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Gabapentina , Humanos , Gabapentina/efectos adversos , Gabapentina/uso terapéutico , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Ácido gamma-Aminobutírico/efectos adversos , Aminas/efectos adversos , Pregabalina/efectos adversos , Pregabalina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/efectos adversos , Dolor/tratamiento farmacológico , Dolor/inducido químicamenteRESUMEN
OBJECTIVE: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024. METHODOLOGY: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored. RESULTS: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489). CONCLUSION: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects. KEY WORDS: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.
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Fallo Renal Crónico , Pregabalina , Prurito , Diálisis Renal , Sertralina , Uremia , Humanos , Sertralina/uso terapéutico , Sertralina/administración & dosificación , Pregabalina/uso terapéutico , Femenino , Prurito/tratamiento farmacológico , Prurito/etiología , Masculino , Persona de Mediana Edad , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Adulto , Uremia/complicaciones , Uremia/terapia , Pakistán , Resultado del Tratamiento , AncianoRESUMEN
Over half of spinal cord injury (SCI) patients develop opioid-resistant chronic neuropathic pain. Safer alternatives to opioids for treatment of neuropathic pain are gabapentinoids (e.g., pregabalin and gabapentin). Clinically, gabapentinoids appear to amplify opioid effects, increasing analgesia and overdose-related adverse outcomes, but in vitro proof of this amplification and its mechanism are lacking. We previously showed that after SCI, sensitivity to opioids is reduced by fourfold to sixfold in rat sensory neurons. Here, we demonstrate that after injury, gabapentinoids restore normal sensitivity of opioid inhibition of cyclic AMP (cAMP) generation, while reducing nociceptor hyperexcitability by inhibiting voltage-gated calcium channels (VGCCs). Increasing intracellular Ca2+ or activation of L-type VGCCs (L-VGCCs) suffices to mimic SCI effects on opioid sensitivity, in a manner dependent on the activity of the Raf1 proto-oncogene, serine/threonine-protein kinase C-Raf, but independent of neuronal depolarization. Together, our results provide a mechanism for potentiation of opioid effects by gabapentinoids after injury, via reduction of calcium influx through L-VGCCs, and suggest that other inhibitors targeting these channels may similarly enhance opioid treatment of neuropathic pain.
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Analgésicos Opioides , AMP Cíclico , Gabapentina , Neuralgia , Transducción de Señal , Traumatismos de la Médula Espinal , Animales , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , AMP Cíclico/metabolismo , Ratas , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Analgésicos Opioides/farmacología , Gabapentina/farmacología , Transducción de Señal/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Canales de Calcio Tipo L/metabolismo , Calcio/metabolismo , Pregabalina/farmacología , Pregabalina/uso terapéutico , Sinergismo Farmacológico , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/efectos de los fármacosRESUMEN
Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.
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Neuropatías Diabéticas , Pregabalina , Ácido gamma-Aminobutírico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neuropatías Diabéticas/tratamiento farmacológico , Método Doble Ciego , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/efectos adversos , China , Pregabalina/uso terapéutico , Anciano , Adulto , Analgésicos/uso terapéutico , Resultado del Tratamiento , Dimensión del Dolor , Pueblos del Este de AsiaRESUMEN
RATIONALE: Diabetic neuropathy is a prevalent and debilitating complication of diabetes, necessitating effective pain management strategies. While pharmacological treatments, including opioids, are commonly employed, they pose significant challenges due to the risk of developing opioid-induced hyperalgesia (OIH). This case report aims to illustrate the efficacy of a comprehensive, multidisciplinary approach in managing painful diabetic neuropathy complicated by OIH. PATIENT CONCERNS: A 64-year-old male patient presented to the Pain Treatment Clinic with severe lower limb pain due to diabetic polyneuropathy. He had a history of multiple comorbidities. DIAGNOSES: The patient's condition and physical examination suggested the presence of opioid-induced hyperalgesia (OIH). Despite the increased dose of opioids, the patient did not report significant constipation or breathing difficulties but experienced drowsiness and dry mouth. A diagnosis of opioid and benzodiazepine dependence was made. INTERVENTIONS: The treatment plan involved the initiation of pregabalin and duloxetine, gradual reduction of opioid use, and psychiatric support for addiction management. OUTCOMES: Over 12 months, the patient experienced significant pain reduction and minimal adverse effects. LESSONS: Effective management of OIH involves gradual opioid tapering and a multimodal therapeutic approach. However, the optimal treatment strategies and the frequency of OIH occurrence remain areas of uncertainty, relying heavily on clinical expertise and individualized patient care. Further research is needed to refine these treatment strategies and improve patient outcomes.
