Kaplan-Meier survival analysis demonstrated significantly higher retention in treatment and in remission in the pregabalin group (lower drop out and relapse rate) mediana (CL)-12 (10.4-13.6) weeks in the pregabalin group vs. 6 (4.5-7.5) in the placebo group, Log Rank Mantel-Cox test = 0.005). Proportion of patients, who completed treatment in the pregabalin group, was significantly higher compared to the placebo group: 50% vs. 24%. Mean duration of participation in the treatment program was also higher in the pregabalin group: 9.1±0.5 weeks vs. 7.1±0.5 in the placebo group. General linear model demonstrated the significant treatment group effect on: (1) total alcohol consumption (TAC) (mean grams of alcohol per day) with lower TAC in the pregabalin group and (2) on the number of heavy drinking days (NHDD) with lower NHDD in the pregabalin group. Mean NHDD per patient for the period of participation in the study was lower in the pregabalin group (3.6±0.7 vs. 6.4±0.8; p=0.009), while the mean number of abstinent (sober) days was higher (55.9±3.6 vs. 40.0±3.3; p=0.001). No significant differences between the two groups were found in the scores on craving for alcohol, depression and anxiety scales. GGT activity was also similar in both groups throughout the study with no significant between group differences. The rate of adverse events (sleepiness, dizziness, and headache) was insignificantly higher in the pregabalin group compared with the placebo group. All adverse events were mild, gradually disappeared, and did not require any medication. CONCLUSION: Results of this study provide evidence that pregabalin in a low dose of 150 mg per day is an effective and safe medication for relapse prevention and reduction of drinking in patients with alcohol dependence.


Assuntos
Alcoolismo/tratamento farmacológico , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Adulto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pregabalina/administração & dosagem , Indução de Remissão , Resultado do Tratamento
11.
Doc Ophthalmol ; 140(3): 279-287, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31900741

RESUMO

PURPOSE: Pregabalin binds to the α2-δ1/α2-δ2 subunits of the voltage-gated L-type calcium channel (LTCC), which is expressed in rod/cone photoreceptor terminals. The purpose of this report was to describe electroretinographic abnormalities associated with pregabalin treatment. CASE PRESENTATION: This is an observational case report. A 49-year-old female reported photophobia and night blindness in her left eye after 10 months of pregabalin administration. One month after the symptoms, ophthalmic examinations were performed, which revealed good visual acuity and no remarkable fundus findings. However, full-field electroretinography (ERG) of the left eye revealed a decreased b-wave in rod ERG, a slightly decreased a-wave and severely decreased b-wave (negative ERG) in bright flash ERG, decreased a- and b-waves in cone ERG, and decreased b-waves in 30-Hz flicker ERG. These findings are similar to those seen in incomplete congenital stationary night blindness, whereas the right eye ERG showed normal responses, except for a square a-wave in cone ERG. The ERG gradually improved from 1 to 12 months after discontinuing pregabalin. Finally, b-waves in bright flash ERG and cone ERG responses largely recovered, but b-waves in rod ERG and a-waves in bright flash ERG only partially recovered in the left eye. The square a-wave recovered to normal in the right eye. CONCLUSIONS: This is the first report to indicate that ERG abnormalities might be associated with pregabalin treatment. Our results suggest that pregabalin may affect LTCC function via the α2-δ1/α2-δ2 subunits, which leads to defective synaptic transmission from rod/cone photoreceptors to bipolar cells.


Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Eletrorretinografia/efeitos dos fármacos , Cegueira Noturna/induzido quimicamente , Fotofobia/induzido quimicamente , Pregabalina/efeitos adversos , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Canais de Cálcio Tipo L , Adaptação à Escuridão , Feminino , Humanos , Pessoa de Meia-Idade , Cegueira Noturna/fisiopatologia , Fotofobia/fisiopatologia , Acuidade Visual/fisiologia
12.
Drug Alcohol Depend ; 206: 107709, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732295

RESUMO

BACKGROUND: Although there have been increasing reports of intentional gabapentin misuse, epidemiological evidence for the phenomenon is limited. The purpose of this study was to determine whether there are pharmacovigilance abuse signals for gabapentin. METHODS: Using FDA Adverse Events Reporting System reports from January 1, 2005 to December 31, 2015, we calculated pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean) for abuse-related adverse event (AR-AE)-gabapentin pairs. Loglinear modeling assessed the frequency of concurrent reporting of abuse-related and abuse-specific AEs (AS-AEs) associated with gabapentin. Findings were compared to a positive (pregabalin) and negative (duloxetine) control. RESULTS: From 2005-2015 there were 5,951,229 unique AE reports submitted to the FDA including 99,977 for gabapentin, 73,977 for duloxetine, and 97,813 for pregabalin. Significant drug-AR-AE pair signals involving gabapentin included: drug abuser, multiple drug overdose, and substance-induced psychotic disorder. Significant drug AR-AE signals involving gabapentin and pregabalin, but not duloxetine, were: ataxia, dependence, drug abuse, increased drug tolerance, and overdose. Compared to duloxetine, gabapentin had significantly greater odds of a co-report for an AS-AE with drug withdrawal syndrome (OR: 6.55), auditory hallucinations (OR: 4.57), delusions (OR: 2.36), euphoric mood (OR: 5.45), ataxia (OR: 2.85), drug abuser (OR: 3.01), aggression (OR: 1.98), psychotic disorder (OR: 1.96), and feeling abnormal (OR: 1.31). CONCLUSIONS: We identified abuse-related signals for gabapentin and highlighted several CNS effects that may be associated with its abuse. Gabapentin prescribers should be aware of the drug's abuse liability and effects that may accompany its use.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Gabapentina/efeitos adversos , Farmacovigilância , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , United States Food and Drug Administration/estatística & dados numéricos , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Teorema de Bayes , Bases de Dados Factuais , Cloridrato de Duloxetina/efeitos adversos , Humanos , Pregabalina/efeitos adversos , Fatores de Risco , Estados Unidos/epidemiologia
13.
Int J Colorectal Dis ; 35(2): 323-331, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31863206

RESUMO

PURPOSE: In order to reduce postoperative opioid administration and pain levels in patients submitted to laparoscopic colectomy, we assessed the efficacy of preemptive use of pregabalin (PG), as part of a multimodal analgesia scheme, in a randomized controlled trial setting. METHODS: Overall, fifty adult patients scheduled for elective laparoscopic colectomy were included and randomized in our trial. In the experimental group, 23 patients received preoperatively 2 doses of 150 mg PG per os, whereas the control group consisted of 27 cases, where a matching to PG placebo was administered at the same scheme. The two groups had identical analgesia and anesthesia regimens otherwise. Our study endpoints included postoperative morphine consumption, postoperative pain, and complication rates. RESULTS: Patients in the PG group displayed a significantly reduced morphine consumption at 8 h, 24 h, and 48 h postoperatively. The two groups were comparable in terms of postoperative pain (rest and movement assessment) and side effects. CONCLUSIONS: The preoperative addition of PG resulted in a significant reduction of the postoperative opioid consumption in patients undergoing laparoscopic colectomy. However, an association with the postoperative pain scores was not identified.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos/administração & dosagem , Colectomia/efeitos adversos , Laparoscopia/efeitos adversos , Morfina/administração & dosagem , Manejo da Dor , Dor Pós-Operatória/prevenção & controle , Pregabalina/administração & dosagem , Pré-Medicação , Idoso , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Esquema de Medicação , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Manejo da Dor/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Pregabalina/efeitos adversos , Pré-Medicação/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Am J Emerg Med ; 38(4): 852.e1-852.e2, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31883652

RESUMO

Priapism is defined as a prolonged erection of the penis for at least 4 h without sexual stimulation. It may occur in all age groups. Drugs are the most common cause in adults. A 64-year-old male patient was admitted to the emergency department with painful erection that had lasted for 2 days without sexual stimulation. Our patient had used pregabalin for around 1 year due to neuropathic pain. The dose of the drug was increased as his pain scaled up recently. Approximately 30 cc of dark blood was drained from the corpus cavernosum with an 18 Gauge needle in the emergency department. Cavernous blood aspiration and irrigation resulted in significant recovery and relief. We present this report of priapism associated with pregabalin as it is a rare case with insufficient number of studies in the literature.