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Analgésicos Opioides , Neuropatías Diabéticas , Hiperalgesia , Humanos , Masculino , Persona de Mediana Edad , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/terapia , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Manejo del Dolor/métodos , Clorhidrato de Duloxetina/uso terapéutico , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Terapia CombinadaRESUMEN
INTRODUCTION: In recent years, pregabalin has received growing attention due to its abuse liability. The aim of this study was to further characterize patterns of pregabalin users from substance abuse treatment facilities and detect changes in users profile over the study period. METHODS: The data source was the Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse (OPPIDUM) program, an annual, repeated, cross-sectional, nationwide, multicenter survey that collects consumption data from patients with substance use disorders. First, we described the characteristics of pregabalin users and their consumption patterns. We compared these data between 2008 and 2018 (P1) and 2019 and 2022 (P2). Second, we conducted a multiple correspondence analysis to identify profiles of users. RESULTS: From 2008 to 2022, 291 pregabalin users (0.37% of all users) from 116 substance abuse treatment facilities were identified. The number of pregabalin users was lower than 15 per year in P1 (n = 89) and between 40 and 60 per year in P2 (n = 202). The number of users who reported pregabalin as the first substance leading to dependence increased significantly in P2 compared with P1 (p < 0.005). When comparing P2 with P1, there was a significant increase in precarity (p < 0.001), users in prison (p = 0.002), withdrawal symptoms (p < 0.001), dependence (p < 0.001), use of higher dose of pregabalin (p = 0.029), and acquisition by deal/street market (p < 0.001). The multiple correspondence analysis allowed for the identification of distinct profiles of pregabalin users: (i) a cluster with mainly users from P1, who presented a simple use of pregabalin, and were older (> 45 years), were involved in opioid agonist treatment (OAT), and obtained pregabalin legally; and (ii) a cluster with mainly users from P2, who presented pregabalin dependence, and were younger (< 26 years), reported pregabalin as the first substance leading to dependence, used doses higher than the market authorization, were in severe precarity, and were in prison. CONCLUSIONS: These data showed that the profile of pregabalin users has changed in the last years. Pregabalin use disorders also affect users without history of addiction.
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Pregabalina , Centros de Tratamiento de Abuso de Sustancias , Trastornos Relacionados con Sustancias , Pregabalina/uso terapéutico , Humanos , Masculino , Femenino , Adulto , Estudios Transversales , Trastornos Relacionados con Sustancias/epidemiología , Francia , Persona de Mediana Edad , Centros de Tratamiento de Abuso de Sustancias/estadística & datos numéricos , Adulto Joven , AdolescenteRESUMEN
INTRODUCTION: Acquired reactive perforating collagenosis (ARPC) is a rare perforating skin disease with unclear pathogenesis, often leading to misdiagnosis. Utilizing noninvasive skin microscopy improves diagnostic accuracy while reducing misdiagnosis rates. PATIENT CONCERNS: Given its association with systemic diseases, comprehensive examinations are crucial for early detection of related diseases such as tumors. Clinically, it still lacks standardized guidelines for the treatment. Clinical treatment is mostly based on symptomatic treatment. Oral administration of pregabalin capsules can significantly relieve itching symptoms, and narrow-wave ultraviolet irradiation can accelerate the recovery of skin lesions. DIAGNOSIS: Dermoscopy and skin biopsy was used to confirm this case was ARPC. INTERVENTIONS: Treatment was based on oral administration of 20 mg prednisone, 1 tablet of loratadine, 1 tablet of pregabalin in the morning and evening, and external application of halomethasone ointment. OUTCOMES: Itching symptoms were significantly relieved. CONCLUSION: This case report demonstrates that clinical dermoscopy can improve the diagnosis rate of ARPC, and pregabalin capsules can significantly relieve itching symptoms.
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Enfermedades del Colágeno , Humanos , Enfermedades del Colágeno/diagnóstico , Enfermedades del Colágeno/patología , Prurito/etiología , Prurito/tratamiento farmacológico , Pregabalina/uso terapéutico , Dermoscopía/métodos , Femenino , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/tratamiento farmacológico , Masculino , Piel/patología , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. MATERIALS AND METHODS: In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients' satisfaction. RESULTS: No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). CONCLUSIONS: The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.
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Acetaminofén , Dolor Agudo , Pregabalina , Tomografía Computarizada por Rayos X , Tramadol , Humanos , Tramadol/administración & dosificación , Tramadol/uso terapéutico , Tramadol/efectos adversos , Pregabalina/uso terapéutico , Pregabalina/administración & dosificación , Pregabalina/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Acetaminofén/efectos adversos , Dolor Agudo/tratamiento farmacológico , Dolor Agudo/etiología , Dolor Agudo/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Anciano , Quimioterapia Combinada , Adulto , Neoplasias Pulmonares/tratamiento farmacológico , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Punciones/efectos adversos , Punciones/métodos , Resultado del Tratamiento , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Manejo del Dolor/métodos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/tratamiento farmacológico , Nódulo Pulmonar Solitario/patología , Dimensión del DolorRESUMEN
The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.
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Modelos Animales de Enfermedad , Electroencefalografía , Lacosamida , Fármacos Neuroprotectores , Pregabalina , Topiramato , Animales , Lacosamida/farmacología , Lacosamida/uso terapéutico , Topiramato/farmacología , Topiramato/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Masculino , Pregabalina/farmacología , Pregabalina/uso terapéutico , Ratas , Conducta Animal/efectos de los fármacos , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Hipocampo/patología , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/inducido químicamente , Estado Epiléptico/fisiopatología , Ratas Wistar , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/inducido químicamenteRESUMEN
BACKGROUND: Painful diabetic peripheral neuropathy is one of the frequent presenting complaints in diabetes and endocrine clinics. Our main objective was to compare effectiveness of three commonly prescribed drugs: amitriptyline, pregabalin and duloxetine for treatment of painful diabetic peripheral neuropathy. METHODS: This was a comparative, prospective, observational study conducted among 99 diabetic patients with painful diabetic peripheral neuropathy having numeric rating pain scale ≥ 4. Thirty-three patients in each group were consecutively prescribed amitriptyline, pregabalin and duloxetine in lower dose (10mg/75mg/20mg) for first two weeks to gradually up titrate to higher dose (25mg/150mg/30mg) as per pain response for total duration of eight weeks. RESULTS: At the end of eight weeks, 84.9% in amitriptyline, 78.7% in pregabalin and 60.6% in duloxetine group had adequate pain reduction in form of mild or no pain. Among total patients, 42.5% patients had severe pain at baseline that decreased to 5% by the end of our study. Out of three drugs, 45.5% patients in amitriptyline group had complete resolution of pain as compared to 24.2% in pregabalin and 18.2% in duloxetine group (p value 0.05). Drowsiness (42.4%), dizziness (21.2%) and dry mouth (21.2%) were the commonest side effects among total participants in our study. CONCLUSIONS: Amitriptyline, pregabalin and duloxetine were all associated with adequate pain reduction among patients of painful diabetic peripheral neuropathy in our study, however, amitriptyline had more favorable findings with tolerable side effects.
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Amitriptilina , Analgésicos , Neuropatías Diabéticas , Clorhidrato de Duloxetina , Pregabalina , Humanos , Clorhidrato de Duloxetina/uso terapéutico , Pregabalina/uso terapéutico , Amitriptilina/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Analgésicos/uso terapéutico , Anciano , Adulto , Dimensión del DolorRESUMEN
AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.