Assuntos
Pregabalina/efeitos adversos , Priapismo/induzido quimicamente , Serviço Hospitalar de Emergência , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Pregabalina/uso terapêutico , Priapismo/terapia
15.
J Bone Joint Surg Am ; 102(3): 221-229, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804238

RESUMO

BACKGROUND: Gabapentinoids are commonly prescribed in perioperative multimodal analgesia protocols. Despite widespread use, the optimal dose to reduce opioid consumption while minimizing risks is unknown. We assessed dose-dependent effects of gabapentinoids on opioid consumption and postoperative pulmonary complications following total hip or knee arthroplasty (THA or TKA). We hypothesized that use of a gabapentinoid on the day of THA or TKA is associated with an increased risk of postoperative pulmonary complications in a dose-response fashion compared with the risk for patients who did not receive the drug. METHODS: Using the Premier Database, we identified adults who underwent elective primary THA or TKA from 2009 to 2014. The exposure was receipt of a gabapentinoid (gabapentin or pregabalin) on the day of surgery. Gabapentin dose was categorized into 5 groups: none, 1 to 350, 351 to 700, 701 to 1,050, and >1,050 mg per day. Pregabalin dose was categorized into 4 groups: none, 1 to 110, 111 to 250, and >250 mg per day. The primary outcome was a composite of postoperative pulmonary complications, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, noninvasive ventilation, or invasive mechanical ventilation. RESULTS: Of 858,306 patients who underwent THA or TKA, 11.0% received gabapentin and 10.2% received pregabalin. The mean age (and standard deviation) of the patients was 65.6 ± 10.7 years, 39.6% were male, 78.2% were Caucasian, and 55.2% were covered by Medicare. In multilevel regression analysis, receipt of gabapentinoid at any dose on the day of surgery was associated with increased odds of postoperative pulmonary complications. Compared with no exposure to the drug being used by the particular group, all dose ranges of gabapentin and pregabalin were associated with greater odds of postoperative pulmonary complications (odds ratio, 95% confidence interval = 1.51, 1.40 to 1.63, for >1,050 mg of gabapentin and 1.81, 1.57 to 2.09, for >250 mg of pregabalin). We found no clinically meaningful associations between exposure to either gabapentin or pregabalin and perioperative opioid consumption or the length of the hospital stay. CONCLUSIONS: Exposure to gabapentinoids at any dose on the day of THA or TKA was associated with increased odds of postoperative pulmonary complications in a dose-response fashion, with minimal effects on perioperative opioid consumption. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Analgésicos/efeitos adversos , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Gabapentina/efeitos adversos , Pneumopatias/induzido quimicamente , Complicações Pós-Operatórias/induzido quimicamente , Pregabalina/efeitos adversos , Adulto , Idoso , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia do Joelho/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Estados Unidos
17.
Sci Rep ; 9(1): 15136, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641170

RESUMO

Drug addiction remains a prevalent and fatal disease worldwide that carries significant social and economic impacts. Recent reports suggest illicit pregabalin (Lyrica) use may be increasing among youth, however the addictive potential of pregabalin has not been well established. Drug seeking behavior and chronic drug use are associated with deficits in glutamate clearance and activation of postsynaptic glutamatergic receptors. In the current study, we investigated the abuse potential of pregabalin using conditioned place preference (CPP) paradigm. Different doses of pregabalin (30, 60, 90, and 120 mg/kg) were used to assess the seeking behavior in mice. Glutamate homeostasis is maintained by glutamate transporter type-1 (GLT-1), which plays a vital role in clearing the released glutamate from synapses and drug seeking behavior. Therefore, we investigated the role of glutamate in pregabalin-seeking behavior with ceftriaxone (CEF), a potent GLT-1 upregulator. Mice treated with pregabalin 60 and 90 mg/kg doses demonstrated drug seeking-like behavior, which was significantly blocked by CEF pretreatment. These results suggest that pregabalin-induced CPP was successfully modulated by CEF which could serve as a lead compound for developing treatment for pregabalin abuse.


Assuntos
Ácido Glutâmico/metabolismo , Pregabalina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Animais , Condicionamento Clássico , Masculino , Camundongos Endogâmicos BALB C , Fatores de Tempo
18.
Lancet Psychiatry ; 6(11): 935-950, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31588045