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Analgésicos , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuralgia , Pregabalina , Humanos , Pregabalina/administración & dosificación , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Neuropatías Diabéticas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Anciano , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Neuralgia/tratamiento farmacológico , Resultado del Tratamiento , Dimensión del Dolor , Adulto , Esquema de Medicación , Satisfacción del PacienteRESUMEN
OBJECTIVE: Fibromyalgia, a chronic pain disorder, impacts approximately 2% of adults in the US. Gabapentin and pregabalin are common treatments to manage fibromyalgia-related pain. Our recent study showed the risk of adverse cardiovascular events increased in diabetic neuropathy patients who were prescribed gabapentin or pregabalin. Here, we investigated whether the prescription of gabapentin or pregabalin has similar cardiovascular risk in patients with fibromyalgia. METHODS: This retrospective cohort study leveraged electronic health records from 64 US healthcare organizations with 112 million patients. The study population included 105,602 patients first diagnosed with fibromyalgia and followed by a prescription of gabapentin, pregabalin, or other FDA-approved drugs for treating fibromyalgia from 2010 to 2019. Outcomes were deep venous thrombosis (DVT), myocardial infarcts (MI), peripheral vascular disease (PVD), strokes, heart failure, and pulmonary embolism (PE). In propensity-score-matched cohorts, 1-year and 5-year hazard ratios (HRs) were computed with their respective 95% confidence intervals (CIs). Additionally, we conducted sensitivity analyses on the subpopulations without other possible indications. RESULTS: For 5-year follow-up, gabapentin increased the risk of PVD (HR = 1.46, 95% CI = 1.17-1.80), MI (HR = 1.31, 95% CI = 1.03-1.66), heart failure (HR = 1.27, 95% CI = 1.10-1.48), DVT (HR = 1.80, 95% CI = 1.33-2.44), and PE (HR = 2.23, 95% CI = 1.62-3.07). Pregabalin increased the risk of DVT (HR = 1.49, 95% CI = 1.01-2.20), and PE (HR = 2.24, 95% CI = 1.43-3.50). For 1-year follow-up, gabapentin increased the risk of PVD (HR = 1.32, 95% CI = 1.11-1.57), DVT (HR = 1.35, 95% CI = 1.09-1.68), and PE (HR = 1.36, 95% CI = 1.17-1.57). Pregabalin increased the risk of PVD (HR = 1.32, 95% CI = 1.06-1.63) and PE (HR = 1.25, 95% CI = 1.03-1.52). Sensitivity analyses showed similar trends. CONCLUSION: In fibromyalgia patients, the prescription of gabapentin and pregabalin moderately increased the risk of several adverse cardiovascular events. This risk, together with benefits and other adverse reactions, should be considered when prescribing these medications for fibromyalgia patients.
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Enfermedades Cardiovasculares , Fibromialgia , Gabapentina , Pregabalina , Humanos , Fibromialgia/tratamiento farmacológico , Fibromialgia/complicaciones , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Gabapentina/uso terapéutico , Gabapentina/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/complicaciones , Anciano , Analgésicos/uso terapéutico , Analgésicos/efectos adversosRESUMEN
INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
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Estudios Cruzados , Quimioterapia Combinada , Fibromialgia , Melatonina , Pregabalina , Humanos , Fibromialgia/tratamiento farmacológico , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Pregabalina/uso terapéutico , Pregabalina/administración & dosificación , Método Doble Ciego , Adulto , Analgésicos/uso terapéutico , Analgésicos/administración & dosificación , Femenino , Persona de Mediana Edad , Manejo del Dolor/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Dimensión del Dolor , Dolor Crónico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic. MATERIALS/METHODS: We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events. RESULTS: For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I2=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I2=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed. CONCLUSION: There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future. PROSPERO REGISTRATION NUMBER: CRD42022361193.
Asunto(s)
Antineoplásicos , Gabapentina , Enfermedades del Sistema Nervioso Periférico , Pregabalina , Humanos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Gabapentina/uso terapéutico , Gabapentina/efectos adversos , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.
Asunto(s)
Amitriptilina , Quimioterapia Combinada , Ketamina , Lidocaína , Pregabalina , Prurito , Centros de Atención Terciaria , Humanos , Estudios Retrospectivos , Prurito/tratamiento farmacológico , Prurito/etiología , Femenino , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Amitriptilina/uso terapéutico , Amitriptilina/efectos adversos , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Ketamina/uso terapéutico , Ketamina/efectos adversos , Ketamina/administración & dosificación , Pregabalina/uso terapéutico , Anciano , Adulto , Antipruriginosos/uso terapéutico , Antipruriginosos/efectos adversos , Florida , Crema para la Piel , Administración Cutánea , Registros Electrónicos de SaludRESUMEN
BACKGROUND: Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids, multimodal analgesia, which involves the use of drugs of different classes, may be utilized. One of the drugs under consideration is pregabalin. Despite an opioid-sparing potential, few studies assess the role of pregabalin as an element of multimodal analgesia in LSG. Considering the limited number and inconsistent results of available studies, we decided to conduct a randomized, prospective study on the effect of preemptive pregabalin administration in obese patients on opioid consumption, pain scores, the incidence of opioid side effects, and hemodynamical stability. METHODS: The study is designed as a prospective randomized controlled trial with double-blinding. Randomization will be performed in a block with a parallel 1:1 allocation. The intervention will involve receiving a pregabalin 150 mg capsule 1-2 h before the surgery, whereas the control group will receive an identically looking placebo. The primary outcome measure will be total oxycodone consumption in the first 24 h following surgery. Secondary outcome measures will be pain severity assessed using the Numerical Rating Scale (NRS) 1, 6, 12, and 24 h after surgery, postoperative sedation on the Ramsay scale, PONV impact scale, the incidence of desaturation episodes < 94%, and episodes of blurred vision at 1, 6, 12, and 24 h after surgery, intraoperative hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), total fluid volume, and total ephedrine dose. Patient comfort will be additionally assessed using the QoR-40 questionnaire at discharge. DISCUSSION: The study will explore the efficacy and safety of preemptive pregabalin in a dose of 150 mg as a co-analgesic used in multimodal analgesia for LSG. As studies on opioid-sparing regimes concern the safety of obese patients, we aim to contribute objective data with a relatively large study sample size. The result of the present clinical trial may support the reassessment of recommendations to use pregabalin in the studied population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05804591. Registered on 07.04.2023.
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Analgésicos Opioides , Gastrectomía , Hemodinámica , Laparoscopía , Dolor Postoperatorio , Pregabalina , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Pregabalina/administración & dosificación , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Método Doble Ciego , Estudios Prospectivos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Gastrectomía/efectos adversos , Gastrectomía/métodos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Laparoscopía/efectos adversos , Hemodinámica/efectos de los fármacos , Adulto , Resultado del Tratamiento , Dimensión del Dolor , Administración Oral , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Persona de Mediana Edad , Masculino , Factores de Tiempo , Femenino , Adulto Joven , Recuperación de la Función , Oxicodona/administración & dosificación , Oxicodona/efectos adversos , Oxicodona/uso terapéuticoAsunto(s)
Gabapentina , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Gabapentina/uso terapéutico , Gabapentina/efectos adversos , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/efectos adversos , Aminas/uso terapéutico , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Pregabalina/uso terapéutico , Pregabalina/efectos adversosRESUMEN
Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.
Asunto(s)
Analgésicos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Gabapentina , Inflamación , Nefopam , Neuralgia , Osteoartritis , Animales , Neuralgia/tratamiento farmacológico , Neuralgia/inducido químicamente , Nefopam/farmacología , Nefopam/uso terapéutico , Ratones , Gabapentina/farmacología , Gabapentina/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Osteoartritis/tratamiento farmacológico , Osteoartritis/inducido químicamente , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Pregabalina/farmacología , Pregabalina/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/inducido químicamente , CarrageninaRESUMEN
OBJECTIVE: Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN. PATIENTS AND METHODS: We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria. RESULTS: No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively). CONCLUSIONS: No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Asunto(s)
Amitriptilina , Analgésicos , Neuropatías Diabéticas , Pregabalina , Pregabalina/uso terapéutico , Pregabalina/efectos adversos , Pregabalina/administración & dosificación , Amitriptilina/uso terapéutico , Amitriptilina/efectos adversos , Humanos , Neuropatías Diabéticas/tratamiento farmacológico , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Calidad de VidaRESUMEN
This study investigated the effects of pregabalin on microglial differentiation in rats with neuropathic pain (NP) induced by sciatic nerve ligation and transection. After confirming NP, the rats were randomly allocated to either a pregabalin or control group. The pregabalin group received intraperitoneal injections of 10 mg/kg pregabalin, while the control group received an equivalent volume of normal saline following surgery. On postoperative day 28, neuronal damage, microglial activity, and microglial differentiation were assessed. The pregabalin group exhibited significantly less neuronal damage compared to the control group, along with a significant decrease in activated microglial expression in both the brain and spinal cord. Pregabalin treatment also significantly altered the microglial phenotype expression, with a decrease in the M1 phenotype percentage and an increase in the M2 phenotype percentage in both the brain (M1 phenotype: 43.52 ± 12.16% and 18.00 ± 8.57% in the control and pregabalin groups, respectively; difference: 27.26 [15.18-42.10], p = 0.002; M2 phenotype: 16.88 ± 6.47% and 39.63 ± 5.82% in the control and pregabalin groups, respectively; difference 22.04 [17.17-32.70], p < 0.001) and the spinal cord ipsilateral to nerve injury (M1 phenotype: 44.35 ± 12.12% and 13.78 ± 5.39% in the control and pregabalin groups, respectively; difference 30.46 [21.73-44.45], p < 0.001; M2 phenotype: 7.64 ± 3.91% and 33.66 ± 7.95% in the control and pregabalin groups, respectively; difference 27.41 [21.21-36.30], p < 0.001). Overall, pregabalin treatment significantly decreased the microglial M1 phenotype while increasing the microglial M2 phenotype in NP rats.