RESUMO

BACKGROUND: Antidepressants, opioids for non-cancer pain, gabapentinoids (gabapentin and pregabalin), benzodiazepines, and Z-drugs (zopiclone, zaleplon, and zolpidem) are commonly prescribed medicine classes associated with a risk of dependence or withdrawal. We aimed to review the evidence for these harms and estimate the prevalence of dispensed prescriptions, their geographical distribution, and duration of continuous receipt using all patient-linked prescription data in England. METHODS: This was a mixed-methods public health review, comprising a rapid evidence assessment of articles (Jan 1, 2008, to Oct 3, 2018; with searches of MEDLINE, Embase, and PsycINFO, and the Cochrane and King's Fund libraries), an open call-for-evidence on patient experience and service evaluations, and a retrospective, patient-linked analysis of the National Health Service (NHS) Business Services Authority prescription database (April 1, 2015, to March 30, 2018) for all adults aged 18 years and over. Indirectly (sex and age) standardised rates (ISRs) were computed for all 195 NHS Clinical Commissioning Groups in England, containing 7821 general practices for the geographical analysis. We used publicly available mid-year (June 30) data on the resident adult population and investigated deprivation using the English Indices of Multiple Deprivation (IMD) quintiles (quintile 1 least deprived, quintile 5 most deprived), with each patient assigned to the IMD quintile score of their general practitioner's practice for each year. Statistical modelling (adjusted incident rate ratios [IRRs]) of the number of patients who had a prescription dispensed for each medicine class, and the number of patients in receipt of a prescription for at least 12 months, was done by sex, age group, and IMD quintile. FINDINGS: 77 articles on the five medicine classes were identified from the literature search and call-for-evidence. 17 randomised placebo-controlled trials (6729 participants) reported antidepressant-associated withdrawal symptoms. Almost all studies were rated of very low, low, or moderate quality. The focus of qualitative and other reports was on patients' experiences of long-term antidepressant use, and typically sudden onset, severe, and protracted withdrawal symptoms when medication was stopped. Between April 1, 2017, and March 31, 2018, 11·53 million individuals (26·3% of residents in England) had a prescription dispensed for at least one medicine class: antidepressants (7·26 million [16·6%]), opioids (5·61 million [12·8%]), gabapentinoids (1·46 million [3·3%]), benzodiazepines (1·35 million [3·1%]), and Z-drugs (0·99 million [2·3%]). For three of these medicine classes, more people had a prescription dispensed in areas of higher deprivation, with adjusted IRRs (referenced to quintile 1) ranging from 1·10 to 1·24 for antidepressants, 1·20 to 1·85 for opioids, and 1·21 to 1·85 for gabapentinoids across quintiles, and higher ISRs generally concentrated in the north and east of England. In contrast, the highest ISRs for benzodiazepines and Z-drugs were generally in the southwest, southeast, and east of England, with low ISRs in the north. Z-drugs were associated with increased deprivation, but only at the highest quintile (adjusted IRR 1·11 [95% CI 1·01-1·22]). For benzodiazepines, prescribing was reduced for people in quintiles 4 (0·90 [0·85-0·96]) and 5 (0·89 [0·82-0·97]). In March, 2018, for each of medicine class, about 50% of patients who had a prescription dispensed had done so continuously for at least 12 months, with the highest ISRs in the north and east. Long-term prescribing was associated with a gradient of increased deprivation. INTERPRETATION: In 1 year over a quarter of the adult population in England had a prescription dispensed for antidepressants, opioids (for non-cancer pain), gabapentinoids, benzodiazepines, or Z-drugs. Long-term (>12 months) prescribing is common, despite being either not recommended by clinical guidelines or of doubtful efficacy in many cases. Enhanced national and local monitoring, better guidance for personalised care, and better doctor-patient decision making are needed. FUNDING: Public Health England.


Assuntos
Analgésicos Opioides/efeitos adversos , Analgésicos/efeitos adversos , Antidepressivos/efeitos adversos , Benzodiazepinas/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Acetamidas/efeitos adversos , Adolescente , Adulto , Idoso , Compostos Azabicíclicos/efeitos adversos , Bases de Dados Factuais/estatística & dados numéricos , Inglaterra/epidemiologia , Feminino , Gabapentina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Pregabalina/efeitos adversos , Saúde Pública , Pirimidinas/efeitos adversos , Síndrome de Abstinência a Substâncias/epidemiologia , Adulto Jovem , Zolpidem/efeitos adversos
19.
BMJ Case Rep ; 12(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31604720

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe adverse drug reaction driven by eosinophilia. Treatment is focused on withdrawal of medication, supportive care and immunosuppression such as high-dose corticosteroid therapy. Here we report a 56-year-old male patient who initially presented with breathlessness and eosinophilia, subsequent development of respiratory failure and admission to ITU for non-invasive ventilation. The patient continued to deteriorate despite high-dose prednisolone and methylprednisolone. Other causes of hypereosinophilia were normal. He was diagnosed with DRESS syndrome secondary to pregabalin and was treated with subcutaneous mepolizumab. We observed the rapid resolution of eosinophilia and clinical improvement; the patient was discharged home within a month of administration. This represents the successful use of mepolizumab in the acute setting of pulmonary failure secondary to DRESS. A similar approach could be adopted in other acute conditions with refractory eosinophilic inflammation where standard steroid therapy has failed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/complicações , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina/efeitos adversos
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